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Benguella-Benmansour M, Boucherit K, Mesli N. Oxidant/Antioxidant Status in Patients with BCR-ABL1 Negative Myeloproliferative Neoplasms. Indian J Hematol Blood Transfus 2025; 41:23-30. [PMID: 39917514 PMCID: PMC11794732 DOI: 10.1007/s12288-024-01827-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Accepted: 07/23/2024] [Indexed: 02/09/2025] Open
Abstract
Excessive production of reactive oxygen species (ROS) leading to oxidative stress have been associated with many leukemias. In order to show whether there is a difference in ROS levels and total antioxidant power between BCR-ABL1 negative myeloproliferative neoplasms (MPNs) patients and controls, this study aims to evaluate the oxidant/antioxidant status in patients with MPN. 43 subjects with BCR-ABL1 negative MPNs and 40 healthy controls were included in this study. Oxidative stress was investigated by determination of total antioxidant power, catalase activity and concentrations of vitamins (A, C and E), malondialdehyde, hydroperoxides and carbonylated proteins. Oxygen Radical Absorbance Capacity (ORAC) was lower in BCR-ABL1 negative MPN patients compared with control group (0.40 ± 0.17 vs. 0.81 ± 0.06) AU (p˂0.01). Vitamins A (0.61 ± 0.19 vs. 0.82 ± 0.11) mol/L (p˂0.05), E (0.29 ± 0.08 vs. 1.10 ± 0.56) mol/L (p˂0.01) and C (19.22 ± 0,49 vs. 45.52 ± 0.36)µg/mL (p˂0.01) concentrations were lower in the same group compared to controls. No difference in catalase (CAT) activity between the BCR-ABL1 negative MPN and control groups was observed (p > 0.05). Higher malondialdehyde (MDA) plasma levels were found in BCR-ABL1 negative MPN patients compared to controls (2.97 ± 0.24 vs. 0.38 ± 0.18) mmol/L (p < 0.01). No significant differences were observed between BCR-ABL1 negative MPN and control groups in plasma hydroperoxide and carbonyl protein rates (p > 0.05; p > 0.05). BCR-ABL1 negative myeloproferative neoplasms are associated with dysregulation of redox balance of oxidant /antioxidant leading to an oxidative stress status.
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Affiliation(s)
- Meriem Benguella-Benmansour
- Laboratory Antibiotics antifungals, physicochemical, synthesis and biological activity, University of Tlemcen, Tlemcen, Algeria
| | - Kebir Boucherit
- Laboratory Antibiotics antifungals, physicochemical, synthesis and biological activity, University of Tlemcen, Tlemcen, Algeria
| | - Naima Mesli
- Department of Onco-Hematology, University-Hospital Center of Tlemcen, Tlemcen, Algeria
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Todor SB, Ichim C, Boicean A, Mihaila RG. Cardiovascular Risk in Philadelphia-Negative Myeloproliferative Neoplasms: Mechanisms and Implications-A Narrative Review. Curr Issues Mol Biol 2024; 46:8407-8423. [PMID: 39194713 DOI: 10.3390/cimb46080496] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Revised: 07/24/2024] [Accepted: 07/31/2024] [Indexed: 08/29/2024] Open
Abstract
Myeloproliferative neoplasms (MPNs), encompassing disorders like polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), are characterized by clonal hematopoiesis without the Philadelphia chromosome. The JAK2 V617F mutation is prevalent in PV, ET, and PMF, while mutations in MPL and CALR also play significant roles. These conditions predispose patients to thrombotic events, with PMF exhibiting the lowest survival among MPNs. Chronic inflammation, driven by cytokine release from aberrant leukocytes and platelets, amplifies cardiovascular risk through various mechanisms, including atherosclerosis and vascular remodeling. Additionally, MPN-related complications like pulmonary hypertension and cardiac fibrosis contribute to cardiovascular morbidity and mortality. This review consolidates recent research on MPNs' cardiovascular implications, emphasizing thrombotic risk, chronic inflammation, and vascular stiffness. Understanding these associations is crucial for developing targeted therapies and improving outcomes in MPN patients.
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Affiliation(s)
- Samuel Bogdan Todor
- Faculty of Medicine, Lucian Blaga University of Sibiu, 550169 Sibiu, Romania
| | - Cristian Ichim
- Faculty of Medicine, Lucian Blaga University of Sibiu, 550169 Sibiu, Romania
| | - Adrian Boicean
- Faculty of Medicine, Lucian Blaga University of Sibiu, 550169 Sibiu, Romania
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Găman MA, Srichawla BS, Chen YF, Roy P, Dhali A, Nahian A, Manan MR, Kipkorir V, Suteja RC, Simhachalam Kutikuppala LV, Găman AM, Diaconu CC. Overview of dyslipidemia and metabolic syndrome in myeloproliferative neoplasms. World J Clin Oncol 2024; 15:717-729. [PMID: 38946827 PMCID: PMC11212607 DOI: 10.5306/wjco.v15.i6.717] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Revised: 05/05/2024] [Accepted: 05/28/2024] [Indexed: 06/24/2024] Open
Abstract
Myeloproliferative neoplasms (MPNs) occur due to the abnormal proliferation of one or more terminal myeloid cell lines in peripheral blood. Subjects suffering from MPNs display a high burden of cardiovascular risk factors, and thrombotic events are often the cause of death in this population of patients. Herein, we provide a brief overview of dyslipidemia and metabolic syndrome and their epidemiology in MPNs and examine the common molecular mechanisms between dyslipidemia, metabolic syndrome, and MPNs, with a special focus on cardiovascular risk, atherosclerosis, and thrombotic events. Furthermore, we investigate the impact of dyslipidemia and metabolic syndrome on the occurrence and survival of thrombosis in MPN patients, as well as the management of dyslipidemia in MPNs, and the impact of MPN treatment on serum lipid concentrations, particularly as side/adverse effects reported in the context of clinical trials.
