BH3 mimetic drugs overcome the microenvironment-induced resistance to crizotinib in ALK+ anaplastic large cell lymphoma.

ABSTRACT:

Abstract

Resistance to first-line chemotherapies and crizotinib in anaplastic large cell lymphoma (ALCL) represents a significant challenge, often leading to a dismal outcome. Despite recent advancements, the dissection of the intrinsic and extrinsic molecular alterations underlying crizotinib resistance in ALCL is still poorly understood. Here, we transcriptionally unraveled the bidirectional interplay between anaplastic lymphoma kinase (ALK)-driven ALCL (ALK+ ALCL) and stromal cells in the presence of crizotinib at bulk and single-cell levels and identified that the microenvironment provides prosurvival signals leading to crizotinib persistence in ALK+ ALCL. We detected increased B-cell lymphoma 2 (BCL2) expression and downregulation of pathways related to apoptosis in crizotinib

SUBMITTER: Pignataro C 

PROVIDER: S-EPMC12494848 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature