Epigenetics in a Spectrum of Myeloid Diseases and Its Exploitation for Therapy
Por:
Maher, M, Diesch, J, Le Pannerer, MM and Buschbeck, M
Publicada:
1 abr 2021
Ahead of Print:
6 abr 2021
Resumen:
Simple Summary
The genome is stored in the limited space of the nucleus in a highly condensed form. The regulation of this packaging contributes to determining the accessibility of genes and is important for cell function. Genes affecting the genome's packaging are frequently mutated in bone marrow cells that give rise to the different types of blood cells. Here, we first discuss the molecular functions of these genes and their role in blood generation under healthy conditions. Then, we describe how their mutations relate to a subset of diseases including blood cancers. Finally, we provide an overview of the current efforts of using and developing drugs targeting these and related genes.
Mutations in genes encoding chromatin regulators are early events contributing to developing asymptomatic clonal hematopoiesis of indeterminate potential and its frequent progression to myeloid diseases with increasing severity. We focus on the subset of myeloid diseases encompassing myelodysplastic syndromes and their transformation to secondary acute myeloid leukemia. We introduce the major concepts of chromatin regulation that provide the basis of epigenetic regulation. In greater detail, we discuss those chromatin regulators that are frequently mutated in myelodysplastic syndromes. We discuss their role in the epigenetic regulation of normal hematopoiesis and the consequence of their mutation. Finally, we provide an update on the drugs interfering with chromatin regulation approved or in development for myelodysplastic syndromes and acute myeloid leukemia.
Filiaciones:
:
Josep Carreras Leukaemia Res Inst IJC, Canc & Leukaemia Epigenet & Biol Program, Campus Can Ruti, Badalona 08916, Spain
:
Josep Carreras Leukaemia Res Inst IJC, Canc & Leukaemia Epigenet & Biol Program, Campus Can Ruti, Badalona 08916, Spain
Germans Trias i Pujol Res Inst PMPPC IGTP, Program Predict & Personalized Med Canc, Campus Can Ruti, Badalona 08916, Spain
:
Josep Carreras Leukaemia Res Inst IJC, Canc & Leukaemia Epigenet & Biol Program, Campus Can Ruti, Badalona 08916, Spain
:
Josep Carreras Leukaemia Res Inst IJC, Canc & Leukaemia Epigenet & Biol Program, Campus Can Ruti, Badalona 08916, Spain
Germans Trias i Pujol Res Inst PMPPC IGTP, Program Predict & Personalized Med Canc, Campus Can Ruti, Badalona 08916, Spain
gold, Green Published
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