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Affiliation(s)
- Mihnea-Alexandru Găman
- Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, Bucharest 050474, Romania
- Department of Hematology, Center of Hematology and Bone Marrow Transplantation, Fundeni Clinical Institute, Bucharest 022328, Romania
- Department of Cellular and Molecular Pathology, Stefan S Nicolau Institute of Virology, Romanian Academy, Bucharest 030304, Romania
| | - Bahadar Singh Srichawla
- Department of Neurology, University of Massachusetts Chan Medical School, Worcester, MA 01655, United States
| | - Yong-Feng Chen
- Department of Basic Medical Sciences, School of Medicine of Taizhou University, Taizhou University, Taizhou 318000, Zhejiang Province, China
| | - Poulami Roy
- Department of Medicine, North Bengal Medical College and Hospital, West Bengal 734012, India
| | - Arkadeep Dhali
- Academic Department of Gastroenterology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield S5 7AU, United Kingdom
| | - Ahmed Nahian
- Lecom at Seton Hill, Greensburg, PA 15601, United States
| | | | - Vincent Kipkorir
- Department of Human Anatomy and Physiology, University of Nairobi, Nairobi 00100, Kenya
| | | | | | - Amelia Maria Găman
- Department of Pathophysiology, University of Medicine and Pharmacy of Craiova, Craiova 200349, Romania
- Clinic of Hematology, Filantropia City Hospital, Craiova 200143, Romania
| | - Camelia Cristina Diaconu
- Department of Internal Medicine, Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, Bucharest 050474, Romania
- Internal Medicine Clinic, Clinical Emergency Hospital of Bucharest, Bucharest 105402, Romania
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Allegra A, Mirabile G, Caserta S, Stagno F, Russo S, Pioggia G, Gangemi S. Oxidative Stress and Chronic Myeloid Leukemia: A Balance between ROS-Mediated Pro- and Anti-Apoptotic Effects of Tyrosine Kinase Inhibitors. Antioxidants (Basel) 2024; 13:461. [PMID: 38671909 PMCID: PMC11047441 DOI: 10.3390/antiox13040461] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2024] [Revised: 03/31/2024] [Accepted: 04/12/2024] [Indexed: 04/28/2024] Open
Abstract
The balanced reciprocal translocation t (9; 22) (q34; q11) and the BCR-ABL fusion gene, which produce p210 bcr-abl protein production with high tyrosine kinase activity, are characteristics of chronic myeloid leukemia, a myeloproliferative neoplasm. This aberrant protein affects several signaling pathways connected to both apoptosis and cell proliferation. It has been demonstrated that tyrosine kinase inhibitor treatment in chronic myeloid leukemia acts by inducing oxidative stress and, depending on its level, can activate signaling pathways responsible for either apoptosis or survival in leukemic cells. Additionally, oxidative stress and reactive oxygen species generation also mediate apoptosis through genomic activation. Furthermore, it was shown that oxidative stress has a role in both BCR-ABL-independent and BCR-ABL-dependent resistance pathways to tyrosine kinases, while patients with chronic myeloid leukemia were found to have a significantly reduced antioxidant level. The ideal environment for tyrosine kinase inhibitor therapy is produced by a favorable oxidative status. We discuss the latest studies that aim to manipulate the redox system to alter the apoptosis of cancerous cells.
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Affiliation(s)
- Alessandro Allegra
- Division of Hematology, Department of Human Pathology in Adulthood and Childhood ‘Gaetano Barresi’, University of Messina, 98125 Messina, Italy; (G.M.); (S.C.); (F.S.); (S.R.)
| | - Giuseppe Mirabile
- Division of Hematology, Department of Human Pathology in Adulthood and Childhood ‘Gaetano Barresi’, University of Messina, 98125 Messina, Italy; (G.M.); (S.C.); (F.S.); (S.R.)
| | - Santino Caserta
- Division of Hematology, Department of Human Pathology in Adulthood and Childhood ‘Gaetano Barresi’, University of Messina, 98125 Messina, Italy; (G.M.); (S.C.); (F.S.); (S.R.)
| | - Fabio Stagno
- Division of Hematology, Department of Human Pathology in Adulthood and Childhood ‘Gaetano Barresi’, University of Messina, 98125 Messina, Italy; (G.M.); (S.C.); (F.S.); (S.R.)
| | - Sabina Russo
- Division of Hematology, Department of Human Pathology in Adulthood and Childhood ‘Gaetano Barresi’, University of Messina, 98125 Messina, Italy; (G.M.); (S.C.); (F.S.); (S.R.)
| | - Giovanni Pioggia
- Institute for Biomedical Research and Innovation (IRIB), National Research Council of Italy (CNR), 98164 Messina, Italy;
| | - Sebastiano Gangemi
- Allergy and Clinical Immunology Unit, Department of Clinical and Experimental Medicine, University of Messina, 98100 Messina, Italy;
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Manan MR, Kipkorir V, Nawaz I, Waithaka MW, Srichawla BS, Găman AM, Diaconu CC, Găman MA. Acute myocardial infarction in myeloproliferative neoplasms. World J Cardiol 2023; 15:571-581. [PMID: 38058401 PMCID: PMC10696206 DOI: 10.4330/wjc.v15.i11.571] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Revised: 10/21/2023] [Accepted: 11/13/2023] [Indexed: 11/23/2023] Open
Abstract
Myeloproliferative neoplasms (MPNs) are a heterogeneous group of hematologic malignancies characterized by an abnormal proliferation of cells of the myeloid lineage. Affected individuals are at increased risk for cardiovascular and thrombotic events. Myocardial infarction (MI) may be one of the earliest clinical manifestations of MPNs or may be a thrombotic complication that develops during the natural course of the disease. In the present review, we examine the epidemiology, pathogenesis, clinical presentation, and management of MI in MPNs based on the available literature. Moreover, we review potential biomarkers that could mediate the MI-MPNs crosstalk, from classical biochemical tests, e.g., lactate dehydrogenase, creatine kinase and troponins, to pro-inflammatory cytokines, oxidative stress markers, and clonal hematopoiesis.
