title: Epigenetics in T-cell acute lymphoblastic leukemia.
abstract: Normal T-cell development is a strictly regulated process in which hematopoietic progenitor cells migrate from the bone marrow to the thymus and differentiate from early T-cell progenitors toward mature and functional T cells. During this maturation process, cooperation between a variety of oncogenes and tumor suppressors can drive immature thymocytes into uncontrolled clonal expansion and cause T-cell acute lymphoblastic leukemia (T-ALL). Despite improved insights in T-ALL disease biology and comprehensive characterization of its genetic landscape, clinical care remained largely similar over the past decades and still consists of high-dose multi-agent chemotherapy potentially followed by hematopoietic stem cell transplantation. Even with such aggressive treatment regimens, which are often associated with considerable side effects, clinical outcome is still extremely poor in a significant subset of T-ALL patients as a result of therapy resistance or hematological relapses. Recent genetic studies have identified recurrent somatic alterations in genes involved in DNA methylation and post-translational histone modifications in T-ALL, suggesting that epigenetic homeostasis is critically required in restraining tumor development in the T-cell lineage. In this review, we provide an overview of the epigenetic regulators that could be implicated in T-ALL disease biology and speculate how the epigenetic landscape of T-ALL could trigger the development of epigenetic-based therapies to further improve the treatment of human T-ALL.
authors.affiliation: Center for Medical Genetics, Ghent University, Ghent, Belgium.
authors.forename: Sofie
authors.initials: S
authors.lastname: Peirs
authors.forename: Joni
authors.initials: J
authors.lastname: Van der Meulen
authors.forename: Inge
authors.initials: I
authors.lastname: Van de Walle
authors.forename: Tom
authors.initials: T
authors.lastname: Taghon
authors.forename: Frank
authors.initials: F
authors.lastname: Speleman
authors.forename: Bruce
authors.initials: B
authors.lastname: Poppe
authors.forename: Pieter
authors.initials: P
authors.lastname: Van Vlierberghe
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000235:genetics; D002454:Cell Differentiation; D019070:Cell Lineage; D019175:DNA Methylation / Q000235:genetics; D044127:Epigenesis, Genetic; D006657:Histones / Q000378:metabolism; D006801:Humans; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D011499:Protein Processing, Post-Translational; D013601:T-Lymphocytes / Q000502:physiology*
chemical_list: D006657:Histones
keywords: T-ALL; epigenetics; therapeutics