EZH2 in normal and malignant hematopoiesis

Lund, K., Adams, P.D. and Copland, M. (2014) EZH2 in normal and malignant hematopoiesis. Leukemia, 28(1), pp. 44-49. (doi: 10.1038/leu.2013.288) (PMID:24097338)

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The histone methyltransferase Enhancer of Zeste Homologue 2 (EZH2), a component of the polycomb group complex, is vital for stem cell development, including hematopoiesis. Its primary function, to deposit the histone mark H3K27me3, promotes transcriptional repression. The activity of EZH2 influences cell fate regulation, namely the balance between self-renewal and differentiation. The contribution of aberrant EZH2 expression to tumorigenesis by directing cells toward a cancer stem cell (CSC) state is increasingly recognized. However, its role in hematological malignancies is complex. Point mutations, resulting in gain-of-function, and inactivating mutations, reported in lymphoma and leukemia, respectively, suggest that EZH2 may serve a dual purpose as an oncogene and tumor-suppressor gene. The reduction of CSC self-renewal via EZH2 inhibition offers a potentially attractive therapeutic approach to counter the aberrant activation found in lymphoma and leukemia. The discovery of small molecules that specifically inhibit EZH2 raises the exciting possibility of exploiting the oncogenic addiction of tumor cells toward this protein. However, interference with the tumor-suppressor role of wild-type EZH2 must be avoided. This review examines the role of EZH2 in normal and malignant hematopoiesis and recent developments in harnessing the therapeutic potential of EZH2 inhibition.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Lund, Dr Kirstin and Copland, Professor Mhairi and Adams, Professor Peter
Authors: Lund, K., Adams, P.D., and Copland, M.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Leukemia
ISSN (Online):1476-5551

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
506531An investigation of the control of cell division and quiescence in leukaemic versus normal haemopoietic stem and progenitor cellsMhairi CoplandScottish Executive Health Department (SEHHD-CSO)SCD/04RI CANCER SCIENCES
506532An investigation of the control of cell division and quiescence in leukaemic versus normal haemopoietic stem and progenitor cellsMhairi CoplandLeukaemia & Lymphoma Research (LRF)11017RI CANCER SCIENCES
495301Tumor progression - its antagonistic regulation by Wnt-signalling and oncogene-induced senescence.Peter AdamsCancer Research UK (CAN-RES-UK)C10652/A10250RI CANCER SCIENCES