New Developmental Agents and Directions in the Treatment of Acute Myelogenous Leukemia

  • B. D. Cheson
Conference paper
Part of the Haematology and Blood Transfusion Hämatologie und Bluttransfusion book series (HAEMATOLOGY, volume 41)

Abstract

The prognosis for patients with acute myelogenous leukemia (AML) has not improved substantially in more than a decade. Regimens based on an anthracycline (e.g. daunorubicin) and cytarabine, induce complete remissions in 60-80% of patients under the age of 55 years with a projected long-term disease free survival of 25-50%; the figures for older patients are 25-30% and <15%, respectively. Higher doses with stem cell support have not been associated with major benefit [9]. Clearly new approaches are needed to improve the outlook for these patients

Keywords

Lymphoma Bevacizumab Streptomyces Myeloma Cytosine 

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References

  1. 1.
    Adams, J, Palombella VJ, Sausville EA, Johnson J, Destree A, Lazarus DD, Maas J, Pien CS, Prakash S and Elliott P (1999) Proteasome inhibitors: a novel class of potent and effective antitumor agents. Cancer Res, 59, 2615 – 2622PubMedGoogle Scholar
  2. 2.
    Adams, J and Stein R (1996) Novel inhibitors of the proteasome and their therapeutic use in inflammation. Ann Rep Med Chem, 31, 279 – 288CrossRefGoogle Scholar
  3. 3.
    Beg, AA and Baltimore D (1996) An essential role for NF-KB in preventing TNF-a-induced cell death. Science, 274, 782 – 784PubMedCrossRefGoogle Scholar
  4. 4.
    Boffa, LC, Vidali G, Mann RS and Allfrey VG (1978) Suppression of histone deacetylation in vivoand in vitroby sodium butyrate. J Biol Chem, 253 (10), 3364 – 6PubMedGoogle Scholar
  5. 5.
    Brusilow, SW, Danney M, Waber LJ, Batshaw M, Burton B, Levitsky L, Roth K, McKeethren C and Ward J (1984) Treatment of episodic hyperammonemia in children with inborn errors of urea synthesis. N Engl J Med, 310 (25), 1630 – 4PubMedCrossRefGoogle Scholar
  6. 6.
    Byrd, JC, Shinn C, Ravi R, Willis C, Waselenko JK, Flinn IW,Dawson NA and Grever MR (1999) Depsipeptide (FR901228): a novel therapeutic agent with selective, in vitro activity against human Bcell chronic lymphocytic leukemia cells. Blood, 94, 1401 – 1408PubMedGoogle Scholar
  7. 7.
    Cameron, EE, Bachman KE, Myohanen S, Herman JG and Baylin SB (1999) Synergy of demethylation and histone deacetylase inhibition in the reexpression of genes silenced in cancer. Nat Genet, 21 (1), 103 – 7PubMedCrossRefGoogle Scholar
  8. 8.
    Candido, EP, Reeves R and Davie JR (1978) Sodium butyrate inhibits histone deacetylation in cultured cells. Cell, 14 (1), 105 – 13PubMedCrossRefGoogle Scholar
  9. 9.
    Cassileth, PA, Harrington DP, Appelbaum FR, Lazarus HM, Rowe JM, Paietta E, Willman C, Hurd DD, Bennett JM, Blume KG, Head DR and Wiernik PH (1998) Chemotherapy compared with autologous or allogeneic bone marrow transplantation in the management of acute myeloid leukemia in first remission. New Engl J Med, 339, 1649 – 1656PubMedCrossRefGoogle Scholar
  10. 10.
    Christiansen, I, Gidlöf C, Wallgren A, Simonsson B and Tötterman TH (1994) Serum levels of soluble intercellular adhesion molecule 1 are increased in chronic B-lymphocytic leukemia and correlate with clinical stage and prognostic markers. Blood, 84, 3010 – 3016PubMedGoogle Scholar
  11. 11.
    Christman, JK and et al. (1983) Effect of 5-azacytidine on differentiation and DNA methylation in human promyelocytic leukemia cells (HL-60). Cancer Res., 43 (2), 763 – 9.PubMedGoogle Scholar
  12. 12.
    Collins, AF, Pearson HA, Giardina P, McDonagh KT, Brusilow SW and Dover Gj (1995) Oral sodium phenylbutyrate therapy in homozygous beta thalassemia: a clinical trial. Blood, 85 (l), 43 – 9PubMedGoogle Scholar
  13. 13.
    Cox, AD and Der CJ (1997) Farnesyltransferase inhibitors and cancer treatment: targeting simply Ras? Biochem et Biophys Acta,1333, F51 –F71Google Scholar
  14. 14.
    Creusot, F, Acs G and Christman JK (1982) Inhibition of DNA methyltransferase and induction of Friend erythroleukemia cell differentiation by 5azacytidine and 5-aza-2’- deoxycytidine. J Biol Chem, 257 (4), 2041 – 8PubMedGoogle Scholar
