Acute Myeloid Leukemia Research

Balancing Activation and Repression: CoREST-p300 Antagonism Controls Retinoic Acid-Driven Differentiation in AML

The paper shows that Corin, a dual LSD1/CoREST inhibitor, synergizes with ATRA to induce differentiation and apoptosis in AML by disrupting CoREST-RAR/RXR complexes and recruiting p300.

Genome-wide characterization of clonal hematopoiesis reveals extensive non-coding putative driver mutations

The paper identifies novel non-coding driver mutations in clonal hematopoiesis using whole genome sequences from the UK Biobank and links them to common diseases.

MECOM is a master repressor of myeloid differentiation through dose control of CEBPA in acute myeloid leukemia

This study shows MECOM represses myeloid differentiation by inhibiting CEBPA, and its overexpression in AML reduces CEBPA levels, maintaining stem cell state.

DNMT3A-R882 mutations intrinsically drive dysfunctional neutropoiesis from human haematopoietic stem cells

This study investigates how DNMT3A-R882 mutations affect HSC differentiation into immune cells, finding they drive dysfunctional neutropoiesis linked to immune dysregulation and inflammatory disease risk.

A Rapid Gene Expression Profiler Classifies AML Tumor Responsiveness to Standard Therapies

This paper develops a rapid qPCR-based gene expression profiler to predict AML patient response to standard therapies using cell state and BCL2 family gene expression signatures.

A platform of robust patient-derived leukemia models covering subgroups for which no cell lines exist

The paper develops patient-derived AML PDX models that replicate primary AML biology and include subgroups lacking existing models, showing reduced leukemia growth after long-term chemotherapy.

Characterization of Chemoresistant Cell Populations Improves Risk Stratification and Therapy Prediction in Pediatric AML

The paper identifies chemoresistant cell populations in pediatric AML that improve risk prediction and reveal therapeutic targets for high-risk patients.

Daple-FLT3 (CCDC88C-FLT3) gene fusion requires the coiled-coil domain for maximal activation and pericentrosomal localization

This study investigates the Daple-FLT3 gene fusion, showing its constitutive kinase activity and pericentrosomal localization, with the coiled-coil domain required for maximal activation.

CEBPA repression by MECOM blocks differentiation to drive aggressive leukemias

This study identifies MECOM's role in blocking differentiation via CEBPA repression, showing that targeting this regulatory element can promote differentiation and reduce leukemia burden in AMLs.

siRNA Mediated Genetic Perturbation of Primary Human Leukemia Stem and Progenitor Cells

This study develops an efficient siRNA transfection method for primary human leukemia stem and progenitor cells, enabling effective gene knockdown and biological activity assessment.

Activation of the TP53 pathway is a therapeutic vulnerability in NUP98::KDM5A+ pediatric AML

This study identifies TRIP13 as a developmentally restricted dependency in NUP98::KDM5A+ pediatric AML, showing that its inhibition reactivates TP53 and kills leukemic cells.

Single-cell analysis of pediatric acute myeloid leukemia samples uncovers treatment-resistant stem and mast cells

This study uses single-cell RNA sequencing to identify treatment-resistant subtypes and mast cell-like cells in pediatric AML, linking them to poor outcomes.

Integrated in silico and in vitro approaches identify a HSP90 drug vulnerability axis in t(7;12) infant leukemia stem-like cells

The paper identifies HSP90 inhibitors as potential therapies for t(7;12)-AML by combining computational drug screening with in vitro experiments.

Bone marrow lymphocyte dynamics during chemotherapy in pediatric acute myeloid leukemia

This study examines lymphocyte dynamics during chemotherapy in pediatric AML, finding preserved or increased lymphocytes alongside blast reduction, suggesting a potential window for BiTE therapy.

Id1 Promotes Clonal Hematopoiesis in Mice with Tet2 Loss of Function

Genetic ablation of Id1 in Tet2-/- mice reduces clonal hematopoiesis by increasing CDKI expression, apoptosis, senescence, and differentiation while decreasing cell growth.

