Overall outcomes are dismal in patients with relapsed/refractory (R/R) acute myeloid leukemia (AML). Alvocidib is a multi-cyclin-dependent kinase (multi-CDK) inhibitor with potent activity against CDK9. CDK9 forms a complex with cyclin T1, positive transcription elongation factor b, which exists in a superenhancer complex to regulate the activity of RNA-polymerase II. By inhibiting CDK9, alvocidib leads to the suppression of RNA-polymerase II-mediated transcription of myeloid cell leukemia-1 (MCL-1), a pro-survival BCL-2 family member that inhibits the intrinsic pathway of apoptosis and promotes leukemia survival [ 1 ]. MCL-1 has a short half-life and is dependent on continuous transcription from RNA-polymerase II for activity [ 2 ]. There is a strong rationale to investigate targeted strategies of MCL-1 inhibition in diverse AML treatment settings.
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Zeidner et al. (2021) studied this question.
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