• BCR::ABL1
• Blast phase CML (BP-CML)
• Chronic myeloid leukemia (CML)
• Chronic phase CML (CP-CML)
• FLT3
• KF1601
• TKI resistance
• Tyrosine kinase inhibitor (TKI)

• Humans
• Animals
• fms-Like Tyrosine Kinase 3/antagonists & inhibitors
• fms-Like Tyrosine Kinase 3/genetics
• fms-Like Tyrosine Kinase 3/metabolism
• Drug Resistance, Neoplasm/drug effects
• Mice
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive/metabolism
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics
• Fusion Proteins, bcr-abl/antagonists & inhibitors
• Fusion Proteins, bcr-abl/genetics
• Xenograft Model Antitumor Assays
• Protein Kinase Inhibitors/pharmacology
• Blast Crisis/drug therapy
• Blast Crisis/pathology
• Blast Crisis/metabolism
• Blast Crisis/genetics
• Signal Transduction/drug effects
• K562 Cells
• Pyridazines/pharmacology
• Cell Proliferation/drug effects
• Disease Models, Animal
• Mutation
• Imidazoles

• 2020M3F7A1094077 National Research Foundation of Korea
• 2017M3A9G4052951 National Research Foundation of Korea

• Chronic myeloid leukemia
• Diagnosis
• Disease progression
• Hsa_circ_0002903
• Hsa_circ_0006010
• Prognostic biomarkers
• Surveillance

• Humans
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive/blood
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis
• Biomarkers, Tumor/blood
• Biomarkers, Tumor/genetics
• Disease Progression
• Male
• Female
• RNA, Circular/blood
• RNA, Circular/genetics
• Prognosis
• Middle Aged
• Adult
• Aged
• Case-Control Studies

• Y20220123 and Y20220744 the Basic Scientific Research Project of Wenzhou City
• Y20220123 and Y20220744 the Basic Scientific Research Project of Wenzhou City
• 2021KY216 the Medical and Health Research Science and Technology Plan Project of Zhejiang Province
• LGF20H200005 the Basic Public Welfare Technology Research Project of Zhejiang Province

• cancer models
• chronic myeloid leukaemia
• preclinical research

• Pyridazines/therapeutic use
• Pyridazines/administration & dosage
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology
• Imidazoles/therapeutic use
• Imidazoles/administration & dosage
• Mutation
• Humans
• Blast Crisis/genetics
• Blast Crisis/drug therapy
• Blast Crisis/pathology
• Animals
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Mice
• Fusion Proteins, bcr-abl/genetics
• Protein Kinase Inhibitors/therapeutic use
• Protein Kinase Inhibitors/pharmacology
• Niacinamide/analogs & derivatives
• Pyrazoles

• 00023736 Ministerstvo Zdravotnictví Ceské Republiky (Ministry of Health of the Czech Republic)
• 492222 Grantová Agentura, Univerzita Karlova (Charles University Grant Agency)
• European Treatment and Outcome for CML 2022

• BCR::ABL1
• Chronic myeloid leukaemia
• Quality-of-life
• Treatment-free remission
• Tyrosine kinase inhibitor

• Humans
• Protein Kinase Inhibitors/therapeutic use
• Fusion Proteins, bcr-abl/genetics
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive/etiology
• Remission Induction
• Biology

• Humans
• Male
• Cross-Sectional Studies
• Female
• Ethiopia/epidemiology
• Adult
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive/blood
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology
• Hospitals, Teaching
• Middle Aged
• Young Adult
• Adolescent
• Tertiary Care Centers/statistics & numerical data
• Aged
• Cytogenetic Analysis
• Fusion Proteins, bcr-abl/genetics
• Tertiary Healthcare

• BCR–ABL1 gene fusion
• chronic myeloid leukemia
• hematopoietic stem cell transplant
• survival
• treatment-free remission
• tyrosine kinase inhibitors

• BCR-ABL
• Biomarkers
• CML
• Oncogenes

• Humans
• Imatinib Mesylate/therapeutic use
• Imatinib Mesylate/pharmacology
• Genes, abl
• Pyrimidines/therapeutic use
• Piperazines/therapeutic use
• Benzamides/pharmacology
• Benzamides/therapeutic use
• Drug Resistance, Neoplasm/genetics
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive/metabolism
• Fusion Proteins, bcr-abl/genetics
• Fusion Proteins, bcr-abl/metabolism
• Fusion Proteins, bcr-abl/pharmacology
• Protein Kinase Inhibitors/therapeutic use
• Protein Kinase Inhibitors/pharmacology

