CDK9 recruits HUWE1 to degrade RARα and offers therapeutic opportunities for cutaneous T-cell lymphoma.

ABSTRACT: Cutaneous T-cell lymphoma (CTCL) is a heterogeneous non-Hodgkin lymphoma originating in the skin and invading the systemic hematopoietic system. Current treatments, including chemotherapy and monoclonal antibodies yielded limited responses with high incidence of side effects, highlighting the need for targeted therapy. Screening with small inhibitors library, herein we identify cyclin dependent kinase 9 (CDK9) as a driver of CTCL growth. Single-cell RNA-seq analysis reveals a CDK9^high malignant T cell cluster with a unique actively proliferating feature. Inhibition, depletion or proteolysis targeting chimera (PROTAC)-mediated degradation of CDK9 significantly reduces CTCL cell growth in vitro and in murine models. CDK9 also promotes degradation of retinoic acid receptor α (RARα)

SUBMITTER: Luo CH 

PROVIDER: S-EPMC11618697 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature