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Epigenetic alterations in hematopoietic malignancies
Ist Teil von
International journal of hematology, 2012-10, Vol.96 (4), p.413-427
Ort / Verlag
Japan: Springer Japan
Erscheinungsjahr
2012
Quelle
MEDLINE
Beschreibungen/Notizen
Gene discovery efforts in patients with hematopoietic malignancies have brought to the forefront a series of mutations in genes thought to be involved in the epigenetic regulation of gene transcription. These mutations occur in genes known, or suspected, to play a role in modifying cytosine nucleotides on DNA and/or altering the state of histone modifications. Genes such as
ASXL1
,
DNMT3A
,
EZH2
,
IDH1
/
2
,
MLL1
, and
TET2
all have been shown to be mutated and/or translocated in patients with myeloid malignancies. Intriguingly, many of the alterations affecting DNA cytosine modifications in myeloid malignancies (mutations in
DNMT3A
,
IDH1
/
2
, and
TET2
) have also been found in patients with T-cell lymphomas, and
EZH2
mutations appear to be critical in T-cell acute lymphoblastic leukemia development as well. In addition, the discovery of frequent mutations in
CREBBP
,
EP300
,
EZH2
, and
MLL2
in B-cell lymphomas suggests that epigenetic alterations play a critical role in lymphomagenesis. The purpose of this review is to present functional evidence of how alterations in these epigenetic modifiers promote hematopoietic transformation. The conclusions drawn from these data are valuable in understanding biological mechanisms and potential therapeutic targets.