DNA metiltransferases nas neoplasias hematológicas – síndrome mielodisplásica e leucemia
mieloide aguda
DNA methyltransferases in hematologic malignancies.
Li KK(1), Luo LF, Shen Y, Xu J, Chen Z, Chen SJ.
Semin Hematol. 2013 Jan;50(1):48-60. doi:
10.1053/j.seminhematol.2013.01.005.
Author information:
(1)State Key Laboratory of Medical Genomics, Shanghai Institute of
Hematology, Rui
Jin Hospital Affiliated to Shanghai JiaoTong University School of
Medicine,
Shanghai, China.
DNA methyltransferases (DNMTs) are the key enzymes for
genome methylation, which plays an important role in
epigenetically regulated gene expression and repression.
Mouse models with conditional knockout of the DNA
methyltransferase 1 (DNMT1) and DNA methyltransferase 3A
(DNMT3A) genes have revealed a role of DNA methylation in
mediating the self-renewal and differentiation of normal
hematopoietic stem cells (HSCs) and the leukemia stem cells
(LSCs). Recently, various mutations of DNMT3A and other DNA
methylation regulators have been identified in hematologic
malignancies. Functional analysis of these mutations
may lead to a better understanding of the disease mechanisms,
and even the discovery of new biomarkers and/or drug targets,
as well as more rational design of therapeutic regimens.
Moreover, DNMTs inhibitors as epigenetic drugs have already
been approved by US Food and Drug Administration for clinical
use and some clinical trials are currently underway in
patients with myelodysplastic syndromes (MDS) and acute
myeloid leukemia (AML). This review focuses on the
biology of DNMTs with regard to epigenetic regulation, HSC
renewal/differentiation, and drug discovery for targeted
therapy, and delineates the latest studies that have been
conducted to unfold the relationship between aberrant DNMTs
and hematologic malignancies.
Copyright © 2013 Elsevier Inc. All rights reserved.
PMID: 23507483