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Original Article: Research

Flavopiridol induces BCL-2 expression and represses oncogenic transcription factors in leukemic blasts from adults with refractory acute myeloid leukemia

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Pages 1999-2006 | Received 22 Apr 2011, Accepted 17 May 2011, Published online: 05 Jul 2011

References

  • Karp JE, Smith MA. The molecular pathogenesis of treatment-induced (secondary) leukemias: foundations for treatment and prevention. Semin Oncol 1997;24:103–113.
  • Lowenberg B, Downing RJ, Burnett A. Acute myeloid leukemia. N Engl J Med 1999;341:1051–1062.
  • Tallman MS, Gilliland DG, Rowe JM. Drug therapy for acute myeloid leukemia. Blood 2005;106:1154–1163.
  • Rollison DE, Howlader N, Smith MT, et al. Epidemiology of myelodysplastic syndromes and chronic myeloproliferative disorders in the United States, 2001-2004, using data from the NAACCR and SEER programs. Blood 2008;112:45–52.
  • Fathi AT, Karp JE. New agents in AML: beyond cytarabine and anthracyclines. Curr Oncol Rep 2009;11:346–352.
  • Naik RG, Kattige SL, Bhat SV, Alreja B, de Souza NJ, Rupp RH. An anti-inflammatory cum immunomodulatory piperidinylbenzopyranone from Dysoxylum binectariferum: isolation, structure, and total synthesis. Tetrahedron 1998;44:2081–2086.
  • Melillo G, Sausville EA, Cloud K, Lahusen T, Varesio L, Senderowicz AM. Flavopiridol, a protein kinase inhibitor, down-regulates hypoxic induction of vascular endothelial growth factor expression in human monocytes. Cancer Res 1999;59:5433–5437.
  • Senderowicz AM, Sausville EA. Preclinical and clinical development of cyclin-dependent kinase modulators. J Natl Cancer Inst 2000;92:376–387.
  • Chao S-H, Price D-H. Flavopiridol inactivates p-TEFb and blocks most RNA polymerase II transcription in vivo. J Biol Chem 2001;76:31793–31799.
  • Klasa RJ, List AF, Cheson BD. Rational approaches to design of therapeutics targeting molecular markers. Hematology 2001;1:443–462.
  • Karp JE, Ross DD, Yang W, et al. Timed sequential therapy of acute leukemia with flavopiridol: in vitro model for a phase I clinical trial. Clin Cancer Res 2003;9:307–315.
  • Sausville EA. Complexities in the development of cyclin-dependent kinase inhibitor drugs. Trends Mol Med 2002;8:S32–S37.
  • Shapiro GI. Cyclin-dependent kinase pathways as targets for cancer treatment. J Clin Oncol 2006;24:1770–1783.
  • Sedlacek HH. Mechanisms of action of flavopiridol. Crit Rev Oncol Hematol 2001;38:139–170.
  • Lee YK, Isham CR, Kaufman SH, Bible KC. Flavopiridol disrupts STAT3/DNA interactions, attenuates STAT3-directed transcription, and combines with the Jak kinase inhibitor AG490 to achieve cytotoxic synergy. Mol Cancer Ther 2006;5:138–148.
  • Kitada S, Zapata JM, Andreeff M, Reed JC. Protein kinase inhibitors flavopiridol and 7-hydroxy-staurosporine down-regulate anti apoptosis proteins in B-cell chronic lymphocytic leukemia. Blood 2000;96:393–397.
  • Gojo I, Zhang B, Fenton RG. The cyclin-dependent kinase inhibitor flavopiridol induces apoptosis in multiple myeloma cells through transcriptional repression and down-regulation of Mcl-1. Clin Cancer Res 2002;8:3527–3538.
