Journal article
JAK2 is dispensable for maintenance of JAK2 mutant B-cell acute lymphoblastic leukemias
SK Kim, DA Knight, LR Jones, S Vervoort, AP Ng, JF Seymour, JE Bradner, M Waibel, L Kats, RW Johnstone
Genes and Development | COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT | Published : 2018
Abstract
Activating JAK2 point mutations are implicated in the pathogenesis of myeloid and lymphoid malignancies, including high-risk B-cell acute lymphoblastic leukemia (B-ALL). In preclinical studies, treatment of JAK2 mutant leukemias with type I JAK2 inhibitors (e.g., Food and Drug Administration [FDA]-approved ruxolitinib) provided limited single-agent responses, possibly due to paradoxical JAK2Y1007/1008 hyperphosphorylation induced by these agents. To determine the importance of mutant JAK2 in B-ALL initiation and maintenance, we developed unique genetically engineered mouse models of B-ALL driven by overexpressed Crlf2 and mutant Jak2, recapitulating the genetic aberrations found in human B-A..
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Grants
Awarded by National Health and Medical Research Council
Funding Acknowledgements
We thank Novartis for generously supplying ruxolitinib and CHZ868; Dr. Johannes Zuber and Dr. Geoff Matthews for assistance with shRNA technology; Viki Milovac, Sophie Curcio, and Ralph Rossi for flow cytometry assistance; and Eva Vidacs, Lauren Dawes, and Kat Papastratos for animal husbandry. This work was supported by a project grant from the Cancer Council Victoria (to M.W. and R.W.J.), a Cancer Therapeutics Cooperative Research Centre PhD Top-Up Scholarship and Melbourne International Research Scholarship (to S.-K.K.), a C.J. Martin Fellowship from the National Health and Medical Research Council (NHMRC; to L.K.), NHMRC project grants (APP1122783 and APP 1060179 to A.P.N.), NHMRC Program grants (454569 to R.W.J., and 1113577 to A.P.N.), a NHMRC Senior Principal Research Fellowship (R.W.J.), and The Kids' Cancer Project (S.V. and R.W.J.).