• Adverse events
• Cancer
• Immunotherapy
• Nursing practice
• Oncology
• Targeted therapy

• Humans
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics
• Blast Crisis/therapy
• Blast Crisis/diagnosis
• Treatment Outcome
• Disease Progression
• Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics

• chronic myeloid leukemia
• genomic factors
• prognosis
• risk assessment

• Humans
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics
• Chromosome Aberrations
• Blast Crisis
• Risk Assessment

• Chronic myeloid leukemia
• Chronic phase
• Hyperleukocytosis
• Intracerebral hemorrhage
• Intracranial involvement
• Leukostasis

• Humans
• Blast Crisis/drug therapy
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics
• Hematopoietic Stem Cell Transplantation
• Protein Kinase Inhibitors/therapeutic use

• Chronic myeloid leukemia
• additional chromosomal abnormality
• blast crisis
• stem cell transplant
• tyrosine kinase inhibitor

Daphnoretin extracted from the stem and roots of Wikstroemia indica (L.) C.A. Mey has been shown to possess antiviral and antitumor activities. Herein, we hypothesized that daphnoretin might induce megakaryocytic differentiation, thereby inhibiting the proliferation of cells and serving as a differentiation therapy agent for chronic myeloid leukemia (CML). Daphnoretin-treated K562 and HEL cells were examined for growth inhibition, cell morphology, and megakaryocyte-specific markers. Potential mechanisms of megakaryocytic differentiation of daphnoretin-treated K562 cells were evaluated. The results showed that daphnoretin inhibited the growth of K562 and HEL cells in a dose- and time-dependent manner. Flow cytometry analyses revealed that daphnoretin treatment slightly increased the proportion of sub-G1 and polyploid cells compared to that of dimethyl sulfoxide (DMSO)-treated control cells. Morphological examination showed that daphnoretin-treated K562 and HEL cells exhibited enlarged contours and multinucleation as megakaryocytic characteristics compared to DMSO-treated control cells. Daphnoretin treatment also dramatically enhanced the expression of megakaryocytic markers CD61 and CD41. Under optimal megakaryocytic differentiation conditions, daphnoretin increased the phosphorylation of STAT3 but not STAT5. In summary, daphnoretin inhibited cell growth and induced megakaryocytic differentiation in K562 and HEL cells. The efficacy of daphnoretin in vivo and in patients with CML may need further investigations for validation.

• daphnoretin
• differentiation
• megakaryocyte
• myeloid leukemia
• protein kinase C

• Autophagy
• apoptosis
• leukemia stem cells
• oxidative phosphorylation
• treatment-free remission

• Apoptosis
• Drug Resistance, Neoplasm
• Fusion Proteins, bcr-abl/genetics
• Humans
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy
• Neoplastic Stem Cells
• Protein Kinase Inhibitors/adverse effects

• Abl tyrosine kinase
• Apoptosis
• Chronic myelogenous leukemia
• Gypsogenin derivatives
• Imatinib
• Molecular docking

• Humans
• Imatinib Mesylate/pharmacology
• Fusion Proteins, bcr-abl/genetics
• Fusion Proteins, bcr-abl/metabolism
• Molecular Docking Simulation
• Benzamides/pharmacology
• Pyrimidines/pharmacology
• Piperazines
• Drug Resistance, Neoplasm
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive/metabolism
• Apoptosis
• Protein Kinase Inhibitors/pharmacology
• Protein Kinase Inhibitors/chemistry

• accelerated phase/blast crisis
• chronic myeloid leukemia
• cost of care
• fourth-line therapy
• healthcare resource utilization
• third-line therapy

• Medicare
• chronic myeloid leukemia
• costs
• economic burden
• healthcare resource utilization
• treatment patterns
• tyrosine kinase inhibitors

• cancer
• molecular medicine

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affecting multiple organ systems. It can cause severe cytokine storms leading to intensive care unit admission requiring mechanical ventilation. However, there have been few studies establishing the outcomes of chronic myeloid leukemia (CML) patients on tyrosine kinase inhibitors who are infected with COVID-19. We present a 69-year-old male with a history of CML on imatinib therapy with COVID-19 who developed acute respiratory distress syndrome needing mechanical ventilatory support, shock requiring vasopressors, and worse outcome secondary to blast crisis.

