Genomics

Dataset Information

0

Gene expression profiles of mouse BM LSKs, wild-type as well as Ezh2 KO mouse CML leukemia initiating cells (LICs)


ABSTRACT: Tyrosine kinase inhibitors (TKIs) have revolutionized chronic myelogenous leukemia (CML) management. Disease eradication, however, is hampered by innate resistance of leukemia initiating cells (LICs) to TKI-induced killing, which also provides the basis for subsequent emergence of TKI-resistant mutants. We report that EZH2, the catalytic subunit of Polycomb Repressive Complex 2 (PRC2), is overexpressed in CML LICs, required for colony formation, and survival and cell cycle progression of CML cell lines. A critical role for Ezh2 is supported by genetic studies in a mouse CML model. Inactivation of Ezh2 in conventional conditional mice and through CRISPR/Cas9-mediated gene editing prevents initiation and maintenance of disease and survival of LICs, irrespective of BCR/ABL1 mutational status, and extends survival. Expression of the Ezh2 homolog Ezh1 is reduced in Ezh2-deficient CML LICs, creating a scenario resembling complete loss of PRC2. EZH2-dependence of CML LICs raises prospects for improved therapy of TKI-resistant CML and/or eradication of disease by addition of EZH2 inhibitors.

ORGANISM(S): Mus musculus

PROVIDER: GSE85744 | GEO | 2016/08/18

SECONDARY ACCESSION(S): PRJNA339239

REPOSITORIES: GEO

Similar Datasets

2016-12-21 | GSE92624 | GEO
2018-12-11 | PXD010450 | Pride
2013-09-26 | GSE49054 | GEO
2019-08-01 | GSE132512 | GEO
2013-01-01 | GSE43225 | GEO
2023-08-30 | GSE207346 | GEO
2022-11-29 | GSE180496 | GEO
2022-07-06 | GSE177485 | GEO
2021-07-06 | GSE152706 | GEO
2021-07-06 | GSE174800 | GEO