Acute Myeloid Leukemia Research

Strategies for Overcoming the Purification Challenges of Meis1 and HoxA9 and Their Functional Characterization

This study optimizes the purification of Meis1 and HoxA9 proteins and characterizes their DNA-binding and cooperative interactions.

Persistent Malignant Stem Cells Drive Relapse After Transplantation in the Myelodysplastic Neoplasms

The paper detects malignant hematopoietic stem cells (HSCs) in myelodysplastic neoplasms (MDS) using low-input sequencing and shows they predict relapse after transplantation.

Choline Kinase Alpha Inhibition is a Mutation Agnostic Therapeutic Vulnerability in Clonal Hematopoiesis

This study identifies CHKA/PAF metabolic dependency in clonal hematopoiesis across multiple mutations and shows its suppression reduces clonal expansion.

The genetic, clinical and immune landscape of clonal hematopoiesis across adulthood in the multi-ancestry Mount Sinai Million cohort

This study characterizes clonal hematopoiesis across adulthood and genetic ancestry in a large cohort, finding age-related increases in prevalence, ancestry-specific differences, and associations with immune markers and disease outcomes.

Recurrent leukaemia stem cell states define the antigenic landscape of paediatric Acute Myeloid Leukaemia

This study identifies three leukaemia stem cell subtypes in paediatric AML and shows that combining CLEC12A and CD84 targets all subtypes while sparing healthy cells.

Coordination of cell cycle and hematopoietic differentiation by a HoxA9/Myc/Cdk6 feedback loop

This study identifies a HoxA9/Myc/Cdk6 feedback loop that coordinates cell cycle and hematopoietic differentiation through transcriptional and post-translational mechanisms.

A scalable in vitro cell competition model identifies preleukemic super competitor clones

This study develops an in vitro clonal competition model to identify preleukemic TET2-mutant clones that suppress wild-type cells through RAC1-GEF signalling inhibition.

Development and pharmacological characterization of a stable HEK293 cell model for the study of human FLT3 signaling and its pharmacological modulation

The paper develops a stable HEK293 cell line expressing FLT3 for pharmacological studies and shows it effectively models FLT3 signaling and response to inhibitors.

Venetoclax Resistance Creates Canonical Pyroptosis Vulnerability in AML

This study shows that venetoclax resistance in AML creates a vulnerability to canonical pyroptosis, which can be targeted with DPP8/9 inhibitors and NLRP3 activators.

Artificial Intelligence Applied to Epigenomic Data in Leukemia: A Systematic Review of Diagnostic, Prognostic and Monitoring Models

This paper reviews AI models using epigenomic data for leukemia diagnosis, prognosis, and monitoring, finding high accuracy in classification but limited external validation and prospective testing.

CBFA2T3-GLIS2 establishes transcriptionally permissive enhancer hypermethylation associated with venetoclax response in pediatric AML

The paper identifies enhancer hypermethylation as a feature of C/G AML linked to venetoclax response and shows DNMT3B inhibition enhances treatment efficacy.

Novel RNA Polymerase I and Cyclin Dependent Kinase combination therapy for the treatment of aggressive Acute Myeloid Leukemia.

This paper identifies a synergistic combination of RNA Polymerase I inhibitor CX-5461 and CDK inhibitor Dinaciclib that enhances therapeutic efficacy in AML by inducing nucleolar stress and cell cycle arrest.

Sensitivity to ATR-CHK1 pathway inhibition in AML/MDS is enhanced by SRSF2 mutations and reduced by RUNX1 loss

This study identifies SRSF2 and U2AF1 mutations as biomarkers of sensitivity to ATR-CHK1 pathway inhibitors and RUNX1 mutations as a mechanism of resistance in MDS/AML.

TET loss of function selects for aneuploidies that confer a proliferative advantage

This study shows that TET loss of function promotes aneuploidy, particularly chromosome 17 trisomy, which provides a proliferative advantage in iNKT cells and mESCs.

Exploiting an Epigenetic Resistance Mechanism to PI3 Kinase Inhibition in Leukemic Stem Cells

This study identifies a resistance mechanism in AML leukemic stem cells to PI3K inhibition and shows that combining PI3K and EZH1/2 inhibitors overcomes resistance.

