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  • Monograph from the Acute Leukemia Forum 1999 on Advances and Controversies in the Therapy of Acute Myelogenous Leukemia
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New agents for acute myelogenous leukemia

Abstract

New agents for the treatment of acute myelogenous leukemia are discussed that reflect different treatment mechanisms. These include histone acetylation, angiogenesis inhibition, protein kinase inhibitors, and a novel retinoid. Efficacy and safety in phase I and phase II trials reviewed, as well as the problems involved in crossing over from treatment of solid tumors to blood disorders.

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References

  1. Lin RJ, Nagy L, Inoue S, Shao W, Miller WH Jr, Evans RM . Role of the histone deacetylase complex in acute promyelocytic leukaemia Nature 1998 391: 811–814

    Article  CAS  PubMed  Google Scholar 

  2. Grignani F, De Matteis S, Nervi C, Tomassoni L, Gelmetti V, Cioce M, Fanelli M, Ruthardt M, Ferrara FF, Zamir I, Seiser C, Grignani F, Lazar MA, Minucci S, Pelicci PG . Fusion proteins of the retinoic acid receptor-alpha recruit histone deacetylase in promyelocytic leukaemia Nature 1998 391: 815–818

    Article  CAS  PubMed  Google Scholar 

  3. He LZ, Guidez F, Tribioli C et al. Distinct interactions of PML-RARalpha and PLZF-RARalpha with corepressors determine differential responses to RA in APL Nat Genet 1998 18: 126–135

    Article  CAS  PubMed  Google Scholar 

  4. David G, Alland L, Hong SH, Wong CW, DePinho RA, Dejean A . Histone deacetylase associated with mSin3A mediates repression by the acute promyelocytic leukemia-associated PLZF protein Oncogene 1998 16: 2549–2556

    Article  CAS  PubMed  Google Scholar 

  5. Guidez F, Ivins S, Zhu J, Soderstrom M, Waxman S, Zelent A . Reduced retinoic acid-sensitivities of nuclear receptor corepressor binding to PML- and PLZF-RARalpha underlie molecular pathogenesis and treatment of acute promyelocytic leukemia Blood 1998 91: 2634–2642

    CAS  PubMed  Google Scholar 

  6. Gelmetti V, Zhang J, Fanelli M, Minucci S, Pelicci PG, Lazar MA . Aberrant recruitment of the nuclear receptor corepressor–histone deacetylase complex by the acute myeloid leukemia fusion partner ETO Mol Cell Biol 1998 18: 7185–7191

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Lutterbach B, Westendorf JJ, Linggi B, Patten A, Moniwa M, Davie JR, Huynh KD, Bardwell VJ, Lavinsky RM, Rosenfeld MG, Glass C, Seto E, Hiebert SW . ETO, a target of t (8;21) in acute leukemia, interacts with the N-CoR and mSin3 corepressors Mol Cell Biol 1998 18: 7176–7184

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Collins SJ . Acute promyelocytic leukemia: relieving repression induces remission Blood 1998 91: 2631–2633

    CAS  PubMed  Google Scholar 

  9. Wang J, Hoshino T, Redner RL, Kajigaya S, Liu JM . ETO, fusion partner in t (8;21) acute myeloid leukemia, represses transcription by interaction with the human N-CoR/mSin3/HDAC1 complex Proc Natl Acad Sci USA 1998 95: 10860–10865

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Byrd JC, Shinn C, Ravi R, Willis CR, Waselenko JK, Flinn IW, Dawson NA, Grever MR . Depsipeptide (FR901228): a novel therapeutic agent with selective, in vitro activity against human B-cell chronic lymphocytic leukemia cells Blood 1999 94: 1401–1408

    CAS  PubMed  Google Scholar 

  11. Lea MA, Tulsyan N . Discordant effects of butyrate analogues on erythroleukemia cell proliferation, differentiation and histone deacetylase Anticancer Res 1995 15: 879–883

