Acute Myeloid Leukemia Research

Discovering the drivers of clonal hematopoiesis

The paper identifies genes driving clonal hematopoiesis by analyzing somatic mutations in blood samples from cancer cohorts, discovering novel candidates and recovering known drivers.

Transcriptional plasticity drives leukemia immune escape

The paper identifies transcription factors regulating MHC-II expression in AML and shows their role in immune evasion and relapse.

Clonal dynamics of haematopoiesis across the human lifespan

This study tracks clonal dynamics in human haematopoiesis across age, finding that clonal diversity sharply declines after 70, driven by positive selection on many genes and loss of Y chromosome in males.

Cost effective sequencing enables longitudinal profiling of clonal hematopoiesis

The paper develops a cost-effective sequencing assay to detect clonal hematopoiesis and shows that most clonal mutations expand over time in longitudinal samples.

Allelic Complexity of KMT2A Partial Tandem Duplications in Acute Myeloid Leukemia and Myelodysplastic Syndromes

This study identifies secondary genetic events in KMT2A-PTD patients, showing their association with disease progression and higher RNA expression.

A distinct core regulatory module enforces oncogene expression in KMT2A-rearranged leukemia

The paper identifies a modular core regulatory circuitry in AML that enforces oncogene expression in KMT2A-rearranged leukemias.

Clinical Utility of Combined Optical Genome Mapping and 523-gene Next Generation Sequencing Panel For Comprehensive Evaluation of Myeloid Cancers.

This study evaluates the clinical utility of optical genome mapping and a 523-gene NGS panel for comprehensive genomic profiling of myeloid cancers, showing higher sensitivity and resolution compared to standard-of-care methods.

Increased CHIP Prevalence Amongst People Living with HIV

The paper investigates the prevalence of clonal hematopoiesis of indeterminate potential (CHIP) in people living with HIV and finds a higher prevalence compared to controls.

Exome sequencing of 628,388 individuals identifies common and rare variant associations with clonal hematopoiesis phenotypes

This study uses exome sequencing of 628,388 individuals to identify genetic variants associated with clonal hematopoiesis and its health outcomes.

Clonal hematopoiesis in individuals with ANKRD26 or ETV6 germline mutations

This study examines clonal hematopoiesis risk in individuals with germline ANKRD26 or ETV6 mutations, finding that ANKRD26 carriers have elevated risk while ETV6 carriers do not.

Kdm6a Deficiency Restricted to Mouse Hematopoietic Cells Causes an Age- and Sex-dependent Myelodysplastic Syndrome-Like Phenotype

This study shows that Kdm6a deficiency in mouse hematopoietic cells leads to age- and sex-dependent myelodysplastic syndrome-like features without overt leukemia.

Genome-wide association study identifies susceptibility loci for acute myeloid leukemia

This study identifies two genome-wide significant susceptibility loci for acute myeloid leukemia through a meta-analysis of GWAS data.

Genome-wide association analyses identify variants in IRF4 associated with acute myeloid leukemia and myelodysplastic syndrome susceptibility

This study identifies IRF4 variants associated with increased risk of de novo AML and MDS through GWAS and TWAS analyses using the DISCOVeRY-BMT cohorts.

Utilizing proteomics and phosphoproteomics to predict ex vivo drug sensitivity across genetically diverse AML patients

The paper predicts ex vivo drug sensitivity in AML patients using proteomic and phosphoproteomic signatures, showing better accuracy than mutation or mRNA-based signatures.

Expansion of mutation-driven haematopoietic clones is associated with insulin resistance and low HDL-cholesterol in individuals with obesity

The paper shows that in individuals with obesity, mutation-driven haematopoietic clones grow faster with insulin resistance and low HDL-C, which are cardiovascular risk factors.

Alternative splicing redefines landscape of commonly mutated genes in acute myeloid leukemia

The paper shows that alternative splicing contributes to gene disruption in AML, increasing the number of patients with functional gene loss beyond what is detected by mutations alone.

Identification of leukemic and pre-leukemic stem cells by clonal tracking from single-cell transcriptomics

The paper identifies and profiles leukemic and pre-leukemic stem cells using single-cell transcriptomics combined with lineage tracing via somatic variants.

Frequency and Prognostic Value of NPM1 Mutations in Sudanese Acute Myeloid Leukemia Patients

This study examines NPM1 mutations in Sudanese AML patients and finds no mutations, indicating all patients have wild-type NPM1.

Patient-tailored design of AML cell subpopulation-selective drug combinations

This paper develops a computational-experimental approach to design patient-specific drug combinations for AML that are synergistic and minimally toxic.

Different mutant RUNX1 oncoproteins program alternate haematopoietic differentiation trajectories

The paper shows that different RUNX1 mutations alter gene regulatory networks and chromatin programming, leading to distinct hematopoietic differentiation trajectories and disease phenotypes.

Definition of a Small Core Transcriptional Circuit Regulated by AML1-ETO

The paper defines a small core transcriptional circuit regulated by AML1-ETO using CRISPR-based degradation and transcriptomic analysis.

Expression of ERV3-1 in Leukocytes of Acute Myelogenous Leukemia Patients

The paper analyzes expression of 12 retroviral-like genes in AML patients and finds ERV3-1 is highly expressed in myeloid lineage cells, potentially linked to chromosome 8 trisomy.

A National Multicenter Evaluation of the Clinical Utility of Optical Genome Mapping for Assessment of Genomic Aberrations in Acute Myeloid Leukemia

This study evaluates optical genome mapping (OGM) for detecting genomic aberrations in AML, finding it identifies all clinically relevant SVs and CNVs and detects additional variants missed by standard methods.

Implications of TP53 Allelic State for Genome Stability, Clinical Presentation and Outcomes in Myelodysplastic Syndromes

The paper examines TP53 allelic states in MDS patients, finding that bi-allelic targeting is linked to worse outcomes, while mono-allelic targeting does not differ from wild-type patients.

Endogenous retroviruses are a source of enhancers with oncogenic potential in acute myeloid leukemia

The paper identifies endogenous retroviruses (ERVs) as a source of oncogenic enhancers in acute myeloid leukemia (AML) and shows their role in altering gene expression and promoting cell growth.

Loss of Tet2 affects proliferation and drug sensitivity through altered dynamics of cell-state transitions

This study shows that Tet2 loss-of-function in AML cells alters cell-state transitions, improving survival during drug treatment and contributing to relapse.

Monogenic and polygenic inheritance become instruments for clonal selection

The paper identifies inherited and acquired genetic variants that increase susceptibility to clonal hematopoiesis by influencing clonal selection through monogenic and polygenic mechanisms.

Histopathological Landscape of Molecular Genetics and Clinical Determinants in MDS Patients

This study uses deep learning to analyze bone marrow histopathology in MDS patients, linking morphological features to genetic and clinical outcomes.

Clinical Laboratory Validation and Implementation of Quantitative, Real-Time PCR-based Monitoring of NPM1 Type A Mutation

This paper validates and implements a quantitative real-time PCR method for monitoring NPM1 Type A mutations in AML, showing it is sensitive and reproducible for clinical use.

Recurrent pre-leukemic deletions in myeloid malignancies are the result of DNA double-strand breaks followed by microhomology-mediated end joining

The paper identifies microhomology-mediated end joining (MMEJ) as the mechanism behind recurrent deletions in myeloid malignancies and shows that these deletions occur in multipotent hematopoietic stem cells.