Advances in acute myeloid leukemia (AML) genomics and targeted therapies include the recently approved BCL2 inhibitor venetoclax. The association between BCL2 expression and patient outcome was analyzed in a series of 176 consecutive AML patients at diagnosis (Dx), post-induction (PI), complete remission (CR) and relapse (RL). Levels increased significantly at relapse (mean 1.07 PI/0.96 CR vs. 2.17 RL, p = 0.05/p = 0.03). In multivariate analysis, high BCL2-Dx were marginally associated with worse progression-free survival, while high PI levels or at CR had an independent negative impact on outcome (PI: HR 1.58, p = 0.014; CR: HR 1.96, p = 0.008). This behavior of high PI or CR BCL2 levels and increased risk was maintained in a homogeneous patient subgroup of age <70 and intermediate cytogenetic risk (PI: HR 2.44, p = 0.037; CR: HR 2.71, p = 0.049). Finally, for this subgroup, high BCL2 at relapse indicated worse overall survival (OS, HR 1.15, p = 0.05). In conclusion, high BCL2 levels PI or at CR had an independent negative impact on patient outcome. Therefore, BCL2 expression is a dynamic marker that may be useful during AML patient follow up, and BCL2 levels at PI and/or CR may influence response to anti-BCL2 therapy.
Keywords: BCL2 inhibitors; acute myeloid leukemia; biomarkers; induction therapy; molecular diagnostics; patient outcome.