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Affiliation(s)
| | - Vincent Kipkorir
- Department of Human Anatomy and Physiology, University of Nairobi, Nairobi 00100, Kenya
| | - Iqra Nawaz
- Quaid-e-Azam Medical College, Bahawalpur 63100, Pakistan
| | | | - Bahadar Singh Srichawla
- Department of Neurology, University of Massachusetts Chan Medical School, Worcester, MA 01655, United States
| | - Amelia Maria Găman
- Department of Pathophysiology, University of Medicine and Pharmacy of Craiova, Craiova 200143, Romania
- Clinic of Hematology, Filantropia City Hospital, Craiova 200143, Romania
| | - Camelia Cristina Diaconu
- Department of Internal Medicine, Faculty of Medicine, "Carol Davila" University of Medicine and Pharmacy, Bucharest 050474, Romania
- Internal Medicine Clinic, Clinical Emergency Hospital of Bucharest, Bucharest 105402, Romania
| | - Mihnea-Alexandru Găman
- Faculty of Medicine, "Carol Davila" University of Medicine and Pharmacy, Bucharest 050474, Romania
- Department of Hematology, Center of Hematology and Bone Marrow Transplantation, Fundeni Clinical Institute, Bucharest 022328, Romania
- Department of Cellular and Molecular Pathology, Stefan S. Nicolau Institute of Virology, Romanian Academy, Bucharest 030304, Romania.
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Găman MA, Kipkorir V, Srichawla BS, Dhali A, Găman AM, Diaconu CC. Primary Arterial Hypertension and Drug-Induced Hypertension in Philadelphia-Negative Classical Myeloproliferative Neoplasms: A Systematic Review. Biomedicines 2023; 11:388. [PMID: 36830925 PMCID: PMC9952891 DOI: 10.3390/biomedicines11020388] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Revised: 01/24/2023] [Accepted: 01/25/2023] [Indexed: 01/31/2023] Open
Abstract
The impact of primary arterial hypertension (HTN) in myeloproliferative neoplasms (MPNs) remains unclear, with scant literature available, mostly focusing on cardiovascular risk factors as a singular entity or on organ-specific HTN. Furthermore, available studies reporting findings on drug-induced HTN in MPNs report varying and contradictory findings. In consideration of the above, this study set out to systematically review the available literature and shed light on the occurrence of HTN in MPNs, its association with thrombosis, as well as the drugs used in MPN management that could increase blood pressure. The literature search yielded 598 potentially relevant records of which 315 remained after the duplicates (n = 283) were removed. After we screened the titles and the abstracts of these publications, we removed irrelevant papers (n = 228) and evaluated the full texts of 87 papers. Furthermore, 13 records did not meet the inclusion criteria and were excluded from the systematic review. Finally, a total of 74 manuscripts were entered into the qualitative synthesis and included in the present systematic review. Our systematic review highlights that HTN is the most common comorbidity encountered in MPNs, with an impact on both the occurrence of thrombosis and survival. Moreover, drug-induced HTN remains a challenge in the management of MPNs. Further research should investigate the characteristics of patients with MPNs and HTN, as well as clarify the contribution of HTN to the development of thrombotic complications, survival and management in MPNs. In addition, the relationship between clonal hematopoiesis of indeterminate potential, HTN, cardiovascular disease and MPNs requires examination in upcoming assessments.
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Affiliation(s)
- Mihnea-Alexandru Găman
- Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Department of Hematology, Center of Hematology and Bone Marrow Transplantation, Fundeni Clinical Institute, 022328 Bucharest, Romania
| | - Vincent Kipkorir
- Department of Human Anatomy and Physiology, University of Nairobi, Nairobi 30197, Kenya
| | | | - Arkadeep Dhali
- Department of Internal Medicine, Nottingham University Hospitals NHS Trust, Nottingham NG7 2UH, UK
| | - Amelia Maria Găman
- Department of Pathophysiology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
- Clinic of Hematology, Filantropia City Hospital, 200143 Craiova, Romania
| | - Camelia Cristina Diaconu
- Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Department of Internal Medicine, Clinical Emergency Hospital of Bucharest, 105402 Bucharest, Romania
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Abdelghani M, Hammami H, Zidi W, Amouri H, Othmen HBH, Farrah A, Menif S. Hematological relevance of JAK2 V617F and calreticulin mutations in Tunisian patients with essential thrombocythemia. J Clin Lab Anal 2022; 36:e24522. [PMID: 35754115 PMCID: PMC9396186 DOI: 10.1002/jcla.24522] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Revised: 04/28/2022] [Accepted: 05/01/2022] [Indexed: 11/14/2022] Open
Abstract
Background The genetic investigation of essential thrombocythemia(ET) has highlighted the presence of driver mutations in ET. Janus kinase JAK2V617F and calreticulin(CALR) mutations are the most frequent driver mutations and have significantly improved the molecular diagnosis of ET. The impact of genetic heterogeneity on clinical features has not been fully elucidated. This is the first study which aimed to determine the frequency of JAK2V617F and CALR exon9 mutations in Tunisian ET patients and to establish the correlation between hematological characteristics and mutational status. Methods This study included Tunisian patients suspected with ET and was conducted between September 2017 and March 2021. Genomic DNA of patients was isolated from peripheral blood samples. JAK2V617F was detected by AS‐PCR and CALR mutations were detected by PCR/direct sequencing. Clinical and hematological characteristics were also analyzed. Results Two hundred and fifty ET patients were enrolled in this study. JAK2V617F mutation was found in 166/250 (66.4%) of patients, whereas CALR mutations were detected in 27/84 (32.1%) patients without JAK2V617F. Compared with JAK2V617F‐positive patients, those with CALR mutations showed lower hemoglobin level and lower leucocytes count (p = 0.007 and p = 0.004,respectively). CALR type 2 was the most frequent mutation of CALR detected in 55.55% of CALR mutated. Six of seven patients with thrombotic events harbored JAK2V617F mutation. Conclusion The prevalence of driver mutations JAK2V617F or CALR mutations was 77.2% in Tunisian ET patients. Moreover, patients with JAK2 V617F mutation had a higher risk of thrombosis. The mutational status is necessary to improve the diagnosis and contribute to the therapeutic decisions.
