Explanipedia

BCOR Mutations Define a Therapeutic Vulnerability to DHODH Inhibition in Acute Myeloid Leukemia Open

F. Robert, Cherif Badja, Soraya Boushaki, Andrea Degasperi, Yasin Memari , et al. · 2025

Acute Myeloid Leukemia (AML) remains challenging to treat, especially in cases with mutations in the BCL-6 co-repressor (BCOR), which are associated with poor prognosis and chemo-resistance. In this study, we reveal a synthetic lethal inte…

Telomere attrition becomes an instrument for clonal selection in aging hematopoiesis and leukemogenesis Open

Matthew McLoughlin, Sruthi Cheloor Kovilakam, William G. Dunn, Muxin Gu, Jake Tobin , et al. · 2025

The mechanisms through which mutations in splicing factor genes drive clonal hematopoiesis (CH) and myeloid malignancies, and their close association with advanced age, remain poorly understood. Here we show that telomere maintenance plays…

Posttranscriptional depletion of ribosome biogenesis factors engenders therapeutic vulnerabilities in NPM1-mutant AML Open

Aristi Damaskou, Rachael Wilson, Malgorzata Gozdecka, George Giotopoulos, Ryan Asby , et al. · 2025

NPM1 is a multifunctional phosphoprotein with key roles in ribosome biogenesis among its many functions. NPM1 gene mutations drive 30% of acute myeloid leukemia (AML) cases. The mutations disrupt a nucleolar localization signal and create …

Mitochondrial metabolism sustains DNMT3A-R882-mutant clonal haematopoiesis Open

Malgorzata Gozdecka, Monika Dudek, Sean Wen, Muxin Gu, Richard J Stopforth , et al. · 2025

Somatic DNMT3A -R882 codon mutations drive the most common form of clonal haematopoiesis (CH) and are associated with increased acute myeloid leukaemia (AML) risk 1,2 . Preventing expansion of DNMT3A -R882-mutant haematopoietic stem/progen…

DNA polymerase theta-mediated DNA repair is a functional dependency and therapeutic vulnerability in DNMT3A deficient leukemia cells Open

Bac Viet Le, Umeshkumar Vekariya, Monika M. Toma, Margaret Nieborowska-Skorska, Marie‐Christine Caron , et al. · 2024

Myeloid malignancies carrying somatic DNMT3A mutations (DNMT3Amut) are usually resistant to standard therapy. DNMT3Amut leukemia cells accumulate toxic DNA double strand breaks (DSBs) and collapsed replication forks, rendering them depende…

Preleukemic single-cell landscapes reveal mutation-specific mechanisms and gene programs predictive of AML patient outcomes Open

Tomoya Isobe, Iwo Kuciński, Melania Barile, Xiaonan Wang, Rebecca Hannah , et al. · 2023

P1334: THE IMPACT OF SMALL MOLECULE INHIBITION OF METTL3 ON NORMAL HAEMATOPOIESIS Open

Katherine Sturgess, M. S. Vijayabaskar, Eliza Yankova, Justyna Rak, Maria Eleftheriou , et al. · 2023

Topic: 23. Hematopoiesis, stem cells and microenvironment Background: Targeting RNA methylation by selective catalytic inhibition of the RNA methyltransferase METTL3 has shown significant promise as a therapeutic strategy against AML. Whil…

Pharmacological inhibition of METTL3 impacts specific haematopoietic lineages Open

Katherine Sturgess, Eliza Yankova, M. S. Vijayabaskar, Tomoya Isobe, Justyna Rak , et al. · 2023

Transcriptional variability accelerates preleukemia by cell diversification and perturbation of protein synthesis Open

Shikha Gupta, Oliver M. Dovey, Ana Filipa Domingues, Oliwia W. Cyran, Caitlin M. Cash , et al. · 2022

Transcriptional variability facilitates stochastic cell diversification and can in turn underpin adaptation to stress or injury. We hypothesize that it may analogously facilitate progression of premalignancy to cancer. To investigate this,…

Publisher Correction: UTX-mediated enhancer and chromatin remodeling suppresses myeloid leukemogenesis through noncatalytic inverse regulation of ETS and GATA programs Open

Malgorzata Gozdecka, Eshwar Meduri, Milena Mazan, Konstantinos Tzelepis, Monika Dudek , et al. · 2022

