Journal article

Cotargeting BCL-2 and MCL-1 in high-risk B-ALL

Donia M Moujalled, Diane T Hanna, Soroor Hediyeh-zadeh, Giovanna Pomilio, Lauren Brown, Veronique Litalien, Ray Bartolo, Shaun Fleming, Maia Chanrion, Sebastien Banquet, Ana-Leticia Maragno, Laurence Kraus-Berthier, Marie Schoumacher, Charles G Mullighan, Angela Georgiou, Christine A White, Guillaume Lessene, David CS Huang, Andrew W Roberts, Olivier Geneste Show all

BLOOD ADVANCES | AMER SOC HEMATOLOGY | Published : 2020

Abstract

Improving survival outcomes in adult B-cell acute lymphoblastic leukemia (B-ALL) remains a clinical challenge. Relapsed disease has a poor prognosis despite the use of tyrosine kinase inhibitors (TKIs) for Philadelphia chromosome positive (Ph+ ALL) cases and immunotherapeutic approaches, including blinatumomab and chimeric antigen receptor T cells. Targeting aberrant cell survival pathways with selective small molecule BH3-mimetic inhibitors of BCL-2 (venetoclax, S55746), BCL-XL (A1331852), or MCL1 (S63845) is an emerging therapeutic option. We report that combined targeting of BCL-2 and MCL1 is synergistic in B-ALL in vitro. The combination demonstrated greater efficacy than standard chemot..

View full abstract

Grants

Awarded by National Health and Medical Research Council


Awarded by Leukemia and Lymphoma Society (Specialized Center of Research) grant


Funding Acknowledgements

This work was supported by the National Health and Medical Research Council program grant GNT1113577 (A.W.R.), project grants GNT1060179 and GNT1122783 (A.P.N.), Cancer Council Victoria, Victorian Cancer Agency, Leukaemia Foundation of Australia, Leukemia and Lymphoma Society (Specialized Center of Research) grant 20454683, Australian Cancer Research Foundation, Monash Partners, the Alfred Foundation, and the Medical Research Future Fund, Children's Cancer Foundation, The Department of Health and Human Services through the Victorian Cancer Agency (S.L.K.), as well as by philanthropic support from the Walter and Eliza Hall Institute, and operational infrastructure grants through the Australian Government Independent Research Institute Infrastructure Support Scheme and the Victorian Government Operational Infrastructure Support. This work has received funding support from Servier.