  15. 15.
    David, G, Alland L, Hong SH, Wong CW, DePinho RA and Dejean A (1998) Histone deacetylase associated with mSin3A mediates repression by the acute promyelocytic leukemia-associated PLZF protein. Oncogene, 14, 2549 – 2556CrossRefGoogle Scholar
  16. 16.
    Ellison, RR, Holland JF, Weil M, Jacquillat C, Boiron M, Bernard J, Sawitsky A, Rosner F, Gussoff B, Silver RT, Karanas A, Cuttner J, Spurr CL, Hayes DM, Blom J, Leone LA, Haurani F, Kyle R, Hutchinson JL, Forcier Rj and Moon JH (1968) Arabinosyl cytosine: a useful agent in the treatment of acute leukemia in adults. Blood, 32, 507 – 523PubMedGoogle Scholar
  17. 17.
    Gelmetti, V, Zhang J, Fanelli M, Minucci S, Pelicci PG and Lazar MA (1998) Aberrant recruitment of the nuclear receptor corepressor-histone deacetylase complex by the acute myeloid leukemia fusion partner ETO. Mol Cell Biol, 18, 7185 – 7191PubMedGoogle Scholar
  18. 18.
    Gibbs, JB and Oliff A (1997) The potential of farnesyltransferase inhibitors as cancer therapeutics. Ann Rev Pharmacol Toxicol, 37, 143 – 166CrossRefGoogle Scholar
  19. 19.
    Giles, FJ, Cortes JE, Baker SD, Thomas DA, O’Brien S, Smith TL, Beran M, Bivins C, Jolivet J and Kantarjian HM (2001) Troxacitabine, a novel dioxalone nucleoside analog, has activity in patients with advanced leukemia. J Clin Oncol, 19, 762 – 771PubMedGoogle Scholar
  20. 20.
    Glover, AB, Leyland-jones BR, Chun HG, Davies B and Hoth DF (1987) Azacytidine: 10 years later. Cancer Treat Rep, 71, 737 – 746PubMedGoogle Scholar
  21. 21.
    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 and Pelicci PG (1998) Fusion proteins of the retinoic acid receptor-alpha recruit histone deacetylase in promyelocytic leukaemia. Nature, 391, 8815 – 818Google Scholar
  22. 22.
    Gu, XF, Bikfalvi A, Chen YZ, Caen JP and Han ZC (1995) Constitutive and selective expression of basic fibroblast growth factor in human leukemia cell lines. Eur J Haematol, 55, 189 – 194PubMedCrossRefGoogle Scholar
  23. 23.
    Guidez, F, Ivins S, Zhu J, Soderstrom M, Waxman S and Zelent A (1998) Reduced retinoic acid-sensitivities of nuclear receptor corepressor binding to PML- and PLZF-RAR alpha underlie molecular pathogenesis and treatment of acute promyelocytic leukemia. Blood, 91 (8), 2634 – 42PubMedGoogle Scholar
  24. 24.
    He, LZ, Guidez F, Tribioli C, Peruzzi D, Ruthardt M, Zelent A and Pandolfi PP (1998) Distinct interactions of PML-RAR alpha and PLZF-RAR alpha with co- repressors determine differential responses to RA in APL. Nat Genet, 18 (2), 126 – 35PubMedCrossRefGoogle Scholar
  25. 25.
    König, A, Menzel T, Lynen S, Wrazel L, Rosen A, AlKatib A, Raveche E and Gabrilove JL (1997) Basic fibroblast growth factor (bFGF) upregulates the expression of bcl-2 in B cell chronic lymphocytic leukemia cell lines resulting in delaying apoptosis. Leukemia, 11, 258 – 265PubMedCrossRefGoogle Scholar
  26. 26.
    Lancet, J, Rosenblatt, J, Liesveld, JL, et al: (2000) use of farnesyl transferase inhibitor R115777 in relapsed and refractory acute leukemias: preliminary results of a phase I trial. Proc ASCO, 19, 3a (abstr 5B)Google Scholar
  27. 27.
    Larson, RA, Sweet DL, Golomb HM, Testa JR and Rowley JD (1982) Response to 5-azacytidine in patients with refractory acute nonlymphocytic leukemia and association with chromosome findings. Cancer, 49, 2222 – 2225PubMedCrossRefGoogle Scholar
  28. 28.
    Lin, RJ, Nagy L, Inoue S, Shao W, Miller WH and Evans RM (1998) Role of the histone deacetylase complex in acute promyelocytic leukaemia. Nature, 391, 811 – 814PubMedCrossRefGoogle Scholar
  29. 29.
    Lin, ZP, Boller YC, Amer SM, Russell RL, Pacelli KA, Patierno SR and Kennedy KA (1998) Prevention of brefeldin A-induced resistance to teniposide by the proteasome inhibitor MG-132: involvement of NF--KB activation in drug resistance. Cancer Res, 58, 3059 – 3065PubMedGoogle Scholar
  30. 30.