Chronic myeloid leukaemia (CML) is a type of blood cancer that is currently well-managed with drugs that target cancer-causing proteins. However, a significant proportion of CML patients do not respond to those drug treatments or relapse when they stop those drugs because the cancer cells in those patients stop relying on that protein and instead develop a new way to survive. Therefore, new treatment strategies may be necessary for those patients. In this review, we discuss those additional survival pathways and outline combination treatment strategies to increase responses and clinical outcomes, improving the lives of CML patients.

Tyrosine kinase inhibitors (TKIs) have revolutionised the management of chronic myeloid leukaemia (CML), with the disease now having a five-year survival rate over 80%. The primary focus in the treatment of CML has been on improving the specificity and potency of TKIs to inhibit the activation of the BCR::ABL1 kinase and/or overcoming resistance driven by mutations in the BCR::ABL1 oncogene. However, this approach may be limited in a significant proportion of patients who develop TKI resistance despite the effective inhibition of BCR::ABL1. These patients may require novel therapeutic strategies that target both BCR::ABL1-dependent and BCR::ABL1-independent mechanisms of resistance. The combination treatment strategies that target alternative survival signalling, which may contribute towards BCR::ABL1-independent resistance, could be a successful strategy for eradicating residual leukaemic cells and consequently increasing the response rate in CML patients.

• BCR::ABL1-independent mechanism of TKI resistance
• chronic myeloid leukaemia
• combination treatments
• therapy resistance
• tyrosine kinase inhibitors

• bronchoalveolar epithelial cells
• chronic myelogenous leukemia
• sars-cov-2
• tyrosine kinase inhibitor

• Humans
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy
• Protein Kinase Inhibitors/therapeutic use
• Public Health
• SARS-CoV-2
• COVID-19 Drug Treatment

• Blast crisis
• CML
• TKI
• chronic myeloid leukemia
• hypomethylating agents
• myeloid blastic phase
• novel agents
• tyrosine kinase inhibitor
• venetoclax

• Adolescent
• Adult
• Antineoplastic Combined Chemotherapy Protocols/adverse effects
• Cytarabine/adverse effects
• Female
• Granulocyte Colony-Stimulating Factor/adverse effects
• Humans
• Idarubicin/adverse effects
• Imidazoles/adverse effects
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy
• Male
• Pyridazines/adverse effects
• Vidarabine/adverse effects
• Vidarabine/analogs & derivatives

• 12045 Blood Cancer UK
• 25354 Cancer Research UK

Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of patients with chronic myeloid leukemia (CML). However, continued use of these inhibitors has contributed to the increase in clinical resistance and the persistence of resistant leukemic stem cells (LSCs). So, there is an urgent need to introduce additional targeted and selective therapies to eradicate quiescent LSCs, and to avoid the relapse and disease progression. Here, we focused on emerging BCR-ABL targeted and non-BCR-ABL targeted drugs employed in clinical trials and on alternative CML treatments, including antioxidants, oncolytic virus, engineered exosomes, and natural products obtained from marine organisms that could pave the way for new therapeutic approaches for CML patients.

• Non-BCR-ABL targeted drugs
• antioxidants
• chronic myeloid leukemia
• exosomes
• marine organisms
• oncolytic therapy
• quiescent leukemia stem cells
• tyrosine kinase inhibitors

• BCR-ABL
• CML LSCs
• Chronic myeloid leukemia (CML)
• Leukemia stem cells (LSCs)
• Tyrosine kinase inhibitors (TKIs)

• Apoptosis
• Chronic Disease
• Humans
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics
• Neoplastic Stem Cells/metabolism
• Protein Kinase Inhibitors/pharmacology
• Protein Kinase Inhibitors/therapeutic use
• Tumor Microenvironment

• Blast Crisis/diagnosis
• Blast Crisis/therapy
• Disease Management
• Disease Progression
• Female
• Hematopoietic Stem Cell Transplantation
• Humans
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive/therapy
• Middle Aged
• Protein Kinase Inhibitors/therapeutic use

Patients with hematological malignancies are at an increased risk of SARS‐CoV‐2 disease (COVID‐19) and adverse outcome. However, a low mortality rate has been reported in patients with chronic myeloid leukemia (CML). Preclinical evidence suggests that tyrosine kinase inhibitors (TKIs) may have a protective role against severe COVID‐19.

