Blockade of crizotinib-induced BCL2 elevation in ALK-positive anaplastic large cell lymphoma triggers autophagy associated with cell death.

ABSTRACT: Anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphomas are tumors that carry translocations involving the ALK gene at the 2p23 locus, leading to the expression of ALK tyrosine kinase fusion oncoproteins. Amongst hematologic malignancies, these lymphomas are particular in that they express very low levels of B-cell lymphoma 2 (BCL2), a recognized inhibitor of apoptosis and autophagy, two processes that share complex interconnections. We have previously shown that treatment of ALK-positive anaplastic large cell lymphoma cells with the ALK tyrosine kinase inhibitor crizotinib induces autophagy as a pro-survival response. Here, we observed that crizotinib-mediated inactivation of ALK caused an increase in BCL2 levels that restrained the cytotoxic effects of the drug.

SUBMITTER: Torossian A 

PROVIDER: S-EPMC6601090 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature