Integrative Transcriptomic and Functional Analysis of PKMYT1 Reveals a Potential Therapeutic Target in Chronic Lymphocytic Leukemia

Chronic lymphocytic leukemia (CLL) is a clinically and molecularly heterogeneous disease. PKMYT1, a G2/M cell cycle kinase, has been implicated in tumor progression in several cancers, but its role in CLL remains unclear. We evaluated PKMYT1 expression in primary CLL samples and analyzed associations with cytogenetic features and clinical parameters. PKMYT1 expression was heterogeneous and correlated with adverse features, including complex karyotype and elevated leukocyte counts. Comparative transcriptomic analyses between high- and low-expression groups revealed enrichment of pathways related to chromatin remodeling, DNA repair, and mitotic regulation. In MEC1 cells, pharmacological PKMYT1 inhibition significantly reduced Cancer cell viability. PCR analysis showed upregulation of TP53, CASP3, Bak, GSDMD, BCL2, CASP1, IL1β, RIPK1, and RIPK3, indicating activation of apoptotic, inflammasome-associated, and necroptotic pathways. Collectively, these findings demonstrate that PKMYT1 is heterogeneously expressed in CLL, associated with adverse cytogenetic and clinical features, and critical for cell survival, highlighting its potential as a therapeutic target.