Journal article

MOZ regulates B-cell progenitors and, consequently, Moz haploinsufficiency dramatically retards MYC-induced lymphoma development

BN Sheikh, SCW Lee, F El-Saafin, HK Vanyai, Y Hu, SHM Pang, S Grabow, A Strasser, SL Nutt, WS Alexander, GK Smyth, AK Voss, T Thomas

Blood | Published : 2015

Abstract

The histone acetyltransferase MOZ (MYST3, KAT6A) is the target of recurrent chromosomal translocations fusing the MOZ gene to CBP, p300, NCOA3, or TIF2 in particularly aggressive cases of acute myeloid leukemia. In this study, we report the role of wild-type MOZ in regulating B-cell progenitor proliferation and hematopoietic malignancy. In the Eν-Myc model of aggressive pre-B/B-cell lymphoma, the loss of just one allele of Moz increased the median survival of mice by 3.9-fold. MOZ was required to maintain the proliferative capacity of B-cell progenitors, even in the presence of c-MYCoverexpression, by directly maintaining the transcriptional activity of genes required for normal B-cell devel..

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Grants


Funding Acknowledgements

This study was funded by grants from the National Health and Medical Research Council (NHMRC) project (1030704, 1008699, and 1010851), the NHMRC program (1054618, 1016647, and 1016701), NHMRC research fellowships (1058892) (G.K.S.), (1058344) (W.S.A.), (1003435) (T.T.), (575512) (A.K.V.), and (1020363) (A.S.), Lady Tata Research Award (S.G.), Cancer Council Victoria postdoctoral fellowship (S.G.), Leukemia and Lymphoma Society (SCOR grant 7001-13) (A.S.), Australian Research Council future fellowship (S.L.N.), Independent Research Institutes Infrastructure Support Scheme from the Australian Government's NHMRC, the Australia Cancer Research Fund, and the Victorian State Government Operational Infrastructure Support.