Transcriptional variability accelerates pre-leukemia by cell diversification and perturbation of protein synthesis Open

Shikha Gupta, Oliver M. Dovey, Ana Filipa Domingues, Oliwia W. Cyran, Caitlin M. Cash , et al. · 2021

Transcriptional variability facilitates stochastic cell diversification and can in turn underpin adaptation to stress or injury. We hypothesize that it may analogously facilitate progression of pre-malignancy to cancer. To investigate this…

Mutational synergy during leukemia induction remodels chromatin accessibility, histone modifications and three-dimensional DNA topology to alter gene expression Open

Haiyang Yun, Nisha Narayan, Shabana Vohra, George Giotopoulos, Annalisa Mupo , et al. · 2021

SETBP1 overexpression acts in the place of class-defining mutations to drive FLT3-ITD–mutant AML Open

Suruchi Pacharne, Oliver M. Dovey, Jonathan Cooper, Muxin Gu, Mathias Friedrich , et al. · 2021

Advances in cancer genomics have revealed genomic classes of acute myeloid leukemia (AML) characterized by class-defining mutations, such as chimeric fusion genes or in genes such as NPM1, MLL, and CEBPA. These class-defining mutations fre…

Small-molecule inhibition of METTL3 as a strategy against myeloid leukaemia Open

Eliza Yankova, Wesley Blackaby, Mark R. Albertella, Justyna Rak, Étienne De Braekeleer , et al. · 2021

KAT7 is a genetic vulnerability of acute myeloid leukemias driven by MLL rearrangements Open

Yan Zi Au, Muxin Gu, Étienne De Braekeleer, Malgorzata Gozdecka, Demetrios Aspris , et al. · 2020

KAT7 is a therapeutic vulnerability ofMLL-rearranged acute myeloid leukemia Open

Yan Zi Au, Muxin Gu, Étienne De Braekeleer, Jason Yu, Swee Hoe Ong , et al. · 2020

Histone acetyltransferases (HATs) catalyze the transfer of an acetyl group from acetyl-CoA to lysine residues of histones and play a central role in transcriptional regulation in diverse biological processes. Dysregulation of HAT activity …

Mutational synergy coordinately remodels chromatin accessibility, enhancer landscape and 3-Dimensional DNA topology to alter gene expression during leukemia induction Open

Haiyang Yun, Shabana Vohra, Annalisa Mupo, George Giotopoulos, Daniel Sasca , et al. · 2020

Altered transcription is a cardinal feature of acute myeloid leukemia (AML), however, exactly how mutations synergize to remodel the epigenetic landscape and rewire 3-Dimensional (3-D) DNA topology is unknown. Here we apply an integrated g…

Contrasting requirements during disease evolution identify EZH2 as a therapeutic target in AML Open

Faisal Basheer, George Giotopoulos, Eshwar Meduri, Haiyang Yun, Milena Mazan , et al. · 2019

Epigenetic regulators, such as EZH2, are frequently mutated in cancer, and loss-of-function EZH2 mutations are common in myeloid malignancies. We have examined the importance of cellular context for Ezh2 loss during the evolution of acute …

SRPK1 maintains acute myeloid leukemia through effects on isoform usage of epigenetic regulators including BRD4 Open

Konstantinos Tzelepis, Étienne De Braekeleer, Demetrios Aspris, Isaia Barbieri, M. S. Vijayabaskar , et al. · 2018

UTX-mediated enhancer and chromatin remodeling suppresses myeloid leukemogenesis through noncatalytic inverse regulation of ETS and GATA programs Open

Malgorzata Gozdecka, Eshwar Meduri, Milena Mazan, Konstantinos Tzelepis, Monika Dudek , et al. · 2018

A CRISPR Dropout Screen Identifies Genetic Vulnerabilities and Therapeutic Targets in Acute Myeloid Leukemia Open

Konstantinos Tzelepis, Hiroko Koike-Yusa, Étienne De Braekeleer, Yilong Li, Emmanouil Metzakopian , et al. · 2016

Acute myeloid leukemia (AML) is an aggressive cancer with a poor prognosis, for which mainstream treatments have not changed for decades. To identify additional therapeutic targets in AML, we optimize a genome-wide clustered regularly inte…

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