• Autophagy
• Clinical applications
• Leukemia
• LncRNA
• Molecular mechanism

• Humans
• RNA, Long Noncoding/genetics
• Autophagy/genetics
• Leukemia/genetics
• Leukemia/pathology
• Signal Transduction/genetics
• Animals

• acute myeloid leukemia
• clinical biological information
• coexpression
• network analysis
• nomogram prognosis

• Humans
• Leukemia, Myeloid, Acute/genetics
• Leukemia, Myeloid, Acute/metabolism
• Leukemia, Myeloid, Acute/mortality
• Leukemia, Myeloid, Acute/pathology
• Signal Transduction
• Biomarkers, Tumor/genetics
• Biomarkers, Tumor/metabolism
• Calcineurin/metabolism
• Gene Expression Regulation, Leukemic
• Prognosis
• Computational Biology
• Protein Interaction Maps
• Gene Expression Profiling
• Databases, Genetic

• AML
• DC/DCleu-generating protocols
• anti-leukemic activity
• leukemia-derived dendritic cells

• Humans
• Dendritic Cells/immunology
• Leukemia, Myeloid, Acute/immunology
• Leukemia, Myeloid, Acute/therapy
• Leukemia, Myeloid, Acute/pathology
• Male
• Female
• Middle Aged
• Aged
• Adult
• T-Lymphocytes/immunology
• Prognosis
• Lymphocyte Culture Test, Mixed
• Granulocyte-Macrophage Colony-Stimulating Factor

• Humans
• Leukemia, Myeloid, Acute/genetics
• Leukemia, Myeloid, Acute/pathology
• Male
• Female
• Prognosis
• RNA, Long Noncoding/genetics
• Middle Aged
• Adult
• Tumor Suppressor Proteins/genetics
• Aged
• Biomarkers, Tumor/genetics
• Adolescent
• Young Adult

• AML
• DNA repair
• PARP
• immuotherapy
• synergisctic effects

• West Anhui University

• GRHL2 methylation
• acute myeloid leukemia
• diagnosis
• digital PCR
• predicting prognosis
• treatment response

• Humans
• DNA Methylation
• Leukemia, Myeloid, Acute/diagnosis
• Leukemia, Myeloid, Acute/genetics
• Prognosis
• Biomarkers
• Polymerase Chain Reaction
• DNA-Binding Proteins/genetics
• Transcription Factors/genetics

• M-2022122 Traditional Chinese Medicine Science and Technology Foundation of Shandong Province
• 81702884 National Natural Science Foundation of China
• 202111000399, 202202080721 Medicine and Health Science and Technology Foundation of Shandong Province
• ZR2022MH272, ZR2023QH115 Natural Science Foundation of Shandong Province

• acute myeloblastic leukaemia
• care pathways
• logistic regression
• population-based data
• specialised haematology unit access

• Humans
• Aged, 80 and over
• Leukemia, Myeloid, Acute/diagnosis
• Leukemia, Myeloid, Acute/epidemiology
• Leukemia, Myeloid, Acute/therapy
• Prognosis
• Cytogenetic Analysis
• Patient Care
• Hematology

• 18525 Cancer Research UK
• 29018 Cancer Research UK
• European Regional Development Fund
• Institut National du Cancer

• Humans
• Leukemia, Myeloid, Acute/genetics
• Leukemia, Myeloid, Acute/therapy
• Hematopoietic Stem Cell Transplantation/adverse effects
• Graft vs Host Disease/etiology
• Graft vs Host Disease/prevention & control
• Graft vs Leukemia Effect
• High-Throughput Nucleotide Sequencing

• AML
• NGS
• genes
• relapse
• stem cell transplant (SCT)

• Cytogenetically normal acute myeloid leukemia
• DNA methylation
• RASGEF1A
• expression
• prognosis

The clinical treatment of acute myeloid leukaemia is still dominated by chemotherapy. Clinically used anti-leukaemia drugs have shortcomings such as myelosuppression, toxicity and drug resistance. Therefore, the need to develop other chemotherapeutic drugs to meet more clinical needs is urgent. Ribonucleotide reductase (RNR) consists of a catalytic large subunit M1 (RRM1) and a regulatory small subunit M2 (RRM2), which provides dNTPs for DNA synthesis. The rapid proliferation of cancer cells requires large amounts of dNTPs. Therefore, the use of RNR inhibitors is a promising strategy for the clinical treatment of various malignancies. Monobenzone is an FDA-approved depigmenting agent for vitiligo patients. In this study, we demonstrate that monobenzone is a potent inhibitor of RNR enzyme activity by targeting RRM2 protein, and thus has significant anti-leukaemia efficacy in vitro and in vivo. This finding suggests that monobenzone has the potential to be optimized as a novel anti-AML therapeutic drug in the future.