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Affiliation(s)
- Maroua Abdelghani
- LR16IPT07, Molecular and Cellular Hematology Laboratory, Pasteur Institute of Tunis, University of Tunis El Manar, Tunis, Tunisia.,Faculty of Mathematics, Physics and Natural Sciences of Tunis, University of Tunis El Manar, Tunis, Tunisia
| | - Haifa Hammami
- LR16IPT07, Molecular and Cellular Hematology Laboratory, Pasteur Institute of Tunis, University of Tunis El Manar, Tunis, Tunisia.,Faculty of Mathematics, Physics and Natural Sciences of Tunis, University of Tunis El Manar, Tunis, Tunisia
| | - Wiem Zidi
- Laboratory of Biochemistry, Rabta Hospital, Tunis, Tunisia
| | - Hassiba Amouri
- LR16IPT07, Molecular and Cellular Hematology Laboratory, Pasteur Institute of Tunis, University of Tunis El Manar, Tunis, Tunisia
| | - Hind Ben Hadj Othmen
- LR16IPT07, Molecular and Cellular Hematology Laboratory, Pasteur Institute of Tunis, University of Tunis El Manar, Tunis, Tunisia
| | - Ahlem Farrah
- LR16IPT07, Molecular and Cellular Hematology Laboratory, Pasteur Institute of Tunis, University of Tunis El Manar, Tunis, Tunisia
| | - Samia Menif
- LR16IPT07, Molecular and Cellular Hematology Laboratory, Pasteur Institute of Tunis, University of Tunis El Manar, Tunis, Tunisia
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Bhuria V, Baldauf CK, Schraven B, Fischer T. Thromboinflammation in Myeloproliferative Neoplasms (MPN)-A Puzzle Still to Be Solved. Int J Mol Sci 2022; 23:ijms23063206. [PMID: 35328626 PMCID: PMC8954909 DOI: 10.3390/ijms23063206] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Revised: 03/11/2022] [Accepted: 03/15/2022] [Indexed: 02/04/2023] Open
Abstract
Myeloproliferative neoplasms (MPNs), a group of malignant hematological disorders, occur as a consequence of somatic mutations in the hematopoietic stem cell compartment and show excessive accumulation of mature myeloid cells in the blood. A major cause of morbidity and mortality in these patients is the marked prothrombotic state leading to venous and arterial thrombosis, including myocardial infarction (MI), deep vein thrombosis (DVT), and strokes. Additionally, many MPN patients suffer from inflammation-mediated constitutional symptoms, such as fever, night sweats, fatigue, and cachexia. The chronic inflammatory syndrome in MPNs is associated with the up-regulation of various inflammatory cytokines in patients and is involved in the formation of the so-called MPN thromboinflammation. JAK2-V617F, the most prevalent mutation in MPNs, has been shown to activate a number of integrins on mature myeloid cells, including granulocytes and erythrocytes, which increase adhesion and drive venous thrombosis in murine knock-in/out models. This review aims to shed light on the current understanding of thromboinflammation, involvement of neutrophils in the prothrombotic state, plausible molecular mechanisms triggering the process of thrombosis, and potential novel therapeutic targets for developing effective strategies to reduce the MPN disease burden.
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Affiliation(s)
- Vikas Bhuria
- Institute of Molecular and Clinical Immunology, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany; (V.B.); (C.K.B.); (T.F.)
- Health-Campus Immunology, Infectiology, and Inflammation, Medical Center, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany
- Center for Health and Medical Prevention—ChaMP, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany
| | - Conny K. Baldauf
- Institute of Molecular and Clinical Immunology, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany; (V.B.); (C.K.B.); (T.F.)
- Health-Campus Immunology, Infectiology, and Inflammation, Medical Center, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany
| | - Burkhart Schraven
- Institute of Molecular and Clinical Immunology, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany; (V.B.); (C.K.B.); (T.F.)
- Health-Campus Immunology, Infectiology, and Inflammation, Medical Center, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany
- Center for Health and Medical Prevention—ChaMP, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany
- Correspondence: ; Tel.: +49-391-67-15338; Fax: +49-391-67-15852
| | - Thomas Fischer
- Institute of Molecular and Clinical Immunology, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany; (V.B.); (C.K.B.); (T.F.)
- Health-Campus Immunology, Infectiology, and Inflammation, Medical Center, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany
- Center for Health and Medical Prevention—ChaMP, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany
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Bhuria V, Baldauf CK, Schraven B, Fischer T. Thromboinflammation in Myeloproliferative Neoplasms (MPN)-A Puzzle Still to Be Solved. Int J Mol Sci 2022. [PMID: 35328626 DOI: 10.3390/ijms23063206.pmid:35328626;pmcid:pmc8954909] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/09/2023] Open
Abstract
Myeloproliferative neoplasms (MPNs), a group of malignant hematological disorders, occur as a consequence of somatic mutations in the hematopoietic stem cell compartment and show excessive accumulation of mature myeloid cells in the blood. A major cause of morbidity and mortality in these patients is the marked prothrombotic state leading to venous and arterial thrombosis, including myocardial infarction (MI), deep vein thrombosis (DVT), and strokes. Additionally, many MPN patients suffer from inflammation-mediated constitutional symptoms, such as fever, night sweats, fatigue, and cachexia. The chronic inflammatory syndrome in MPNs is associated with the up-regulation of various inflammatory cytokines in patients and is involved in the formation of the so-called MPN thromboinflammation. JAK2-V617F, the most prevalent mutation in MPNs, has been shown to activate a number of integrins on mature myeloid cells, including granulocytes and erythrocytes, which increase adhesion and drive venous thrombosis in murine knock-in/out models. This review aims to shed light on the current understanding of thromboinflammation, involvement of neutrophils in the prothrombotic state, plausible molecular mechanisms triggering the process of thrombosis, and potential novel therapeutic targets for developing effective strategies to reduce the MPN disease burden.
