Conference Proceedings
Identification of Potent BH3-Mimetic Combinations Targeting Pro-Survival Pathways in Human B-Cell Acute Lymphoblastic Leukemia
Donia M Moujalled, Diane T Hanna, Giovanna Pomilio, Veronique Litalien, Shaun Fleming, Marie Chanrion, Ana-Leticia Maragno, Laurence Kraus-Berthier, Seong Lin Khaw, Guillaume Lessene, David Huang, Andrew W Roberts, Olivier Geneste, Paul G Ekert, Ashley P Ng, Andrew H Wei
BLOOD | AMER SOC HEMATOLOGY | Published : 2018
Abstract
Abstract Background Precursor-B acute lymphoblastic leukemia (B-ALL) is an aggressive hematological malignancy. Relapsed disease has a poor prognosis, despite improved outcomes with tyrosine kinase inhibitors for Ph+ cases and immunotherapeutic approaches, such as blinotumomab and CAR-T cells. Targeting cell survival with novel small molecule BH3-mimetic inhibitors of BCL-2 (e.g. Souers et al Nat Med 2013, Roberts et al, NEJM 2016 and Casara et al, Oncotarget 2018), BCL-XL (Lessene et al, Nat Chem Biol, 2013) or MCL1 (Kotschy et al, Nature 2016) is an emerging therapeutic option. BCL-2 is reported to have a pro-survival role in BCR-ABL1, JAK2 fus..
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