DNMT3A Harboring Leukemia-Associated Mutations Directs Sensitivity to DNA Damage at Replication Forks

Investigators showed that DNMT3A mutations underlied a defect in recovery from replication fork arrest with subsequent accumulation of unresolved DNA damage, which may have therapeutic tractability.
[Clinical Cancer Research]
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Genome-Wide Association Study Identifies Susceptibility Loci for Acute Myeloid Leukemia

Researchers performed a meta-analysis of three genome-wide association studies, with replication in a fourth study, and incorporated a total of 4018 acute myeloid leukemia (AML) cases and 10488 controls, and identified a genome-wide significant risk locus for AML at 11q13.2.
[Nature Communications]
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CD157 Signaling Promotes Survival of Acute Myeloid Leukemia Cells and Modulates Sensitivity to Cytarabine through Regulation of Anti-apoptotic Mcl-1

Investigators used peripheral blood and bone marrow samples from patients with acute myeloid leukemia (AML) to analyze the impact of CD157-directed antibodies in AML survival and in response to cytarabine ex vivo.
[Scientific Reports]
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AML with Germline DDX41 Variants Is a Clinicopathologically Distinct Entity with an Indolent Clinical Course and Favorable Outcome

Investigators demonstrated that the frequent germline pathogenic DDX41 variants characterized a clinically distinct acute myeloid leukemia (AML) entity. Features characteristic of DDX41-mutated AML included male predominance, indolent course and frequent somatic DDX41 variants.
[Leukemia]
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CD200 Expression in Hematopoietic Neoplasms: Beyond a Marker for Diagnosis of B Cell Neoplasms

Investigators review CD200 expression and its role in the immune evasion of non-B cell hematopoietic neoplasms and conclude that CD200 appears to be involved in the immune evasion of malignant cells, which could affect the survival of patients.
[Critical Reviews in Oncology Hematology]
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ALX Oncology Announces First Patient Dosed in ASPEN-05, a Phase I/II Study of Evorpacept in Combination with Venetoclax and Azacitidine in Patients with Acute Myeloid Leukemia

ALX Oncology Holdings, Inc. announced the first patient has been dosed in the Phase I/II ASPEN-05 study evaluating the combination of evorpacept with venetoclax and azacitidine for the treatment of patients with acute myeloid leukemia.
[ALX Oncology Holdings, Inc.]
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Targeting miR-126 in inv(16) Acute Myeloid Leukemia Inhibits Leukemia Development and Leukemia Stem Cell Maintenance

The authors showed that miR-126 enhanced MYC activity through the SPRED1/PLK2-ERK-MYC axis. Genetic deletion of miR-126 significantly reduced acute myeloid leukemia rate and extended survival in CBFB-MYH11 knock-in mice.
[Nature Communications]
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Regeneration of Antigen-Specific T Cells by Using Induced Pluripotent Stem Cell (iPSC) Technology

To apply the iPSC-based cell therapy in an allogeneic setting, the authors developed a method in which non-T cell-derived iPSCs were transduced with exogenous T cell receptor genes.
[International Immunology]
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Oridonin Inhibits DNMT3A R882 Mutation-Driven Clonal Hematopoiesis and Leukemia by Inducing Apoptosis and Necroptosis

Researchers performed high-throughput screening and identified that oridonin, an ent-kaurene diterpenoid extracted from the Chinese herb Rabdosia rubescens, inhibited DNMT3A R882 mutant leukemic cells at a low-micromolar concentration.
[Cell Death Discovery]
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Human Mesenchymal Stem Cells Derived Exosomes Inhibit the Growth of Acute Myeloid Leukemia Cells via Regulating miR-23b-5p/TRIM14 Pathway

TRIM14 promoted the proliferation of acute myeloid leukemia cells via activating PI3K/AKT pathway, which was reversed by human MSC-derived exosomes through delivering miR-23b-5p.
[Molecular Medicine]
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Core-Binding Factor Leukemia Hijacks the T Cell–Prone PU.1 Antisense Promoter

Researchers showed that transcriptional downregulation of PU.1 was an active process involving an alternative promoter in intron 3 that was induced by RUNX transcription factors driving noncoding antisense transcription.
[Blood]
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