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Affiliation(s)
- Vikas Bhuria
- Institute of Molecular and Clinical Immunology, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany
- Health-Campus Immunology, Infectiology, and Inflammation, Medical Center, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany
- Center for Health and Medical Prevention-ChaMP, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany
| | - Conny K Baldauf
- Institute of Molecular and Clinical Immunology, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany
- Health-Campus Immunology, Infectiology, and Inflammation, Medical Center, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany
| | - Burkhart Schraven
- Institute of Molecular and Clinical Immunology, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany
- Health-Campus Immunology, Infectiology, and Inflammation, Medical Center, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany
- Center for Health and Medical Prevention-ChaMP, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany
| | - Thomas Fischer
- Institute of Molecular and Clinical Immunology, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany
- Health-Campus Immunology, Infectiology, and Inflammation, Medical Center, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany
- Center for Health and Medical Prevention-ChaMP, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany
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10
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Abedi E, Karimi M, Yaghobi R, Mohammadi H, Haghpanah S, Moghadam M, Bayat E, Rezvani A, Ramzi M. Oncogenic and tumor suppressor genes expression in myeloproliferative neoplasms: The hidden side of a complex pathology. J Clin Lab Anal 2022; 36:e24289. [PMID: 35176183 PMCID: PMC8993601 DOI: 10.1002/jcla.24289] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2021] [Revised: 11/22/2021] [Accepted: 12/21/2021] [Indexed: 11/30/2022] Open
Abstract
Background The present study aimed to explore the changes in the expressions of six tumor‐related genes in myeloproliferative neoplasms (MPNs). The study population included 130 patients with MPNs (52 with chronic myeloid leukemia (CML), 49 with essential thrombocythemia (ET), 20 with polycythemia vera (PV), and 9 with primary myelofibrosis (PMF)) and 51 healthy individuals. Methods The expression profiling of six genes (ADAMTS18, CMTM5, CDKN2B, DCC, FHIT, and WNT5B) in the peripheral blood granulocyte cells was explored by real‐time quantitative reverse transcription polymerase chain reaction. Results The patients with MPNs showed significant downregulation of CMTM5 (EFC = 0.66) and DCC (EFC = 0.65) genes in contrast to a non‐significant upregulation of ADAMTS18, CDKN2B, FHIT, and WNT5B genes. Downregulation of DCC was consistent in all subtypes of MPN (EFC range: 0.591–0.860). However, CMTM5 had a 1.22‐fold upregulation in PMF in contrast to downregulation in other MPN subtypes (EFC range: 0.599–0.775). The results revealed a significant downregulation in CMTM5 and DCC at below 60‐years of age. Furthermore, female patients showed a clear‐cut downregulation in both CMTM5 and DCC (EFC DCC: 0.436 and CMTM5: 0.570), while male patients presented a less prominent downregulation with a borderline p‐value only in DCC (EFC: 0.69; p = 0.05). Conclusions Chronic myeloid leukemia cases showed a significant upregulation of WNT5B, as a known oncogenesis gene. Two tumor suppressor genes, namely DCC and CMTM5, were downregulated in the patients with MPNs, especially in females and patients below 60 years of age.
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Affiliation(s)
- Elham Abedi
- Hematology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mehran Karimi
- Hematology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Ramin Yaghobi
- Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Hamid Mohammadi
- Department of Pediatrics, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Sezaneh Haghpanah
- Hematology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mohamad Moghadam
- Hematology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Elahe Bayat
- Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Alireza Rezvani
- Hematology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mani Ramzi
- Hematology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
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11
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Lucchesi A, Napolitano R, Bochicchio MT, Giordano G, Napolitano M. Platelets Contribution to Thrombin Generation in Philadelphia-Negative Myeloproliferative Neoplasms: The "Circulating Wound" Model. Int J Mol Sci 2021; 22:ijms222111343. [PMID: 34768772 PMCID: PMC8583863 DOI: 10.3390/ijms222111343] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2021] [Revised: 10/16/2021] [Accepted: 10/18/2021] [Indexed: 12/11/2022] Open
Abstract
Current cytoreductive and antithrombotic strategies in MPNs are mostly based on cell counts and on patient's demographic and clinical history. Despite the numerous studies conducted on platelet function and on the role of plasma factors, an accurate and reliable method to dynamically quantify the hypercoagulability states of these conditions is not yet part of clinical practice. Starting from our experience, and after having sifted through the literature, we propose an in-depth narrative report on the contribution of the clonal platelets of MPNs-rich in tissue factor (TF)-in promoting a perpetual procoagulant mechanism. The whole process results in an unbalanced generation of thrombin and is self-maintained by Protease Activated Receptors (PARs). We chose to define this model as a "circulating wound", as it indisputably links the coagulation, inflammation, and fibrotic progression of the disease, in analogy with what happens in some solid tumours. The platelet contribution to thrombin generation results in triggering a vicious circle supported by the PARs/TGF-beta axis. PAR antagonists could therefore be a good option for target therapy, both to contain the risk of vascular events and to slow the progression of the disease towards end-stage forms. Both the new and old strategies, however, will require tools capable of measuring procoagulant or prohaemorrhagic states in a more extensive and dynamic way to favour a less empirical management of MPNs and their potential clinical complications.
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MESH Headings
- Animals
- Biological Assay
- Blood Platelets/metabolism
- Humans
- Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative/drug therapy
- Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative/metabolism
- Models, Biological
- Receptors, Fibrinogen/metabolism
- Thrombin/antagonists & inhibitors
- Thrombin/biosynthesis
- Thrombophilia/physiopathology
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Affiliation(s)
- Alessandro Lucchesi
- Hematology Unit, IRCCS Istituto Scientifico Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, Italy;
| | - Roberta Napolitano
- Biosciences Laboratory, IRCCS Istituto Scientifico Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, Italy;
- Correspondence:
| | - Maria Teresa Bochicchio
- Biosciences Laboratory, IRCCS Istituto Scientifico Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, Italy;
| | - Giulio Giordano
- Internal Medicine Division, Hematology Service, Regional Hospital “A. Cardarelli”, 86100 Campobasso, Italy;
| | - Mariasanta Napolitano
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties and Infectious Disease Unit, University Hospital “P. Giaccone”, 90127 Palermo, Italy;
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12
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Sobas M, Podolak-Dawidziak M, Lewandowski K, Bator M, Wróbel T. Primary Immune Thrombocytopenia and Essential Thrombocythemia: So Different and yet Somehow Similar-Cases Series and a Review of the Literature. Int J Mol Sci 2021; 22:10918. [PMID: 34681577 PMCID: PMC8539407 DOI: 10.3390/ijms222010918] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Revised: 10/02/2021] [Accepted: 10/06/2021] [Indexed: 12/02/2022] Open
Abstract
This article collects several published cases in which immune thrombocytopenic purpura (ITP) is followed by essential thrombocythemia (ET) and vice versa. This surprising clinical condition is possible, but very rare and difficult to diagnose and manage. We have made an attempt to analyse the possible causes of the sequential appearance of ITP and ET taking into consideration the following: alteration of the thrombopoietin (TPO) receptor, the role of autoimmunity and inflammation, and cytokine modulation. A better understanding of these interactions may provide opportunities to determine predisposing factors and aid in finding new treatment modalities both for ITP and ET patients.