Acute myeloid leukaemia (AML) is one of the most common types of haematopoietic malignancy. Ribonucleotide reductase (RNR) is a key enzyme required for DNA synthesis and cell proliferation, and its small subunit RRM2 plays a key role for the enzymatic activity. We predicted monobenzone (MB) as a potential RRM2 target compound based on the crystal structure of RRM2. In vitro, MB inhibited recombinant RNR activity (IC50 = 0.25 μM). Microscale thermophoresis indicated that MB inhibited RNR activity by binding to RRM2. MB inhibited cell proliferation (MTT IC50 = 6–18 μM) and caused dose-dependent DNA synthesis inhibition, cell cycle arrest, and apoptosis in AML cells. The cell cycle arrest was reversed by the addition of deoxyribonucleoside triphosphates precursors, suggesting that RNR was the intracellular target of the compound. Moreover, MB overcame drug resistance to the common AML drugs cytarabine and doxorubicin, and treatment with the combination of MB and the Bcl-2 inhibitor ABT-737 exerted a synergistic inhibitory effect. Finally, the nude mice xenografts study indicated that MB administration produced a significant inhibitory effect on AML growth with relatively weak toxicity. Thus, we propose that MB has the potential as a novel anti-AML therapeutic agent in the future.

Acute myeloid leukemia (AML) represents an aggressive hematopoietic malignancy with a prognosis inferior to that of other leukemias. Recent targeted therapies offer new opportunities to achieve better treatment outcomes. However, due to the complex heterogeneity of AML, its prognosis remains dismal. In this study, we first identified the correlation between high expression of BRD4 and overall survival of patients with AML. Targeted degradation of BRD2, BRD3, and BRD4 proteins by dBET1, a proteolysis-targeting chimera (PROTAC) against the bromodomain and extra-terminal domain (BET) family members, showed cytotoxic effects on Kasumi (AML1-ETO), NB4 (PML-RARa), THP-1 (MLL-AF9), and MV4-11 (MLL-AF4) AML cell lines representing different molecular subtypes of AML. Furthermore, we determined that dBET1 treatment arrested cell cycling and enhanced apoptosis and c-MYC was identified as the downstream target. Collectively, our results indicated that dBET1 had broad anti-cancer effects on AML cell lines with different molecular lesions and provided more benefits to patients with AML.

• Humans
• Cell Cycle Proteins/metabolism
• Cell Line, Tumor
• Intercellular Signaling Peptides and Proteins
• Leukemia, Myeloid, Acute/pathology
• Nuclear Proteins/metabolism
• Proteolysis
• Proto-Oncogene Proteins c-myc
• Transcription Factors/metabolism

• National Natural Science Foundation of China
• Natural Science Foundation of Jiangsu Province

• Acute myeloid leukemia
• Biomarker
• Circ-ANAPC7

• Apc7 Subunit, Anaphase-Promoting Complex-Cyclosome
• Biomarkers
• Humans
• Leukemia, Myeloid, Acute/diagnosis
• Leukemia, Myeloid, Acute/genetics
• Leukemia, Myeloid, Acute/metabolism
• RNA
• RNA, Circular
• ROC Curve

Relapse after allogeneic stem cell transplant in unfavorable-risk acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS) portends a poor prognosis. We conducted a single-center phase I dose-escalation study with lenalidomide maintenance in high-risk MDS and AML patients after allogeneic transplantation. Sixteen patients enrolled in a “3 + 3” study design starting at lenalidomide 5 mg daily, increasing in increments of 5 mg up to 15 mg. Lenalidomide was given for 21 days of a 28-day cycle for a total of six cycles. Most common dose-limiting toxicities were lymphopenia, diarrhea, nausea, and neutropenia. Two patients had acute graft-versus-host disease (GVHD), and five patients developed chronic GVHD. The maximum tolerated dose was 10 mg, after dose-limiting toxicities were seen in the 15 mg group. Two dose-limiting toxicities were seen from development of acute GVHD and grade III diarrhea. Limitations of the study include time to initiation at 6 months post transplant, as many high-risk patients will have relapsed within this time frame before starting maintenance lenalidomide. Overall, lenalidomide was well tolerated with minimal GVHD and low rates of relapse rates, warranting further study.