We conducted a cross‐sectional study of 564 consecutive patients with CML who were tested for anti‐SARS‐CoV‐2 IgG/IgM antibodies at their first outpatient visit between May and early November 2020 in five hematologic centers representative of three Italian regions.

The estimated serological prevalence of SARS‐CoV‐2 infection in patients with CML after the first pandemic wave was similar to that in the general population (about 2%), both at national and regional levels. CML patients with positive anti‐SARS‐CoV‐2 serology were more frequently male (p = 0.027) and active workers (p = 0.012), while there was no significant association with TKI treatment type. Only 3 out of 11 IgG‐positive patients had previously received a molecular diagnosis of COVID‐19, while the remainders were asymptomatic or with mild symptoms.

Our data confirm that the course of SARS‐CoV‐2 infection in patients with CML is generally mild and reassure about the safety of continuing TKIs during the COVID‐19 pandemic. Furthermore, we suggest that patients with CML succeed to mount an antibody response after exposure to SARS‐CoV‐2, similar to the general population.

• COVID-19
• TKIs
• chronic myeloid leukemia
• prevalence
• serological tests

Since the introduction of tyrosine kinase inhibitors as primary therapy for patients with chronic myeloid leukemia (CML), the prognosis of these patients has improved significantly, and the number of patients who progress to the blast phase has decreased considerably. We report the case of a 35 year-old CML patient in accelerated phase treated with nilotinib, who presents a severe COVID-19 infection requiring non-invasive ventilation, and who subsequently presents a multiple cranial nerve palsy revealing a blast crisis of his CML. Multiple cranial nerve palsy is a sign of neurological involvement of CML in its blast phase. The blast crisis represents a real challenge for the clinician, especially during COVID-19 infection. The treatment remains the association of a tyrosine kinase inhibitors with a chemotherapy protocol, as well as the administration of methotrexate and cytarabine by intrathecal and intravenous infusion in high doses. Despite the importance of the association of CML with COVID-19 infection, there is not yet enough data to know the true impact of this infection on the evolution of this hemopathy.

• Blast Crisis
• Chronic Myeloid Leukemia
• Covid-19
• Cranial Nerve Palsy
• Tyrosine Kinase Inhibitor

• ATRA
• BCR-ABL
• Chronic Myeloid Leukemia
• Imatinib Mesylate
• MDR

• Anthracyclines
• Cancer therapy
• Leukaemia
• Multidrug resistance
• Reductase

• blast crisis
• chronic myeloid leukemia
• management
• mechanism
• monitor

The natural course of untreated chronic myeloid leukemia (CML) is progression to an aggressive blast phase. Even in the current era of BCR-ABL1 tyrosine kinase inhibitors (TKIs), the outcomes of blast phase CML remain poor with no consensus frontline treatment approach.

We retrospectively analyzed the response rates and survival outcomes of 104 consecutive patients with myeloid blast phase CML (CML-MBP) treated from 2000 to 2019 based on 4 different frontline treatment approaches: intensive chemotherapy (IC) + TKI (n = 20), hypomethylating agent (HMA) + TKI (n = 20), TKI alone (n = 56), or IC alone (n = 8). We also evaluated the impact of TKI selection and subsequent allogeneic stem cell transplant (ASCT) on patient outcomes.

