Epigenetics in Hematologic Malignancies
Guest Editor: Dr. E Estey
“Epigenetics” refers to changes in the gene expression occurring without alterations in DNA sequence. Accumulating evidence indicates that epigenetic abnormalities may underlie the pathogenesis of many types of leukemia. Accordingly targeting these abnormalities is a very plausible approach to leukemia therapy. These possibilities have prompted Leukemia to publish an “Epigenetics in Hematologic Malignancies” Spotlight series. The papers in the series range from the more “basic” to the more “clinical”.
So far Abdel-Wahab and Dey discuss how ASXL1 and BAP1 coordinate to regulate several epigenetic pathways. AXSL1 mutations occur in a wide range of myeloid malignancies and are often associated with poor prognosis while BAP1 is likely a tumor suppressor whose deletion results in a CMML phenotype. In a subsequent paper in the series Schoofs , Berdel, and Mueller-Tidow describe possible origins of the distinctive albeit aberrant methylation profiles that characterize various molecular subtypes of AML. Later in the series, Koh et al. elucidate their work on the physical and functional interactions between RUNX1 and MLL, among the most frequently altered genes in acute leukemia, and the consequences of these interactions for epigenetic regulation of hematopoietic genes. Focusing on specific myeloid diseases Itzykson and Fenaux provide an overview of the origin and role of epigenetic aberrations in MDS pathogenesis and the mechanism of action of “hypomethylating agents” (HMA), the most active drugs in advanced MDS, while Solary et al. describe epigenetic changes and their implications in myeloproliferative neoplasms (MPN), and Estey discusses clinical trials of HMA in AML.
More articles to be added soon.
20142013
2014
The mechanistic role of DNA methylation in myeloid leukemogenesis
J Jasielec, V Saloura and L A Godley
Leukemia 28: 1765-1773; Published online, 20 May 2014; doi:10.1038/leu.2014.163
Chromatin modifiers and the promise of epigenetic therapy in acute leukemia Open
S M Greenblatt and S D Nimer
Leukemia 28: 1396-1406; Published online, 10 March 2014; doi:10.1038/leu.2014.94
2013
The Ten-Eleven Translocation-2 (TET2) gene in hematopoiesis and hematopoietic diseases
E Solary, O A Bernard, A Tefferi, F Fuks and W Vainchenker
Leukemia 28: 485-496; Published online, 13 November 2013; doi:10.1038/leu.2013.337
The ASXL–BAP1 axis: new factors in myelopoiesis, cancer and epigenetics FREE
O Abdel-Wahab and A Dey
Leukemia 27: 10-15; Published online, 09 October 2012; doi:10.1038/leu.2012.288
RUNX1 meets MLL: epigenetic regulation of hematopoiesis by two leukemia genes FREE
C P Koh, C Q Wang, C E L Ng, Y Ito, M Araki, V Tergaonkar, G Huang and M Osato
Leukemia 27: 1793-1802; Published online, 02 July 2013; doi:10.1038/leu.2013.200
Epigenetics in clinical practice: the examples of azacitidine and decitabine in myelodysplasia and acute myeloid leukemia FREE
E H Estey
Leukemia 27: 1803-1812; Published online, 12 June 2013; doi:10.1038/leu.2013.173
Origins of aberrant DNA methylation in acute myeloid leukemia
T Schoofs, W E Berdel and C Müller-Tidow
Leukemia 28: 1-14; Published online, 20 August 2013; doi:10.1038/leu.2013.242