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Affiliation(s)
- Marta Sobas
- Department of Hematology, Blood Neoplasms and Bone Marrow Transplantation, Wroclaw Medical University, Pasteura 4, 50-367 Wroclaw, Poland; (M.P.-D.); (M.B.); (T.W.)
| | - Maria Podolak-Dawidziak
- Department of Hematology, Blood Neoplasms and Bone Marrow Transplantation, Wroclaw Medical University, Pasteura 4, 50-367 Wroclaw, Poland; (M.P.-D.); (M.B.); (T.W.)
| | - Krzysztof Lewandowski
- Hematology and Bone Marrow Transplantation Department, University of Medical Sciences, 60-569 Poznan, Poland;
| | - Michał Bator
- Department of Hematology, Blood Neoplasms and Bone Marrow Transplantation, Wroclaw Medical University, Pasteura 4, 50-367 Wroclaw, Poland; (M.P.-D.); (M.B.); (T.W.)
| | - Tomasz Wróbel
- Department of Hematology, Blood Neoplasms and Bone Marrow Transplantation, Wroclaw Medical University, Pasteura 4, 50-367 Wroclaw, Poland; (M.P.-D.); (M.B.); (T.W.)
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13
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Găman MA, Cozma MA, Dobrică EC, Crețoiu SM, Găman AM, Diaconu CC. Liquid Biopsy and Potential Liquid Biopsy-Based Biomarkers in Philadelphia-Negative Classical Myeloproliferative Neoplasms: A Systematic Review. Life (Basel) 2021; 11:677. [PMID: 34357048 PMCID: PMC8304270 DOI: 10.3390/life11070677] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Revised: 07/07/2021] [Accepted: 07/09/2021] [Indexed: 12/14/2022] Open
Abstract
Myeloproliferative neoplasms (MPNs) are rare, clonal disorders of the hematopoietic stem cell in which an uncontrolled proliferation of terminally differentiated myeloid cells is noted. Polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) are included in the category of Philadelphia-negative, so-called classical MPNs. The potential applications of liquid biopsy and liquid biopsy-based biomarkers have not been explored in MPNs until now. Thus, a systematic search was computed in PubMed/MEDLINE, Web of Science and The Cochrane Library and, in total, 198 potentially relevant papers were detected. Following the removal of duplicates (n = 85), 113 records were screened. After the exclusion of irrelevant manuscripts based on the screening of their titles and abstracts (n = 81), we examined the full texts of 33 manuscripts. Finally, after we applied the exclusion and inclusion criteria, 27 original articles were included in this review. Overall, the data analyzed in this review point out that liquid biopsy and liquid biopsy-based biomarkers (cell-free DNA, extracellular vesicles, microparticles, circulating endothelial cells) could be used in MPNs for diagnostic and prognostic purposes. Future research is needed to clarify whether this technique can be employed to differentiate between MPN subtypes and secondary causes of erythrocytosis, thrombocytosis and myelofibrosis, as well as to predict the development of thrombosis.
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Affiliation(s)
- Mihnea-Alexandru Găman
- Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania;
- Department of Hematology, Center of Hematology and Bone Marrow Transplantation, Fundeni Clinical Institute, 022328 Bucharest, Romania
| | - Matei-Alexandru Cozma
- Department of Gastroenterology, Colentina Clinical Hospital, 020125 Bucharest, Romania;
| | - Elena-Codruța Dobrică
- Department of Pathophysiology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania; (E.-C.D.); (A.M.G.)
- Department of Dermatology, “Elias” University Emergency Hospital, 011461 Bucharest, Romania
| | - Sanda Maria Crețoiu
- Department of Cell and Molecular Biology and Histology, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Amelia Maria Găman
- Department of Pathophysiology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania; (E.-C.D.); (A.M.G.)
- Clinic of Hematology, Filantropia City Hospital, 200143 Craiova, Romania
| | - Camelia Cristina Diaconu
- Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania;
- Department of Internal Medicine, Clinical Emergency Hospital of Bucharest, 105402 Bucharest, Romania
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14
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Pan Q, Hui D, Hu C. A Variant of IL1B Is Associated with the Risk and Blood Lipid Levels of Myocardial Infarction in Eastern Chinese Individuals. Immunol Invest 2021; 51:1162-1169. [PMID: 33941028 DOI: 10.1080/08820139.2021.1914081] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
In this study, we determined to interpret the effects of the interleukin (IL)1B gene rs1143634 C/T polymorphism on myocardial infarction (MI) risk. This study, conducted in a Chinese Han population, recruited 369 MI patients and 465 controls. The variant of IL1B gene (rs1143634 C/T polymorphism) was genotyped by PCR-RFLP method. In this study, a significant link was shown between the IL1B rs1143634 C/T polymorphism and MI risk. We found that the IL1B rs1143634 C/T polymorphism enhanced the risk of MI in this population. Subgroup analysis detected that the IL1B rs1143634 C/T polymorphism associated with MI susceptibility in males, smokers, and individuals with diabetes mellitus. In addition, the IL1B rs1143634 C/T polymorphism was related with the levels of blood lipids including low-density lipoprotein (LDL), and total cholesterol (TC). This study uncovers that the IL1B rs1143634 C/T polymorphism may associate with the risk and blood lipid levels of MI in an Eastern Chinese Han population.Abbreviations: MI: myocardial infarction; IL-1: Interleukin-1; SNP: single nucleotide polymorphism; BMI: Body Mass Index; HDL: high-density lipoprotein; TC: total cholesterol; TG: triglyceride; LDL: low-density lipoprotein; PCR: polymerase chain reaction; 95% CI: 95% confidence interval; OR: odds ratio.
