CDK7 inhibition induces apoptosis in acute myeloid leukemia cells and exerts synergistic antileukemic effects with azacitidine in vitro and in vivo

References

• Dohner H, Weisdorf DJ, Bloomfield CD. Acute Myeloid leukemia. N Engl J Med. 2015;373(12):1136–1152.
   PubMed Web of Science ®Google Scholar
• Shallis RM, Wang R, Davidoff A, et al. Epidemiology of acute myeloid leukemia: recent progress and enduring challenges. Blood Rev. 2019;36:70–87.
   PubMed Web of Science ®Google Scholar
• National Cancer Institute Surveillance, Epidemiology, and End Results Program. SEER*Explorer. 2019; [cited 2019 Oct 2]. Available from: https://seer.cancer.gov/explorer/.
   Google Scholar
• Pollyea DA, Bixby D, Perl A, et al. NCCN guidelines insights: acute myeloid leukemia, version 2.2021. J Natl Compr Canc Netw. 2021;19(1):16–27.
   PubMed Web of Science ®Google Scholar
• Dohner H, Estey E, Grimwade D, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017;129(4):424–447.
   PubMed Web of Science ®Google Scholar
• Kantarjian HM, Thomas XG, Dmoszynska A, et al. Multicenter, randomized, open-label, phase III trial of decitabine versus patient choice, with physician advice, of either supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia. J Clin Oncol. 2012;30(21):2670–2677.
   PubMed Web of Science ®Google Scholar
• Dombret H, Seymour JF, Butrym A, et al. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood. 2015;126(3):291–299.
   PubMed Web of Science ®Google Scholar
• Itzykson R, Thepot S, Berthon C, et al. Azacitidine for the treatment of relapsed and refractory AML in older patients. Leuk Res. 2015;39(2):124–130.
   PubMed Web of Science ®Google Scholar
• DiNardo CD, Pratz K, Pullarkat V, et al. Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood. 2019;133(1):7–17.
   PubMed Web of Science ®Google Scholar
• Carter JL, Hege K, Yang J, et al. Targeting multiple signaling pathways: the new approach to acute myeloid leukemia therapy. Signal Transduct Target Ther. 2020;5(1):288.
   PubMed Web of Science ®Google Scholar
• Whittaker SR, Mallinger A, Workman P, et al. Inhibitors of cyclin-dependent kinases as cancer therapeutics. Pharmacol Ther. 2017;173:83–105.
   PubMed Web of Science ®Google Scholar
• Sherr CJ, Roberts JM. CDK inhibitors: positive and negative regulators of G1-phase progression. Genes Dev. 1999;13(12):1501–1512.
   PubMed Web of Science ®Google Scholar
• Larochelle S, Merrick KA, Terret ME, et al. Requirements for Cdk7 in the assembly of Cdk1/cyclin B and activation of Cdk2 revealed by chemical genetics in human cells. Mol Cell. 2007;25(6):839–850.
   PubMed Web of Science ®Google Scholar
• Heidemann M, Hintermair C, Voß K, et al. Dynamic phosphorylation patterns of RNA polymerase II CTD during transcription. Biochim Biophys Acta. 2013;1829(1):55–62.
   PubMed Web of Science ®Google Scholar
• Morales F, Giordano A. Overview of CDK9 as a target in cancer research. Cell Cycle. 2016;15(4):519–527.
   PubMed Web of Science ®Google Scholar
• Chipumuro E, Marco E, Christensen CL, et al. CDK7 inhibition suppresses super-enhancer-linked oncogenic transcription in MYCN-driven cancer. Cell. 2014;159(5):1126–1139.
   PubMed Web of Science ®Google Scholar
• Aleem E, Arceci RJ. Targeting cell cycle regulators in hematologic malignancies. Front Cell Dev Biol. 2015;3:16.
   PubMed Web of Science ®Google Scholar
• Otto T, Sicinski P. Cell cycle proteins as promising targets in cancer therapy. Nat Rev Cancer. 2017;17(2):93–115.
   PubMed Web of Science ®Google Scholar
• Wang J, Zhang R, Lin Z, et al. CDK7 inhibitor THZ1 enhances antiPD-1 therapy efficacy via the p38alpha/MYC/PD-L1 signaling in non-small cell lung cancer. J Hematol Oncol. 2020;13(1):99.