Response rates were similar between patients treated with IC + TKI and HMA + TKI. Compared to treatment with TKI alone, treatment with IC/HMA + TKI resulted in a higher rate of complete remission (CR) or CR with incomplete count recovery (CRi) (57.5% vs 33.9%, p < 0.05), a higher complete cytogenetic response rate (45% vs 10.7%, p < 0.001), and more patients proceeding to ASCT (32.5% vs 10.7%, p < 0.01). With a median follow-up of 6.7 years, long-term outcomes were similar between the IC + TKI and HMA + TKI groups. Combination therapy with IC/HMA + TKI was superior to therapy with TKI alone, including when analysis was limited to those treated with a 2nd/3rd-generation TKI. When using a 2nd/3rd-generation TKI, IC/HMA + TKI led to lower 5-year cumulative incidence of relapse (CIR; 44% vs 86%, p < 0.05) and superior 5-year event-free survival (EFS; 28% vs 0%, p < 0.05) and overall survival (OS; 34% vs 8%, p = 0.23) compared to TKI alone. Among patients who received IC/HMA + TKI, EFS and OS was superior for patients who received a 2nd/3rd generation TKI compared to those who received imatinib-based therapy. In a landmark analysis, 5-year OS was higher for patients who proceeded to ASCT (58% vs 22%, p = 0.12).

Compared to patients treated with TKI alone for CML-MBP, treatment with IC + TKI or HMA + TKI led to improved response rates, CIR, EFS, and OS, particularly for patients who received a 2nd/3rd-generation TKI. Combination therapy with IC + TKI or HMA + TKI, rather than a TKI alone, should be considered the optimal treatment strategy for patients with CML-MBP.

The online version contains supplementary material available at 10.1186/s13045-021-01106-1.

• Blast phase
• CML
• Chemotherapy
• Hypomethylating agent
• TKI

Emerging resistance to the tyrosine kinase inhibitors that target the BCR-ABL1 oncoprotein has prompted research for novel therapeutics against chronic myeloid leukemia (CML). Herein, we evaluated the tumor inhibitory properties of the human Wharton’s jelly stem cells (hWJSCs) co-culture (hWJSC-CC) and their extracts, namely, the hWJSC-conditioned medium (hWJSC-CM; 100%) and hWJSC-lysate (hWJSC-L; 15 μg/ml), on a CML cell line K562 in vitro. The hWJSCs expressed mesenchymal stem cell (MSC)-related cluster of differentiation (CD) markers and demonstrated mesodermal tissue differentiation potential. The cell metabolic activity showed a mean maximal decrease in the K562 cells by 49.12, 41.98, and 68.80% following treatment with the hWJSC-CC, hWJSC-CM, and hWJSC-L, respectively, at 72 h. The sub-G1 population in the cell cycle was decreased by 3.2, 4.5, and 3.8% following treatment with the hWJSC-CC, hWJSC-CM, and hWJSC-L, whereas the G2/M cell population was increased by 13.7 and 12.5% with the hWJSC-CM and hWJSC-L, respectively, at 48 h. Annexin V–allophycocyanin (APC) assay showed an increase in the apoptotic cells by 4.0, 3.9, and 4.5% at 48 h. The expression of pro-apoptotic BAX and CASP3 genes were increased, whereas BIRC5 (Survivin) was decreased compared with the control. The pro-inflammation-related genes, namely, IFN-γ, TNF-α, IL-1β, IL-6, IL-8, and IL-12A, were decreased, whereas the anti-inflammatory genes, namely, IL-4 and IL-10, were increased following treatment with the hWJSC-CC, hWJSC-CM, and hWJSC-L at 48 h. Multiplex bead-based cytokine assay also demonstrated decreases in the pro-inflammatory cytokines (IFN-γ, TNF-α, IL-1β, IL-6, and IL-12) and an increase in the anti-inflammatory cytokine (IL-10) compared with the control. The pro-inflammatory cytokine IL-8 showed an increase with the hWJSC-CC and decreases with both the hWJSC-CM and the hWJSC-L. The hWJSCs and their extracts inhibited the K562 cells by causing cell cycle arrest and inducing apoptosis via the soluble cellular factors. However, an in vivo evaluation is necessary to unravel the true potential of the hWJSCs and their extracts before its use in CML inhibition.