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Affiliation(s)
- Quanhua Pan
- Department of Cardiology Surgery, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huaian, China
| | - Ding Hui
- Department of Cardiology Surgery, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huaian, China
| | - Chuangxian Hu
- Department of Cardiology Surgery, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huaian, China
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15
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Gao S, Hu J, Li Y. Targeting of the Alox12-12-HETE in Blast Crisis Chronic Myeloid Leukemia Inhibits Leukemia Stem/Progenitor Cell Function. Cancer Manag Res 2020; 12:12509-12517. [PMID: 33312001 PMCID: PMC7726836 DOI: 10.2147/cmar.s280554] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2020] [Accepted: 11/11/2020] [Indexed: 12/14/2022] Open
Abstract
Introduction Chronic myeloid leukemia (CML) is a myeloid malignancy characterized by the oncogene BCR-ABL. CML responds well to therapy targeting BCR-ABL in the chronic phase but is resistant to treatment when it progresses to the blast phase (BP). This study attempted to address whether arachidonate 12-lipoxygenase (Alox12) confers to CML drug resistance. Materials and Methods We analyzed the expression of Alox12 using Western blotting, ELISA, and RT-PCR methods. Loss of functional analysis was performed using cellular activity assays on CML and normal hematopoietic stem/progenitor cells (HSPCs). Results Alox12 and 12-Hydroxyeicosatetraenoic acid (12-HETE) are overexpressed in BP-CML but not HSPCs, and that Alox12-12-HETE axis is regulated by BCR-ABL. The Alox12-12-HETE axis is required for CML. Specific Alox12 inhibitor inhibits colony formation, survival, and self-renewal capacity in BP-CML HSPCs, and to a significantly greater extent than in normal HSPCs. Of note, the Alox12 inhibitor significantly augments dasatinib’s efficacy in BP-CML HSPCs. Mechanism studies show that Alox12 inhibition does not affect activities of essential signaling pathways involved in maintaining stem cell function, such as Wnt, p53, and bone morphogenetic protein (BMP). In contrast, we show that Alox12 inhibition disrupts nicotinamide adenine dinucleotide phosphate (NADPH) homeostasis and induces oxidative stress and damage in CML HSPCs and committed cells. Conclusion Alox12-12-HETE axis is a specific and critical regulator of BP-CML HSPCs functions. Pharmacological inhibition of Alox12 may be useful in BP-CML.
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Affiliation(s)
- Si Gao
- Department of Haematology and Rheumatology, Wuhan Fourth Hospital, Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.,The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430014, People's Republic of China
| | - Jialin Hu
- Department of General Medicine, Wuhan Fourth Hospital, Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China
| | - Yong Li
- Department of Pharmacy, Wuhan Fourth Hospital; Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China
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16
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Impact of dehydroepiandrosterone (DHEA) supplementation on testosterone concentrations and BMI in elderly women: A meta-analysis of randomized controlled trials. Complement Ther Med 2020; 56:102620. [PMID: 33220453 DOI: 10.1016/j.ctim.2020.102620] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2020] [Revised: 11/10/2020] [Accepted: 11/11/2020] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Despite the fact that numerous clinical studies have evaluated the positive effects of dehydroepiandrosterone (DHEA) supplementation on testosterone concentrations and on the body mass index (BMI), more evidence is needed to certify that DHEA is a BMI-reducing agent in the elderly. This meta-analysis aims to clarify the various incompatible results and investigate the impact of DHEA supplementation on serum testosterone levels and lean body mass in elderly women. METHODS Four scientific databases (EMBASE, PubMed/MEDLINE, Scopus and Web of Science) were searched from inception until 20 August 2020 for trials comparing DHEA with placebo. Results were presented as weighted mean differences (WMDs) and 95 % confidence intervals (CIs) based on the random effects model (DerSimonian-Laird approach). RESULTS Nine arms with 793 subjects reported testosterone as an outcome measure. The overall results demonstrated that testosterone levels increased significantly after DHEA administration in elderly women (WMD: 17.52 ng/dL, 95 % CI: 6.61, 28.43, P = 0.002). In addition, DHEA administration significantly decreased the BMI (WMD:-0.39 kg/m2, I2 = 0.0 %). CONCLUSION The results of the current meta-analysis support the use of DHEA supplementation for increasing testosterone concentrations in elderly women.
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17
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Deng ZF, Zhang ZJ, Sheng PY, Fu M, Xu DL, He AS, Liao WM, Kang Y. Effect of 3 different anticoagulants on hidden blood loss during total hip arthroplasty after tranexamic acid. Medicine (Baltimore) 2020; 99:e22028. [PMID: 32899057 PMCID: PMC7478743 DOI: 10.1097/md.0000000000022028] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Comparison of different anticoagulants in blood management and complications with tranexamic acid (TXA) in total hip arthroplasty (THA) is unclear. Our aim was to compare the efficacy and safety among receiving nadroparin calcium, enoxaparin sodium or rivaroxaban after TXA in THA.150 patients undergoing primary unilateral THA were received 15 mg/kg intravenous TXA (IV-TXA) before skin incision, followed by 1 of nadroparin calcium (Group A), enoxaparin sodium (Group B), or rivaroxaban (Group C) randomly during hospitalization. The primary outcome was hidden blood loss (HBL). Other outcomes such as the maximum hemoglobin (Hb) drop, total blood loss (TBL), the volume of drainage, transfusion rate, length of hospital stay (LOS), and complications were also compared.There were no statistically significant differences in HBL, the maximum hemoglobin (Hb) drop, transfusion rate, and complications among 3 groups. LOS was significantly higher for patients in Group B than Group A (P = .026). Neither deep venous thrombosis (DVT) nor pulmonary embolism (PE) occurred in any group.There were no differences in efficacy and safety in patients undergoing THA receiving nadroparin calcium, enoxaparin sodium, or rivaroxaban after anti-fibrinolysis with TXA.
