The epigenetic landscape of T-cell acute lymphoblastic leukemia.
The genetic landscape of T-ALL has been very actively explored during the past decades. This leads to an overwhelming body of exciting novel findings providing insight into (1) the genetic heterogeneity of the disease with marked genetic subsets, (2) the mechanisms by which aberrant T-cell development drive leukemogenesis and (3) emerging opportunities for novel therapeutic interventions. Of further interest, recent genome wide sequencing studies identified proteins that actively participate in the regulation of the T-cell epigenome as novel oncogenes and tumor suppressor genes in T-ALL. The identification of these perturbed molecular epigenetic events in the pathogenesis of T-ALL will contribute to the further exploration of novel therapies in this cancer type. As some epigenetic therapies have recently been approved for a number of hematological neoplasms, one could speculate that targeted therapies against epigenetic regulators might offer good prospects for T-ALL treatment in the near future. In this review, we summarize the epigenetic discoveries made in T-ALL hitherto and discuss possible new venues for epigenetic therapeutic intervention in this aggressive subtype of human leukemia. This article is part of a Directed Issue entitled: Rare Cancers.
Center for Medical Genetics, Ghent University, Ghent, Belgium.
Joni
J
Van der Meulen
Center for Medical Genetics, Ghent University, Ghent, Belgium.
Nadine
N
Van Roy
Center for Medical Genetics, Ghent University, Ghent, Belgium.
Pieter
P
Van Vlierberghe
Center for Medical Genetics, Ghent University, Ghent, Belgium. Electronic address: franki.speleman@ugent.be.
Frank
F
Speleman
D002454:Cell Differentiation / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic; D016147:Genes, Tumor Suppressor; D015894:Genome, Human; D006657:Histones / Q000378:metabolism; D006801:Humans; D009857:Oncogenes / Q000235:genetics; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000473:pathology
D006657:Histones
DNA methylation; Epigenetics; Histone modification; Leukemia; T-ALL