  • König A, Schwartz GK, Mohammad RM, Al-Katib A, Gabrilove JL. The novel cyclin-dependent kinase inhibitor flavopiridol downregulates Bcl-2 and induces growth arrest and apoptosis in chronic B cell leukemia lines. Blood 1997;90:4307–4312.
  • Schuringa JJ, Wierenga AT, Kruijer W, Vellenga E. Constitutive Stat3, Tyr705, and Ser727 phosphorylation in acute myeloid leukemia cells caused by the autocrine secretion of interleukin-6. Blood 2000;95:3765–70.
  • Hillion J, Dhara S, Sumter TF, et al. The HMGA1a-STAT3 axis: an ‘Achilles heel’ for acute leukemia? Cancer Res 2008;68:10121–10127.
  • Benekli M, Baumann H, Wetzler M. Targeting signal transducer and activator of transcription signaling pathway in leukemias. J Clin Oncol 2009;27:4422–4432.
  • Karp JE, Passaniti A, Gojo I, et al. Phase I and pharmacokinetic study of flavopiridol followed by 1-B-D arabinofuranosylcytosine and mitoxantrone in relapsed and refractory acute leukemias. Clin Cancer Res 2005;11:8403–8412.
  • Karp JE, Smith BD, Levis MJ, et al. Sequential flavopiridol, cytosine arabinoside, and mitoxantrone: a phase II trial in adults with poor-risk acute myelogenous leukemia. Clin Cancer Res 2007;13:4467–4473.
  • Wood LJ, Mukherjee M, Dolde CE, et al. HMG-I/Y: a new c-Myc target gene and potential human oncogene. Mol Cell Biol 2000;20:5490–5502.
  • Wood LJ, Maher J, Bunton TE, Resar LMS. The oncogenic properties of the HMG-I gene family. Cancer Res 2000;60:4256–4261.
  • Pedulla ML, Treff NR, Resar LMS, Reeves R. Cloning and comparative sequence analysis of the murine Hmgiy (Hmga1) gene. Gene 2001;271:51–58.
  • Dolde CE, Mukherjee M, Cho C, Resar LM. The role of HMG-A1/Y in the human breast cancer. Breast Cancer Res Treat 2002;71:181–191.
  • Pomeroy SL, Tamayo P, Gaasenbeek M, et al. Prediction of central nervous system embryonal tumour outcome based on gene expression. Nature 2002;415:436–442.
  • Pierantoni GM, Agosti V, Fedele M, et al. High-mobility group A1 proteins are overexpressed in human leukemias. Biochem J 2003;372:145–150.
  • Takaha N, Resar LM, Vindivich D, Coffey DS. High mobility protein HMGI(Y) enhances tumor cell growth, invasion, and matrix metalloproteinase-2 expression in prostate cancer cells. Prostate 2004;60:160–167.
  • Dhar A, Hu J, Reeves R, Resar L, Colburn N. Dominant negative c-Jun (TAM67) target genes: HMGA1 is required for tumor promoter-induced transformation. Oncogene 2004;23:4466–4476.
  • Hommura F, Katabami M, Leaner VD, et al. HMG-I/Y is a cJun/AP-1 responsive gene and is necessary for cJun induced anchorage-independent growth. Mol Cancer Res 2004;2:303–314.
  • Xu Y, Sumter TF, Bhattacharya R, et al. HMG-I transgenic mice develop highly penetrant aggressive lymphoid malignancy in transgenic mice and is overexpressed in human leukemia. Cancer Res 2004;64:3371–3375.
  • Fedele M, Pentimalli F, Baldassarre G, et al. Transgenic mice overexpressing the wild-type form of the HMGA1 gene develop mixed growth hormone/prolactin cell pituitary adenomas and natural killer cell lymphomas. Oncogene 2005;24:3427–3435.
  • Tesfaye A, Di Cello F, Hillion J, et al. The high-mobility group A1 gene up-regulates cyclooxygenase 2 expression in uterine tumorigenesis. Cancer Res 2007;67:3998–4004.