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18
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Cheng S, Guo S, He H, Kaminga AC, Xu H. Clinical value of long noncoding RNA ZEB1 anti-sense1 in cancer patients: A meta-analysis. Medicine (Baltimore) 2020; 99:e21307. [PMID: 32756112 PMCID: PMC7402794 DOI: 10.1097/md.0000000000021307] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND The high expression of long noncoding RNA ZEB1 anti-sense1 (ZEB1-AS1) has been reported in several types of cancer. However, most studies investigating this phenomenon were either case reports or used small patient samples. The objective of this meta-analysis was to clarify the potential clinical values of ZEB1-AS1 in various cancers. MATERIALS AND METHODS The PubMed-MEDLINE, Web of Science, and EMBASE databases were searched, using systematic search terms, to find relevant research reports on this subject. The combined hazards ratios (HRs) and corresponding 95% confidence intervals (CIs) were calculated to explore the association between ZEB1-AS1 expression and overall survival (OS). The combined odd ratios (ORs) were calculated to evaluate the association between ZEB1-AS1 expression and pathological parameters. Data analysis was conducted in R software version 3.4.2. and Stata version 12.0 (College Station, TX: Stata Corp LP). RESULTS Ten studies including 963 cancer patients were selected as suitable for this study. The pooled hazards ratio (HR) indicated that high ZEB1-AS1 expression was strongly associated with poor OS (pooled HR = 2.26, 95% CI: 1.80-2.85, P < .0001) in the Chinese cancer patients. Also, a high expression of ZEB1-AS1 was related to metastasis (pooled HR = 3.38, 95% CI: 1.91-6.00, P < .0001), and advanced tumor stage (pooled HR = 0.48, 95% CI: 0.29-0.81, P = .005). The up-regulation of ZEB1-AS1 was not significantly associated with histological differentiation (P = .39), sex (P = .001), and age (P = .372) of cancer patients. CONCLUSION The high expression of ZEB1-AS1 significantly predicted poor OS, poor metastasis, and high tumor stage in cancer patients, demonstrating that high ZEB1-AS1 expression may serve as a biomarker of poor prognosis in the Chinese cancer patients.
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Affiliation(s)
- Sixiang Cheng
- Department of Social Medicine and Health Management
- College of Data Science and Information Engineering, Guizhou Minzu University, Guiyang, Guizhou Province
| | - Shengyu Guo
- Department of Social Medicine and Health Management
| | - Hairong He
- School of Computer and Communication Engineering, Changsha University of Science and Technology
| | - Atipatsa Chiwanda Kaminga
- Department of Mathematics and Statistics, Mzuzu University, Luwinga, Mzuzu, Malawi
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, Hunan, China
| | - Huilan Xu
- Department of Social Medicine and Health Management
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19
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Stefaniuk P, Szymczyk A, Podhorecka M. The Neutrophil to Lymphocyte and Lymphocyte to Monocyte Ratios as New Prognostic Factors in Hematological Malignancies - A Narrative Review. Cancer Manag Res 2020; 12:2961-2977. [PMID: 32425606 PMCID: PMC7196794 DOI: 10.2147/cmar.s245928] [Citation(s) in RCA: 57] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2020] [Accepted: 03/11/2020] [Indexed: 12/11/2022] Open
Abstract
Despite the presence of many hematological prognostic indexes, clinical course and overall survival are often highly variable even within the same patient subgroup. Recent studies suggest that simple, cost-effective, low-risk tests such as neutrophil to lymphocyte ratio (NLR) and lymphocyte to monocyte ratio (LMR) may be used to evaluate the prognosis. Their role has been well confirmed in diffuse large B-cell lymphoma (DLBCL), Hodgkin lymphoma (HL) and multiple myeloma (MM), but until now the prognostic significance of NLR and LMR in leukemias has not been widely reported. In this article, we analyze the literature data on prognostic value of NLR and LMR in haematological malignancies in the context of classic prognostic factors and clinical course.
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Affiliation(s)
- Paulina Stefaniuk
- Department of Haematooncology and Bone Marrow Transplantation, Medical University of Lublin, Lublin, Poland
| | - Agnieszka Szymczyk
- Department of Clinical Transplantology, Medical University of Lublin, Lublin, Poland
| | - Monika Podhorecka
- Department of Haematooncology and Bone Marrow Transplantation, Medical University of Lublin, Lublin, Poland
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20
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Lu N, Neoh CL, Ruan Z, Zhao L, Ying L, Zhang X, Chen S, Xu L. Essential Thrombocythaemia with Concomitant Waldenström Macroglobulinaemia: Case Report and Literature Review. Onco Targets Ther 2020; 13:3431-3435. [PMID: 32425546 PMCID: PMC7186880 DOI: 10.2147/ott.s245950] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Accepted: 04/09/2020] [Indexed: 11/28/2022] Open
Abstract
Essential thrombocythaemia (ET) and Waldenström macroglobulinaemia (WM) are two distinct disorders. Studies have reported several cases of myeloproliferative neoplasms (MPNs) with concomitant plasma cell dyscrasia. However, there were no reported cases of ET with concomitant WM to date. Here, we present a 55-year-old Chinese man with thrombocytosis and raised immunoglobulin level. Further investigations led to a diagnosis of ET and coexistent WM. Next-generation sequencing (NGS) of his bone marrow identified 3 mutated genes: JAK2 V617F, MYD88 L265P, and ATM F1036L. After being treated with pegylated interferon and low-dose aspirin, his platelet count normalized and immunoglobulin M (IgM) level reduced. To the best of our knowledge, this is the first reported case of dual pathology ET with WM.
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Affiliation(s)
- Nina Lu
- Department of Hematology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang 318000, People's Republic of China
| | - Chin Loon Neoh
- Department of Hematology, Royal Marsden Hospital, London SW3 6JJ, UK
| | - Zhengying Ruan
- Department of Pathology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang 318000, People's Republic of China
| | - Lei Zhao
- Department of Laboratory Medicine, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang 318000, People's Republic of China
| | - Limei Ying
- Department of Hematology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang 318000, People's Republic of China
| | - Xiaochang Zhang
- Department of Hematology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang 318000, People's Republic of China
| | - Sai Chen
- Department of Hematology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang 318000, People's Republic of China
| | - Linglong Xu
- Department of Hematology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang 318000, People's Republic of China
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