Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2018 Feb 23;37(1):36.
doi: 10.1186/s13046-018-0704-8.

CDK9 inhibitors in acute myeloid leukemia

Silvia Boffo  1 , Angela Damato  1   2 , Luigi Alfano  3 , Antonio Giordano  4   5
Affiliations
Review

CDK9 inhibitors in acute myeloid leukemia

Silvia Boffo et al. J Exp Clin Cancer Res. .

Abstract

Current treatment for acute myeloid leukemia (AML) is less than optimal, but increased understanding of disease pathobiology and genomics has led to clinical investigation of novel targeted therapies and rational combinations. Targeting the cyclin-dependent kinase 9 (CDK9) pathway, which is dysregulated in AML, is an attractive approach. Inhibition of CDK9 leads to downregulation of cell survival genes regulated by super enhancers such as MCL-1, MYC, and cyclin D1. As CDK9 inhibitors are nonselective, predictive biomarkers that may help identify patients most likely to respond to CDK9 inhibitors are now being utilized, with the goal of improving efficacy and safety.

Keywords: Acute myeloid leukemia; CDK9 inhibitor; MCL-1; MYC; P-TEFb; Positive transcription elongation factor b.

PubMed Disclaimer

Conflict of interest statement

Ethics approval and consent to participate

Not applicable

Consent for publication

Not applicable

Competing interests

The authors declare they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Role of cyclin-dependent kinase (CDK)9 in gene transcription and cancer cell survival. CDK9 associates with cyclin T1 (CycT), forming the positive transcription elongation factor b (P-TEFb) complex that regulates gene transcription elongation and mRNA maturation [15]. The P-TEFb complex remains inactive when bound to hexamethylene bisacetamide-inducible protein 1 (HEXIM1), which is associated with the noncoding 7SK small nuclear RNA (snRNA) [45]. Bromodomain protein 4 (BRD4) recruits P-TEFb to activate the complex and transcription. CDK9 phosphorylates the carboxyl terminal domain of RNA polymerase II (RNA Pol II), allowing transcriptional elongation and expression of genes such as MYC and MCL-1, which together increase proliferation and survival of cancer cells
See this image and copyright information in PMC

References

    1. SEER Cancer Stat Facts. Acute myeloid leukemia. Bethesda, MD: National Cancer Institute. https://seer.cancer.gov/statfacts/html/amyl.html. Accessed 11 Aug 2017.
    1. Kumar CC. Genetic abnormalities and challenges in the treatment of acute myeloid leukemia. Genes Cancer. 2011;2:95–107. doi: 10.1177/1947601911408076. - DOI - PMC - PubMed
    1. Larson RA. Etiology and Management of therapy-related myeloid leukemia. Hematology Am Soc Hematol Educ Program. 2007:453–9. - PubMed
    1. O'Donnell MR, Tallman MS, Abboud CN, Altman JK, Appelbaum FR, Arber DA, Bhatt V, Bixby D, Blum W, Coutre SE, De Lima M, Fathi AT, Fiorella M, Foran JM, Gore SD, Hall AC, Kropf P, Lancet J, Maness LJ, Marcucci G, Martin MG, Moore JO, Olin R, Peker D, Pollyea DA, Pratz K, Ravandi F, Shami PJ, Stone RM, Strickland SA, Wang ES, Wieduwilt M, Gregory K, Ogba N. Acute Myeloid Leukemia, Version 3.2017, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2017;15(7):926–57. - PubMed
    1. Thein MS, Bershler WB, Jemal A, Yates JW, Baer MR. Outcome Of older patients with acute myeloid leukemia: an analysis of SEER data over three decades. Cancer. 2013;119:2720–2727. doi: 10.1002/cncr.28129. - DOI - PMC - PubMed

MeSH terms