   PubMed Web of Science ®Google Scholar
• Christensen CL, Kwiatkowski N, Abraham BJ, et al. Targeting transcriptional addictions in small cell lung cancer with a covalent CDK7 inhibitor. Cancer Cell. 2014;26(6):909–922.
   PubMed Web of Science ®Google Scholar
• Abudureheman T, Xia J, Li MH, et al. CDK7 inhibitor THZ1 induces the cell apoptosis of B-Cell acute lymphocytic leukemia by perturbing cellular metabolism. Front Oncol. 2021;11:663360.
   PubMed Web of Science ®Google Scholar
• Kwiatkowski N, Zhang T, Rahl PB, et al. Targeting transcription regulation in cancer with a covalent CDK7 inhibitor. Nature. 2014;511(7511):616–620.
   PubMed Web of Science ®Google Scholar
• Sampathi S, Acharya P, Zhao Y, et al. The CDK7 inhibitor THZ1 alters RNA polymerase dynamics at the 5’ and 3’ ends of genes. Nucleic Acids Res. 2019;47(8):3921–3936.
   PubMed Web of Science ®Google Scholar
• Chou TC. Drug combination studies and their synergy quantification using the Chou-Talalay method. Cancer Res. 2010;70(2):440–446.
   PubMed Web of Science ®Google Scholar
• Wertz IE, Kusam S, Lam C, et al. Sensitivity to antitubulin chemotherapeutics is regulated by MCL1 and FBW7. Nature. 2011;471(7336):110–114.
   PubMed Web of Science ®Google Scholar
• Kuo KL, Lin WC, Liu SH, et al. THZ1, a covalent CDK7 inhibitor, enhances gemcitabine-induced cytotoxicity via suppression of Bcl-2 in urothelial carcinoma. Am J Cancer Res. 2021;11(1):171–180.
   PubMed Web of Science ®Google Scholar
• Huang T, Ding X, Xu G, et al. CDK7 inhibitor THZ1 inhibits MCL1 synthesis and drives cholangiocarcinoma apoptosis in combination with BCL2/BCL-XL inhibitor ABT-263. Cell Death Dis. 2019;10(8):602.
   PubMedGoogle Scholar
• Compe E, Egly JM. TFIIH: When transcription met DNA repair. Nat Rev Mol Cell Biol. 2012;13(6):343–354.
   PubMed Web of Science ®Google Scholar
• Chow PM, Chang YW, Kuo KL, et al. CDK7 inhibition by THZ1 suppresses cancer stemness in both chemonaive and chemoresistant urothelial carcinoma via the hedgehog signaling pathway. Cancer Lett. 2021;507:70–79.
   PubMed Web of Science ®Google Scholar
• Campos L, Rouault JP, Sabido O, et al. High expression of bcl-2 protein in acute myeloid leukemia cells is associated with poor response to chemotherapy. Blood. 1993;81(11):3091–3096.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Kaufmann SH, Karp JE, Svingen PA, et al. Elevated expression of the apoptotic regulator Mcl-1 at the time of leukemic relapse. Blood. 1998;91(3):991–1000.
   PubMed Web of Science ®Google Scholar
• Bogenberger JM, Kornblau SM, Pierceall WE, et al. BCL-2 family proteins as 5-Azacytidine-sensitizing targets and determinants of response in myeloid malignancies. Leukemia. 2014;28(8):1657–1665.
   PubMed Web of Science ®Google Scholar
• De Blasio A, Vento R, Di Fiore R. Mcl-1 targeting could be an intriguing perspective to cure cancer. J Cell Physiol. 2018;233(11):8482–8498.
   PubMed Web of Science ®Google Scholar
• Dang CV. c-Myc target genes involved in cell growth, apoptosis, and metabolism. Mol Cell Biol. 1999;19(1):1–11.
   PubMed Web of Science ®Google Scholar
• Luo H, Li Q, O’Neal J, et al. c-Myc rapidly induces acute myeloid leukemia in mice without evidence of lymphoma-associated antiapoptotic mutations. Blood. 2005;106(7):2452–2461.
   PubMed Web of Science ®Google Scholar
• Zeng M, Kwiatkowski NP, Zhang T, et al. Targeting MYC dependency in ovarian cancer through inhibition of CDK7 and CDK12/13. Elife. 2018;7:e39030.
   Web of Science ®Google Scholar
• Lord CJ, Ashworth A. The DNA damage response and cancer therapy. Nature. 2012;481(7381):287–294.
   PubMed Web of Science ®Google Scholar