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CDK4/6 Inhibitor, Palbociclib, overcomes Venetoclax resistance mechanisms and outperforms single agents in Acute Myeloid Leukemia [RNA-Seq]

GSE291339 Homo sapiens Expression profiling by high throughput sequencing 6 samples Submitted 2025/11/11 Platform GPL24676
Summary
Venetoclax (ven) combined with the hypomethylating agent azacytidine (aza) is a widely used therapy for Acute Myeloid Leukemia (AML), however, most patients develop resistance. Using RNASeq, we identified loss of Ikaros (IKZF1) as a potential resistance mechanism to ven+palbo. Examination of cells with IKZF1-loss revealed upregulation of the receptor, AXL, with concordant AXL inhibitor sensitivity in AML tumors harboring IKZF1 mutations. This work suggests that the combination of ven+palbo is a potential novel therapy for AML for potential subpopulations that may benefit the most from this treatment, as well as targeting translation as a means to overcome ven resistance.
Published in
CDK4/6 inhibition overcomes venetoclax resistance mechanisms with enhanced combination activity in acute myeloid leukemia
Stewart ML, Gibbs J, Watanabe-Smith K et al. · Cell reports. Medicine 2026 · PMID 41468895 · doi:10.1016/j.xcrm.2025.102526
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Also filed as BioProject PRJNA1232939 and SRA study SRP568582. Searching any of these in the dataset finder brings you back here.

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