• apoptosis
• cell cycle
• chronic myeloid leukemia
• cytokines
• gene expression
• human Wharton’s jelly stem cells

• Breakpoint cluster region-Abelson murine leukemia
• Chronic myeloid leukemia
• Diagnosis
• Immunotherapy
• Philadelphia chromosome
• Tyrosine kinase inhibitors

• BCR-ABL1
• UAS/hsp70-Gal4
• chronic myeloid leukemia (CML)
• embryonic development
• hematopoiesis
• transgenic animal model
• zebrafish

• Animals
• Animals, Genetically Modified
• Disease Models, Animal
• Humans
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics
• Zebrafish

• Acute myeloid leukemia
• decitabine
• myeloproliferative disorders
• personalized therapy
• transformed MPN

Leukemic transformation of myelodysplastic syndrome (MDS) or chronic myelogenous leukemia (CML) is a well-established phenomenon. However, co-occurrence of MDS and CML is a rare phenomenon, with few reports to date. Though blast crisis typically occurs systemically with MDS or CML, rare reports of focal transformation with myeloid sarcoma (MS) have been described. We present the first known case of concomitant MDS and CML on imatinib that developed focal blastic transformation, where the leukemic clone was BCR-ABL1 positive. Local irradiation and second-generation TKI was enough to attain long-term remission. Herein, we discuss MS and its implications in both CML and MDS.

• Myelodysplastic syndrome
• blast crisis
• chronic myelogenous leukemia
• granulocytic sarcoma
• myeloid sarcoma

Intracerebral hemorrhage (ICH) is an unusual complication in chronic myeloid leukemia (CML). Intracranial involvement, causing ICH as an initial presentation is extremely rare in CML. Herein, we reported the first case of a newly diagnosed CML patient, who presented with headaches accompanied by nausea and vomiting as the initial presentations, caused by ICH. He underwent an emergency craniotomy twice and the postoperative pathologic examination confirmed intracranial CML involvement. Interestingly, his bone marrow and cerebrospinal fluid (CSF) smear and pathological study of the involved brain tissue showed proliferation of granulocytes, which were comprised mainly of metamyelocytes and myelocytes, without any blast within the brain tissue, suggesting the stage of CML was in the chronic phase (CP). He then received dasatinib treatment and achieved complete hematologic remission in the first 3-month follow-up but failed to reach a molecular response in the 6-month follow-up. By reporting this case and reviewing relevant references, we suggested intracranial CML involvement should be considered as a potential pathogenesis of ICH when the patient presents with hyperleukocytosis. A craniotomy is mainly for intracranial decompression and benefits the diagnosis of intracranial CML involvement. Tyrosine kinase inhibitors are effective in such patients to some extent, but more appropriate treatment strategies should be investigated in further detail.

• chronic myeloid leukemia
• dasatinib
• hyperleukocytosis
• intracerebral hemorrhage
• intracranial involvement

• B cell
• B-ALL
• BCR-ABL1
• CML
• TKIs
• drug targets
• leukemia
• p190
• p210
• treatment

• Cell Lineage
• Clinical Trials as Topic
• Humans
• Leukemia/genetics
• Leukemia/pathology
• Lymphocytes/pathology
• Myeloid Cells/pathology
• Philadelphia Chromosome
• Proto-Oncogene Mas

• 2015/18/E/NZ5/00723 Narodowe Centrum Nauki
• 013/RID/2018/19 Ministerstwo Nauki i Szkolnictwa Wyższego

The digital polymerase chain reaction (dPCR) is considered to be the third-generation polymerase chain reaction (PCR), as it yields direct, absolute and precise measures of target sequences. dPCR has proven particularly useful for the accurate detection and quantification of low-abundance nucleic acids, highlighting its advantages in cancer diagnosis and in predicting recurrence and monitoring minimal residual disease, mostly coupled with next generation sequencing. In the last few years, a series of studies have employed dPCR for the analysis of hematologic malignancies. In this review, we will summarize these findings, attempting to focus on the potential future perspectives of the application of this promising technology.

• MRD monitoring
• NGS
• dPCR
• digital PCR
• hematology
• minimal residual disease
• next-generation sequencing
• somatic mutation

• Biomarkers, Tumor
• DNA Mutational Analysis
• Hematologic Neoplasms/diagnosis
• Hematologic Neoplasms/genetics
• Hematologic Neoplasms/therapy
• Hematopoietic Stem Cell Transplantation/adverse effects
• Hematopoietic Stem Cell Transplantation/methods
• High-Throughput Nucleotide Sequencing
• Humans
• Mutation
• Neoplasm, Residual/diagnosis
• Neoplasm, Residual/genetics
• Polymerase Chain Reaction/methods
• Treatment Outcome