Journal article

Venetoclax responses of pediatric ALL xenografts reveal sensitivity of MLL-rearranged leukemia

Seong Lin Khaw, Santi Suryani, Kathryn Evans, Jennifer Richmond, Alissa Robbins, Raushan T Kurmasheva, Catherine A Billups, Stephen W Erickson, Yuelong Guo, Peter J Houghton, Malcolm A Smith, Hernan Carol, Andrew W Roberts, David CS Huang, Richard B Lock

BLOOD | AMER SOC HEMATOLOGY | Published : 2016

Abstract

The clinical success of the BCL-2-selective BH3-mimetic venetoclax in patients with poor prognosis chronic lymphocytic leukemia (CLL) highlights the potential of targeting the BCL-2-regulated apoptotic pathway in previously untreatable lymphoid malignancies. By selectively inhibiting BCL-2, venetoclax circumvents the dose-limiting, BCL-XL-mediated thrombocytopenia of its less selective predecessor navitoclax, while enhancing efficacy in CLL. We have previously reported the potent sensitivity of many high-risk childhood acute lymphoblastic leukemia (ALL) xenografts to navitoclax. Given the superior tolerability of venetoclax, here we have investigated its efficacy in childhood ALL. We demonst..

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Grants

Awarded by National Institutes of Health, National Cancer Institute


Awarded by Leukemia and Lymphoma Society


Awarded by National Health and Medical Research Council (NHMRC) of Australia


Awarded by NHMRC


Awarded by NATIONAL CANCER INSTITUTE


Funding Acknowledgements

This research was funded by grants from the National Institutes of Health, National Cancer Institute (NOI-CM-42216 and NOI-CM-91001-03), the Leukemia and Lymphoma Society (SCOR 7417-07 and 7001-13), and the National Health and Medical Research Council (NHMRC) of Australia (1016647 and 1016701). S.S. was supported by Postdoctoral Fellowships from the Leukaemia Foundation of Australia and the Cure Cancer Australia Foundation, and an Early Career Fellowship from the Cancer Institute New South Wales. R.B.L., A.W.R., and D.C.S.H. are supported by Fellowships from the NHMRC (1059804, 1079560, 1043149). The authors thank AbbVie for providing navitoclax, venetoclax, A-1113567, and A-1155463. The Walter and Eliza Hall Institute of Medical Research is supported by an Independent Research Institutes Infrastructure Support Scheme grant 9000220 (NHMRC) and Victorian State Government Operational Infrastructure Support grant.