• CDK6
• acute myeloid leukemia
• invasion
• migration
• mir-148a-3p
• proliferation

• Clinical research
• Poor-risk AML
• Post-HSCT low dose azacitidine
• Post-transplantation maintenance
• Stem cell transplantation

• targeted therapies
• cancer immunotherapy
• acute myeloid leukaemia

• MiR-107
• RAD51
• acute myelocytic leukemia
• apoptosis
• interaction network

In China, for economic reasons, induction regimes for acute myeloid leukemia (AML) often involve domestically produced idarubicin (IDA) rather than imported IDA. Our objective was to compare the effectiveness of induction regimens in combination with cytarabine; involving imported or domestic IDA, or daunorubicin (DNR).

The study was conducted from 1^st July 2012 to 30^th November 2015 at Baoding No.1 Central Hospital. This was a retrospective cohort study of patients with newly diagnosed AML admitted to Baoding First Central Hospital, China. Patients were divided into three groups according to their treatment regimen: the IA-imported group, the IA-domestic group, and the DNR group. Clinical data, complete remission (CR), partial remission (PR), non-remission (NR) rates, and side effects were compared.

Total 282 patients were enrolled, including 123 patients in the IA-imported group, 98 in the IA-domestic group and 61 in the DNR group. The IA-domestic and IA-imported groups’ remission rates were similar (P=0.123) but significantly different from the DNR group (both P<0.05). Side effects were similar in all three groups and no severe side effects were reported.

Cytarabine induction regimens showed similar remission rates in combination with IDA produced in China compared to imported IDA and were more effective than DNR.

• Acute
• Daunorubicin
• Idarubicin
• Leukemia
• Myeloid
• Treatment Outcome

• acute myeloid leukemia
• bioinformatics pipeline
• biomarker
• clinical proteomics
• diagnosis
• laboratory robots
• prognosis
• treatment

• Biomarkers, Tumor/analysis
• Biomarkers, Tumor/genetics
• Biomarkers, Tumor/metabolism
• Computational Biology
• Humans
• Leukemia, Myeloid, Acute/diagnosis
• Leukemia, Myeloid, Acute/genetics
• Leukemia, Myeloid, Acute/metabolism
• Leukemia, Myeloid, Acute/therapy
• Mass Spectrometry/methods
• Prognosis
• Proteome/analysis
• Proteome/metabolism
• Proteomics/methods
• Robotics/instrumentation
• Robotics/methods
• Workflow

• cancer
• hematology
• immunotherapy
• nanotechnology

The purpose of the present study was to investigate whether expression levels of adenylate kinase 1 (AK1) were associated with prognosis of acute myeloid leukemia (AML) in patients treated with chemotherapy or allogeneic hematopoietic stem cell transplantation (allo-HSCT). 85 AML patients with AK1 expression report who received chemotherapy-alone and 71 who underwent allo-HSCT from The Cancer Genome Atlas database were identified and grouped into either AK1high or AK1low based on their AK1 expression level relative to the median. Then, overall survival (OS) and event-free survival (EFS) were compared between patients with high vs. low AK1 expression. In the chemotherapy group, high AK1 expression was favorable for both EFS (P=0.016) and OS (P=0.014). In the allo-HSCT group, there was no association for AK1 expression levels and clinical outcomes. Further analyses suggested that in the high AK1 expression group, EFS and OS were longer in patients treated with allo-HSCT compared with those treated with chemotherapy (P=0.0011; P<0.0001, respectively), whereas no significant differences were observed in the low AK1 expression group. In summary, we reported AK1 as an independent unfavorable prognostic factor of AML patients undergoing chemotherapy, and its use could also facilitate clinical decision-making in selecting treatment for AML patients. Patients with high AK1 expression may be recommended for early allo-HSCT.

• AK1
• acute myeloid leukemia
• allogeneic hematopoietic stem cell transplantation
• chemotherapy
• prognosis

• AML
• genomic screening
• myeloid sequencing panel
• next generation sequencing
• novel no-silent somatic mutation

The prognosis of children with acute monocytic leukemia (AML‐M5) remains unsatisfactory and the risk profile is still controversial. We aim to investigate the prognostic value of clinical and cytogenetic features and propose a new risk stratification in AML‐M5 children.

