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identifier PRJDB2389
type bioproject
sameAs
sra-study  DRP000512
organism Mus musculus
title Ezh2 augments leukemogenecity by reinforcing differentiation block in acute myeloid leukemia.
description EZH2, a catalytic component of the polycomb repressive complex (PRC) 2, trimethylates histone H3 at lysine 27 (H3K27) to repress the transcription of target genes. Although EZH2 is overexpressed in various cancers including hematological malignancies, the role of EZH2 in acute myeloid leukemia (AML) remained to be determined. In this study, we transformed granulocyte macrophage progenitors (GMPs) from Cre-ERT;Ezh2flox/flox mice with the MLL-AF9 leukemic fusion gene and analyzed function of Ezh2 in AML. Deletion of Ezh2 in transformed GMPs severely compromised growth in vitro and significantly attenuated the progression of leukemia in vivo. Notably, Ezh2-deficient AML cells showed an obvious tendency of differentiation, had lower frequency of leukemia-initiating cells, and developed leukemia mimicking chronic myelomonocytic leukemia. Chromatin immunoprecipitation followed by sequencing analyses revealed a significant reduction in levels of trimethylation at H3K27 in Ezh2-deficient AML cells not only at Ink4a/Arf, its known major target, but also at a cohort of genes relevant to the developmental and differentiation processes. De-repressed genes in Ezh2-deficient AML cells included a gene that can promote differentiation of control AML cells. Our findings suggest that Ezh2 keeps differentiation programs poised for activation in leukemic stem cells, thereby augmenting their leukemogenic capacity. Role of Ezh2 in acute myeloid leukemia.
data type DDBJ SRA Study
publication
22677129
external link
properties 
{...}
dbXrefs
sra-run  DRR001712
sra-submission  DRA000488
biosample  SAMD00010880
sra-study  DRP000512
sra-sample  DRS001166
sra-experiment  DRX001181
distribution JSONJSON-LD
status public
visibility unrestricted-access
dateCreated 2014-05-12T00:46:27+0000
dateModified 2014-05-12T00:46:27+0000
datePublished 2014-05-12T00:46:27+0000