To the top

Page Manager: Webmaster
Last update: 9/11/2012 3:13 PM

Tell a friend about this page
Print version

EZH2 upregulates the PI3K… - University of Gothenburg, Sweden Till startsida
To content Read more about how we use cookies on

Contact form


Note! If you want an answer on a question you must specify your email address

EZH2 upregulates the PI3K/AKT pathway through IGF1R and MYC in clinically aggressive chronic lymphocytic leukaemia

Journal article
Authors Subazini Thankaswamy Kosalai
Mohammad Hamdy Abdelrazak Morsy
N. Papakonstantinou
L. Mansouri
N. Stavroyianni
Chandrasekhar Kanduri
K. Stamatopoulos
R. Rosenquist
Meena Kanduri
Published in Epigenetics
Volume 14
Issue 11
Pages 1125-1140
ISSN 1559-2294
Publication year 2019
Published at Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
Pages 1125-1140
Language en
Keywords Chronic lymphocytic leukemia, EZH2, ChIP sequencing, PI3K pathway, IGFR1, group protein ezh2, breast-cancer, overexpression, lymphoma, target, expression, proliferation, methylation, inhibition, idelalisib, Biochemistry & Molecular Biology, Genetics & Heredity
Subject categories Biochemistry and Molecular Biology


EZH2 is overexpressed in poor-prognostic chronic lymphocytic leukaemia (CLL) cases, acting as an oncogene; however, thus far, the EZH2 target genes in CLL have not been disclosed. In this study, using ChIP-sequencing, we identified EZH2 and H3K27me3 target genes in two prognostic subgroups of CLL with distinct prognosis and outcome, i.e., cases with unmutated (U-CLL, n = 6) or mutated IGHV genes (M-CLL, n = 6). While the majority of oncogenic pathways were equally enriched for EZH2 target genes in both prognostic subgroups, PI3K pathway genes were differentially bound by EZH2 in U-CLL versus M-CLL. The occupancy of EZH2 for selected PI3K pathway target genes was validated in additional CLL samples (n = 16) and CLL cell lines using siRNA-mediated EZH2 downregulation and ChIP assays. Intriguingly, we found that EZH2 directly binds to the IGF1R promoter along with MYC and upregulates IGF1R expression in U-CLL, leading to downstream PI3K activation. By investigating an independent CLL cohort (n = 96), a positive correlation was observed between EZH2 and IGF1R expression with higher levels in U-CLL compared to M-CLL. Accordingly, siRNA-mediated downregulation of either EZH2, MYC or IGF1R and treatment with EZH2 and MYC pharmacological inhibitors in the HG3 CLL cell line induced a significant reduction in PI3K pathway activation. In conclusion, we characterize for the first time EZH2 target genes in CLL revealing a hitherto unknown implication of EZH2 in modulating the PI3K pathway in a non-canonical, PRC2-independent way, with potential therapeutic implications considering that PI3K inhibitors are effective therapeutic agents for CLL.

Page Manager: Webmaster|Last update: 9/11/2012

The University of Gothenburg uses cookies to provide you with the best possible user experience. By continuing on this website, you approve of our use of cookies.  What are cookies?