We included 132 children with AML‐M5. Overall survival (OS) and progression‐free survival (PFS) were documented. Cox regression was performed to evaluate the potential risk factors of prognosis.

The 5‐year‐OS was 46.0% (95% confidence intervals, 41.6%‐50.4%) in all patients. There was significantly lower OS in the age ≤ 3 years old (P = .009) and hyperleukocytosis (P < .001). The FMS‐like tyrosine kinase 3 (FLT3)‐internal tandem duplication (ITD) and MLL‐rearrangement carriers were associated with fewer survivors in all patients (37.1% and 36.7%) and chemotherapy‐only group (19.0% and 35.0%). Notably, the number of survivor with MLL‐rearrangement did not increase in hematopoietic stem cell transplant (HSCT) group. According to the Cox regression analysis, HSCT was a significantly favorable factor (P = .001), while hyperleukocytosis, age ≤ 3 years old, and BM blast ≥ 70% adversely affected the OS in all patients (all P < .05). Additionally, FLT3‐ITD was a risk factor for OS in the chemotherapy‐only group (P = .023), while hyperleukocytosis and age ≤ 3 years independently contributed to poor PFS (both P < .05). In comparison to the standard‐risk group, significant poorer outcome was found in the high‐risk group (both P < .005).

We propose that AML‐M5 children with any of MLL‐rearrangement, FLT3‐ITD, hyperleukocytosis, BM blast ≥ 70%, or age ≤ 3 years old are classified into the high‐risk group, and HSCT is beneficial especially in patients with FLT3‐ITD mutation, hyperleukocytosis, and age ≤ 3 years old. Importantly, the choice of HSCT should be made more carefully in children with MLL‐rearrangement for its suboptimal performance.

• acute monocytic leukemia
• children
• clinical characteristics
• gene mutation
• prognostic factors

Acute myeloid leukemia (AML) is a hematological cancer that mainly affects the elderly. Although complete remission (CR) is achieved for the majority of the patients after induction and consolidation therapies, nearly two-thirds relapse within a short interval. Understanding biological factors that determine relapse has become of major clinical interest in AML. We utilized liquid chromatography tandem mass spectrometry (LC-MS/MS) to identify the protein changes and protein phosphorylation events associated with AML relapse in primary cells from 41 AML patients at time of diagnosis. Patients were defined as relapse-free if they had not relapsed within a five-year clinical follow-up after AML diagnosis. Relapse was associated with increased expression of RNA processing proteins and decreased expression of V-ATPase proteins. We also observed an increase in phosphorylation events catalyzed by cyclin-dependent kinases (CDKs) and casein kinase 2 (CSK2). The biological relevance of the proteome findings was supported by cell proliferation assays using inhibitors of V-ATPase (bafilomycin), CSK2 (CX-4945), CDK4/6 (abemaciclib) and CDK2/7/9 (SNS-032). While bafilomycin preferentially inhibited the cells from relapse patients, the kinase inhibitors were less efficient in these cells. This suggests that therapy against the upregulated kinases could also target the factors inducing their upregulation rather than their activity. This study, therefore, presents markers that could help predict AML relapse and direct therapeutic strategies.

• V-ATPase
• acute myeloid leukemia
• kinase
• markers
• mass spectrometry
• patient relapse
• phosphoproteome
• proteome

• AML
• G protein
• GPCR
• Leukemia
• cell signaling
• clinical biomarkers.

• AML
• BPA
• Glycolysis
• Proliferation
• miR-15b-5p

• AML
• GVHD
• Stem cell transplantation
• T cell depletion
• Transplantation outcomes

• Adult
• Aged
• Cohort Studies
• Ethnicity/statistics & numerical data
• Female
• Follow-Up Studies
• Humans
• Leukemia, Myeloid, Acute/epidemiology
• Leukemia, Myeloid, Acute/pathology
• Leukemia, Promyelocytic, Acute/physiopathology
• Male
• Middle Aged
• New York/epidemiology
• Prognosis
• Registries/statistics & numerical data
• Survival Rate
• Young Adult

• P30 CA196521 NCI NIH HHS

• Acute myeloid leukemia
• Prognosis
• TCGA data
• miRNAs