Journal article
Functional-genetic dissection of HDAC dependencies in mouse lymphoid and myeloid malignancies
GM Matthews, P Mehdipour, LA Cluse, KJ Falkenberg, E Wang, M Roth, F Santoro, E Vidacs, K Stanley, CM House, JR Rusche, CR Vakoc, J Zuber, S Minucci, RW Johnstone
Blood | Published : 2015
Abstract
Histone deacetylase (HDAC) inhibitors (HDACis) have demonstrated activity in hematological and solid malignancies. Vorinostat, romidepsin, belinostat, and panobinostat are Food and Drug Administration-approved for hematological malignancies and inhibit class II and/or class I HDACs, including HDAC1, 2, 3, and 6. We combined genetic and pharmacological approaches to investigate whether suppression of individual or multiple Hdacs phenocopied broad-acting HDACis in 3 genetically distinct leukemias and lymphomas. Individual Hdacs were depleted in murine acute myeloid leukemias (MLL-AF9;NrasG12D; PML-RARα acute promyelocytic leukemia [APL] cells) and Eμ-Myc lymphoma in vitro and in vivo. Striking..
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Awarded by National Institutes of Health
Funding Acknowledgements
This work was supported by a National Health and Medical Research Council (NHMRC) Biomedical Fellowship and a Peter MacCallum Cancer Foundation Grant (G.M.M.); a Fondazione Italiana per la ricerca sul cancro (FIRC) fellowship (P.M.); National Institutes of Health (grant CA 174793), Burroughs-Wellcome Fund Career Award for Medical Scientists, and Alex's Lemonade Stand Foundation "A" Award (C.R.V.); and NHMRC Program and Project Grants (Senior Principal Research Fellow), Cancer Council Victoria, Leukemia Foundation of Australia, Victorian Cancer Agency, and Australian Rotary Health Foundation (R.W.J.). Laboratory research is funded by an ERC Starting Grant (36860), Special Research Program of the Austrian Science Fund (grant F4710), and Boehringer Ingelheim (J.Z.); the Italian Association for Cancer Research, FIRC, National Research Council Flagship Project Epigen, and European Community (4D Cell Fate Project 277899) (S.M.).