MCL-1 Dependence
in Acute Myeloid Leukemia (AML)

Disease progression and treatment resistance in a subset* of AML have been associated with MCL-1. This is referred to as MCL-1 dependence.1

In MCL-1–dependent AML, MCL-1 inhibits apoptosis and sustains the survival of leukemic blasts, which may lead to relapse or resistance to treatment.1,2

The expression of MCL-1 in leukemic blasts is regulated by cyclin-dependent kinase 9 (CDK9).3,4 Because of the short half-life of MCL-1 (2-4 hours), the effects of targeting upstream pathways are expected to reduce MCL-1 levels rapidly.5 Inhibition of CDK9 has been shown to block MCL1 transcription, resulting in the rapid downregulation of MCL-1 protein, thus restoring the normal apoptotic regulation.1

Watch this video to learn more about the role of MCL-1 as an apoptosis inhibitor in MCL-1–dependent AML.

Learn more about our ongoing clinical trials in MCL-1–dependent AML.

References: 1. Thomas D, Powell JA, Vergez F, et al. Targeting acute myeloid leukemia by dual inhibition of PI3K signaling and Cdk9-mediated Mcl-1 transcription. Blood. 2013;122(5):738-748. 2. Glaser SP, Lee EF, Trounson E, et al. Anti-apoptotic Mcl-1 is essential for the development and sustained growth of acute myeloid leukemia. Genes Dev. 2012;26(2):120-125. 3. Chen R, Keating MJ, Gandhi V, Plunkett W. Transcription inhibition by flavopiridol: mechanism of chronic lymphocytic leukemia cell death. Blood. 2005;106(7):2513-2519. 4. Ocana A, Pandiella A. Targeting oncogenic vulnerabilities in triple negative breast cancer: biological bases and ongoing clinical studies. Oncotarget. 2017;8(13):22218-22234. 5. Gores GJ, Kaufmann SH. Selectively targeting Mcl-1 for the treatment of acute myelogenous leukemia and solid tumors. Genes Dev. 2012;26(4):305-311.

*The prevalence of MCL-1–dependent AML is under investigation.

Targeted therapy is at the heart of our pipeline.

Targeted therapy is at the heart of
our pipeline.

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See why we're investigating MCL‐1 dependent AML.

See why we’re investigating MCL-1
as a potential apoptosis inhibitor.

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Learn about our clinical trials currently underway.

Learn about our clinical trials
currently underway.

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