Somatic DDX41 mutations confer neomorphic splicing activity in the pathogenesis of myelodysplastic neoplasms

This study identifies somatic DDX41 mutations as gain-of-function alleles that drive aberrant splicing, particularly of SEPTIN7, contributing to MDS/AML pathogenesis.

A CRISPR-Based Humanized Model Reveals Cooperative Role of STAG2 Loss in Familial GATA2-Deficient MDS Progression

This paper uses a CRISPR-based humanized model to show that STAG2 loss cooperates with GATA2 deficiency to drive MDS progression through increased HSC self-renewal and myeloid bias.

Chemical Proteomics of Residual Acute Myeloid Leukemia Cells Reveals Therapeutic Vulnerabilities

This study uses CoPISA and proteomics to analyze venetoclax-azacitidine response in AML cells, identifying adaptive vulnerabilities like NRP2.

Biomarker-Targeted O6-Guanine Alkylation Potentiates ATR Inhibitor Response in De Novo and Relapsed/Refractory AML

This study identifies MGMT silencing as a therapeutic target in AML and shows that combining O6-fluoroethylating agents with ATR inhibitors improves treatment outcomes.

H3-K27M mutation alters the dynamics of human hematopoietic stem cells and delays erythroid differentiation

This study shows that the H3-K27M mutation alters hematopoietic stem cell dynamics and erythroid differentiation, increasing blood cell numbers despite impaired maturation.

(E,E)-bisantrene suppresses MYC expression and displays anti-leukemic activity in acute myeloid leukemia

This study evaluates (E,E)-bisantrene's anti-leukemic activity in AML by showing it suppresses MYC expression and induces apoptosis across multiple models.

Glucocorticoids reprogram human AML leukemic stem cells to promote elimination through differentiation and apoptosis

This study shows glucocorticoids eliminate AML leukemic stem cells by inducing differentiation and apoptosis, with mechanisms involving the glucocorticoid receptor and inflammatory signatures.

The sensitivity of acute myeloid leukemia to CDK8/19 inhibitors is determined by their metabolic profile

This study identifies that acute myeloid leukemia (AML) sensitivity to CDK8/19 inhibitors is linked to their metabolic profile, specifically glycolytic activity and TCA disruption.

A combined program of induced stemness and differentiation in response to interferon gamma drives acute myeloid leukaemia growth

The paper shows that IFNg induces both stemness and differentiation in AML cells, leading to heterogeneous responses that affect leukemia growth and regeneration.

Discovery of compounds targeting human acute myeloid leukemia stem cells via a novel high-throughput screen

This study identifies compounds targeting human AML stem cells through a high-throughput screen and validates their efficacy using xenotransplantation and single-cell RNA sequencing.

A Step-wise, Deterministic and Fatal Mouse Model of Myeloid Neoplasm with Spontaneous Acquisition of Patient-relevant RTK-RAS Mutations

This study creates a mouse model of myeloid neoplasm with spontaneous RTK-RAS mutations, showing a premalignant phase and lineage restriction in tumors.

Multi-hit STAG2 mutations define a high-risk subset of MDS and reveal convergent evolutionary targeting of cohesin

The paper identifies multi-hit STAG2 mutations in MDS patients, showing they are associated with worse outcomes and suggest convergent evolutionary targeting of the cohesin gene.

Age-related clonal hematopoiesis and mosaic sex chromosome loss define distinct systemic proteomic programs and disease vulnerabilities

The paper examines age-related clonal hematopoiesis and mosaic sex chromosome loss in UK Biobank participants, finding distinct proteomic programs and disease associations for each.

Cheminformatic identification of small molecules targeting acute myeloid leukemia

The paper identifies small molecules targeting AML by screening for compounds with predicted functions in apoptosis, glutathione metabolism, and autophagy, validating their efficacy in AML cells and patient-derived samples.

A PTBP1-CDC42 splicing axis regulates leukemia growth and venetoclax sensitivity in acute myeloid leukemia

This study identifies PTBP1-CDC42 splicing regulation as a critical factor in AML growth and venetoclax sensitivity, suggesting a therapeutic combination strategy.