Conference Proceedings

Acquired Mutations in BAX Confer Resistance to BH3 Mimetics in Acute Myeloid Leukemia

Donia M Moujalled, Fiona C Brown, Giovanna Pomilio, Natasha S Anstee, Veronique Litalien, Ella R Thompson, Thomas Morley, Sarah MacRaild, Chong C Chua, SeBastien Banquet, Maia Chanrion, Ana-Leticia Maragno, Marie Schoumacher, Marco J Herold, Guillaume Lessene, Olivier Geneste, David CS Huang, Andrew W Roberts, Piers Blombery, Andrew Wei

Blood | AMER SOC HEMATOLOGY | Published : 2020

Abstract

Background: Recent randomized trials have demonstrated improvements in overall survival (OS) for the BCL-2 inhibitor venetoclax (VEN) in combination with azacitidine and low dose cytarabine in older unfit patients with AML. Pre-clinical studies identified BAX deficiency as a potential mechanism of VEN resistance in AML, but this has not been observed in patients to date (Chen, Cancer Disc 2019). Methods: Patient samples were derived from studies approved by the Alfred Ethics Committee. BAX sequencing was performed using targeted sequencing. In vivo studies used NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice. S63845 and S55746 were obtained from Servi..

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