    CAS  PubMed  Google Scholar 

  12. Yu KH, Weng LJ, Fu S, Piantadosi S, Gore SD . Augmentation of phenylbutyrate-induced differentiation of myeloid leukemia cells using all-trans retinoic acid Leukemia 1999 13: 1258–1265

    Article  CAS  PubMed  Google Scholar 

  13. Nan X, Ng HH, Johnson CA, Laherty CD, Turner BM, Eisenman RN, Bird A . Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex Nature 1998 393: 386–389

    Article  CAS  PubMed  Google Scholar 

  14. Jones PL, Veenstra GJ, Wade PA, Vermaak D, Kass SU, Landsberger N, Strouboulis J, Wolffe AP . Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription Nat Genet 1998 19: 187–191

    Article  CAS  PubMed  Google Scholar 

  15. Cameron EE, Bachman KE, Myohanen S, Herman JG, Baylin SB . Synergy of demethylation and histone deacetylase inhibition in the re-expression of genes silenced in cancer Nat Genet 1999 21: 103–107

    Article  CAS  PubMed  Google Scholar 

  16. Folkman J . Tumor angiogenesis: therapeutic implications New Engl J Med 1971 285: 1182–1186

    Article  CAS  PubMed  Google Scholar 

  17. Nguyen M, Watanabe H, Budson AE, Richie JP, Hayes DF, Folkman J . Elevated levels of an angiogenic peptide, basic fibroblast growth factor, in the urine of patients with a wide spectrum of cancers J Natl Cancer Inst 1994 86: 356–361

    Article  CAS  PubMed  Google Scholar 

  18. Perez-Atayde AR, Sallan SE, Tedrow U, Connors S, Allred E, Folkman J . Spectrum of tumor angiogenesis in the bone marrow of children with acute lymphoblastic leukemia Am J Pathol 1997 150: 815–821

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Fiedler W, Graeven U, Ergun S, Verago S, Kilic N, Stockschlader M, Hossfeld DK . Vascular endothelial growth factor, a possible paracrine growth factor in human acute myeloid leukemia Blood 1997 89: 1870–1875

    CAS  PubMed  Google Scholar 

  20. Wang S, Vrana JA, Bartimole TM, Freemerman AJ, Jarvis WD, Kramer LB, Krystal G, Dent P, Grant S . Agents that down-regulate or inhibit protein kinase C circumvent resistance to 1-beta-D-arabinofuranosylcytosine-induced apoptosis in human leukemia cells that overexpress Bcl-2 Mol Pharmacol 1997 52: 1000–1009

    Article  CAS  PubMed  Google Scholar 

  21. Liu G, Wu M, Levi G, Ferrari N . Inhibition of cancer cell growth by all-trans retinoic acid and its analog N-(4-hydroxyphenyl) retinamide: a possible mechanism of action via regulation of retinoid receptors expression Int J Cancer 1998 78: 248–254

    Article  CAS  PubMed  Google Scholar 

  22. Reed JC . Fenretinide: the death of a tumor cell J Natl Cancer Inst 1999 91: 1099–1100

    Article  CAS  PubMed  Google Scholar 

  23. Sun SY, Yue P, Lotan R . Induction of apoptosis by N-(4-hydroxyphenyl) retinamide and its association with reactive oxygen species, nuclear retionic acid receptors, and apoptosis-related genes in human prostate carcinoma cells Mol Pharmacol 1999 55: 403–410

    CAS  PubMed  Google Scholar 

  24. Bagniewski PG, Reid JM, Villablanca JG, Reynolds CP, Ames MM . A phase I pharmacokinetic study of fenretinide in children with high-risk solid tumors AACR Proc 1999 40: 92

    Google Scholar 

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Zwiebel, J. New agents for acute myelogenous leukemia. Leukemia 14, 488–490 (2000). https://doi.org/10.1038/sj.leu.2401662

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  • DOI: https://doi.org/10.1038/sj.leu.2401662

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