  • Ben-Porath I, Thomson MW, Carey VJ, et al. An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors. Nat Genet 2008;40:499–507.
  • Di Cello F, Hillion J, Aderinto A, et al. COX-2 inhibitors block uterine tumorigenesis in HMGA1a transgenic mice and human uterine cancer xenografts. Mol Cancer Ther 2008;7:2090–2095.
  • Hillion J, Wood LJ, Mukherjee M, et al. Upregulation of MMP-2 by HMGA1 promotes transformation in undifferentiated, large-cell lung cancer. Mol Cancer Res 2009;7:1803–1812.
  • Hristov AC, Cope L, Di Cello F, et al. HMGA1 correlates with advanced tumor grade and decreased survival in pancreatic ductal adenocarcinoma. Mod Pathol 2010;23:98–104.
  • Resar LMS. The High Mobility Group A1 gene: transforming inflammatory signals into cancer? Cancer Res 2010;70:436–439.
  • Karp JE, Smith BD, Resar LS, et al. Phase I and pharmacokinetic study of bolus-infusion flavopiridol followed by cytosine arabinoside and mitoxantrone for acute leukemias. Blood 2011;117:3302–3310.
  • Di Cello F, Hillion J, Hristov A, et al. HMGA2 participates in neoplastic transformation in human lung cancer. Mol Cancer Res 2008;6:743–750.
  • Hristov A, Delos Reyes M, Singh M, et al. HMGA2 protein expression correlates with lymph node metastasis and increased tumor grade in pancreatic ductal adenocarcinoma. Mod Pathol 2009;22:43–49.
  • Ikeda K, Mason PJ, Bessler M: 3′UTR truncated HmgA2 cDNA causes MPN-like hematopoiesis by conferring a clonal growth advantage at the level of HSC in mice. Blood 2011 Apr 1. [Epub ahead of print]
  • Resar L, Brodsky R. ΔHMGA2: ‘Let’ing go with clonal expansion? Blood 2011;117:5788–5790.
  • Zhou G, Chen J, Lee S, Clark T, Rowley JD, Wang SM. The pattern of gene expression in human CD34+ stem/progenitor cells. Proc Natl Acad Sci USA 2001;98:13966–13971.
  • Chou B-K, Mali P, Huang X, et al. Efficient human iPS cell derivation by a non-integrating plasmid from blood cells with unique epigenetic and gene expression signantures. Cell Res 2011;21:518–529.
  • Somervaille TC, Matheny CJ, Spencer GJ, et al. Hierarchical maintenance of MLL myeloid leukemia stem cells employs a transcriptional program shared with embryonic rather than adult stem cells. Cell Stem Cell 2009;4:129–140.
  • Byrd JC, Lin TS, Dalton JT, et al. Flavopiridol administered using a pharmacologically derived schedule is associated with marked clinical efficacy in refractory, genetically high-risk chronic lymphocytic leukemia. Blood 2007;109:399–404.
  • Karp JE, Blackford A, Smith BD, et al. Clinical activity of sequential flavopiridol, cytosine arabinoside, and mitoxantrone for adults with newly diagnosed, poor-risk acute myelogenous leukemia. Leuk Res 2010;34:877–882.
  • Decker RH, Wang S, Dai Y, Dent P, Grant S. Loss of BCL-2 phosphorylation loop domain is required to protect human myeloid leukemic cells from flavopiridol-mediated damage and apoptosis. Cancer Biol Ther 2002;1:136–144.
  • Chung Y-J, Kim T-M, Eaves C, Oh I-H. Role of Stat3 for hematopoietic stem cells. Int J Hematol 2002;S1:152 [Abstract].
  • Pulikkan JA, Dengler V, Peramangalam PS, et al. Cell-cycle regulator E2F1 and microRNA-223 comprise an autoregulatory negative feedback loop in acute myeloid leukemia. Blood 2009;115:1768–1778.

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