TP53 mutations drive therapy resistance via post-mitochondrial caspase blockade

This study identifies that TP53 mutations in AML lead to resistance to VenAza therapy by blocking caspase-3/7 activation after mitochondrial outer membrane permeabilization.

A PBD-dimer containing antibody drug conjugate targeting CCRL2 for high-risk MDS/AML

This paper develops an anti-CCRL2 antibody-drug conjugate (ADC) that shows potent cytotoxicity against high-risk MDS/AML cells without harming healthy hematopoietic cells.

CDK8 is a critical effector of cell fate dysregulation in SF3B1-mutant MDS

This study identifies CDK8 mis-splicing as a driver of altered progenitor fate in SF3B1-mutant MDS, linking splicing defects to transcriptional dysregulation and lineage commitment.

Genomic and Immunogenomic Profiling of Extramedullary Acute Myeloid Leukemia Reveals Actionable Clonal Branching and Frequent Immune Editing

This study profiles genomic and immunogenomic features of eAML, finding clonal branching and immune editing, with FLT3 mutations in relapsed cases.

Pro-inflammatory role of granzyme K producing bystander CD8+ T cells in acute myeloid leukemia

This study identifies a pro-inflammatory role of Granzyme K-producing bystander CD8+ T cells in AML, which promote IL-8 secretion and may exacerbate disease progression.

Single cell proteomics characterization of bone marrow hematopoiesis with distinct Ras pathway lesions.

The paper uses single-cell proteomics and metabolomics to study how Ras pathway mutations affect hematopoiesis, finding distinct impacts on HSC compartments and metabolism.

Differential sensitivity to LINE 1-induced damage contributes to the expansion of Tet2-deficient HSCs upon chronic inflammatory stress

The paper shows that Tet2-deficient HSCs are resistant to LPS-induced L1 derepression and genomic instability, which contributes to their clonal expansion under chronic inflammation.

Clonal hematopoiesis gene variants in South Asian Indians with premature coronary artery disease

The paper investigates the association between clonal hematopoiesis gene variants and premature coronary artery disease in South Asian Indians, finding high prevalence and specific gene variant associations.

A 3-genes interferon signature predicts sustained complete remission in pediatric AML patients

This paper identifies a three-gene interferon signature that predicts sustained remission in pediatric AML patients by stratifying chemosensitivity and survival outcomes.

Developmental Stage and Cellular Context Determine Oncogenic and Molecular Outcomes of Ezh2Y641F Mutation in Hematopoiesis

This study shows that the Ezh2Y641F mutation causes different outcomes in hematopoiesis depending on developmental stage and cell type, leading to either bone marrow failure or lymphoma.

The HOTAIRM1-miR-222 Axis Regulates Venetoclax Resistance and Defines a High-Risk Subset in Pediatric t(8;21) Acute Myeloid Leukemia

The paper identifies HOTAIRM1-miR-222 axis as a regulator of venetoclax resistance and a marker of high-risk t(8;21) AML in pediatric patients.

Chemoresistance of TP53 mutant AML requires the mevalonate byproduct, GGPP, for regulation of ROS and induction of a mitochondria stress response

This study identifies GGPP, a mevalonate pathway byproduct, as critical for chemoresistance in TP53mut AML through ROS regulation and mitochondria stress response, suggesting statin-based therapies could be effective.

RNA expression data suggest ALDH2 inhibition as a concept for killing acute myeloid leukemia cells that are resistant to ALDH1 inhibitors: the example of NPM1 mutant AML

The paper analyzes RNA expression data to show that ALDH2 is more prognostically significant than ALDH1A1 in NPM1 mutant AML, suggesting ALDH2 inhibition as a potential therapeutic strategy.

Age-Dependent Increase and Dysregulation of the Splicing Machinery in Acute Myeloid Leukemia of Older Patients

This study identifies age-related dysregulation of the splicing machinery in older AML patients through proteomic analysis, highlighting potential targets for age-specific therapies.

Clonal evolution of hematopoietic stem cells after cancer chemotherapy

This study examines how chemotherapy affects clonal diversity and mutation patterns in hematopoietic stem cells, finding that melphalan increases mutational burden and promotes clonal aging, potentially leading to therapy-related myeloid neoplasms.