    Liu, L, Bar-Ner M, Weber J, Danielpour D, Qian SW, Shearer GM and Samid D (1994) Enhancement of tumor immunogenicity by phenylacetate and derivatives: changes in surface antigens and tumorderived immunosuppressive factors. Proc Ann Meet Am Assoc Cancer Res, 35, A2866Google Scholar
  31. 31.
    Liu, L, Shack S, Stetler-Stevenson WG, Hudgins WR and Samid D (1994) Differentiation of cultured human melanoma cells induced by the aromatic fatty acids phenylacetate and phenylbutyrate. J Invest Dermatol, 103 (3), 335 – 40PubMedCrossRefGoogle Scholar
  32. 32.
    Lutterbach, B, Westendorf JJ, Linggi B, Patten A, Moniwa M, Davie JR, Huynh KD, Bardwell VJ, Lavinsky RM, Rosenfeld MG, Glass C, Seto E and Hiebert SW (1998) ETO, a target of t(8;21) in acute leukemia, interacts with the N-CoR and mSin3 corepressors. Mol Cell Biol, 18, 7176 – 7184PubMedGoogle Scholar
  33. 33.
    Maki, C, Huibregtse J and Howley P (1996) In vivo ubiquination and proteasome-mediated degradation of p53. Cancer Res, 56, 2649 – 2654PubMedGoogle Scholar
  34. 34.
    McLaughlin, P, Grillo-L6pez AJ, Link BK, Levy R, Czuczman MS, Williams ME, Heyman MR, BenceBruckler I, White CA, Cabanillas F, Jain V, Ho AD, Lister J, Wey K, Shen D and Dallaire BK (1998) Rituximab chimeric anti-CD20 monoclonal antibody therapy of relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncol, 16, 2825 – 2833PubMedGoogle Scholar
  35. 35.
    Menzel, T, Rahman Z, Calleja E, White K, Wilson EL, Wieder R and Gabrilove J (1996) Elevated intracellular level of basic fibroblast growth factor correlates with stage of chronic lymphocytic leukemia and is associated with resistance to fludarabine. Blood, 87, 1056 – 1063PubMedGoogle Scholar
  36. 36.
    Momparler, RL and Derse D (1979) Kinetics of phosphorylation of 5-aza-2’-deoxycytidine by deoxycytidine kinase. Biochem Pharmacol, 28 (8), 1443 – 4PubMedCrossRefGoogle Scholar
  37. 37.
    Nakajima, H, Kim YB, Terano H, Yoshida M and Horinouchi S (1998) FR901228, a potent antitumor antibiotic, is a novel histone deacetylase inhibitor. Exp Cell Res, 241 (1), 126 – 33PubMedCrossRefGoogle Scholar
  38. 38.
    Nara, N, Kurokawa H, Tohda S, Tomiyama J, Nagata K and Tanikawsa S (1995) The effect of basic and acidic fibroblast growth factors (bFGF and aFGF) on the growth of leukemic blast progenitors in acute myelogenous leukemia. Exp Hematol, 23, 1030 – 1034PubMedGoogle Scholar
  39. 39.
    Orlowski, RZ, Eswara JR, Larond-Walker A, Grever MR, Orlowski M and Dang CV (1998) Tumor growth inhibition induced in a murine model of human Burkitt’’s lymphoma by a proteasome inhibitor. Cancer Res, 58, 4342 – 4348PubMedGoogle Scholar
  40. 40.
    Perez-Atayde, AR, Sallan SE, Tedrow U, Connors S, Allred E and Folkman J (1997) Spectrum of tumor angiogenesis in the bone marrow of children with acute lymphoblastic leukemia. Am J Clin Pathol, 150, 815 – 821Google Scholar
  41. 41.
    Pineau, T, Hudgins WR, Liu L, Chen LC, Sher T, Gonzalez FJ and Samid D (1996) Activation of a human peroxisome proliferator-activated receptor by the antitumor agent phenylacetate and its analogs. Biochem Pharmacol, 52 (4), 659 – 67PubMedCrossRefGoogle Scholar
  42. 42.
    Piro, LD, Carrera CJ, Carson DA and Beutler E (1990) Lasting remissions in hairy cell leukemia induced by a single infusion of 2-chlorodeoxyadenosine. New Engl J Med, 322, 1117 – 1121PubMedCrossRefGoogle Scholar
  43. 43.
    Prasanna, P, Shack S, Wilson VL and Samid D (1994) Phenylacetate and derivatives as novel, nontoxic chemopreventive agents. Proc Ann Meet Am Assoc Cancer Res, 35, 325 (#1935)Google Scholar
  44. 44.
    Richon, VM, Emiliani S, Verdin E, Webb Y, Breslow R, Rifkind RA and Marks PA (1998) A class of hybrid polar inducers of transformed cell differentiation inhibits histone deacetylases. Proc Natl Acad Sci U S A, 95 (6), 3003 – 7PubMedCrossRefGoogle Scholar
  45. 45.
    Rosenfeld, H and Roberts J (1981) Enhancement of antitumor activity of glutamine antagonists 6-diazo5-oxo-L-norleucine and acivicin in cell culture by glutaminase-asparaginase. Cancer Res, 41 (4), 1324 – 8PubMedGoogle Scholar
  46. 46.
    Saiki, JH, Bodey GP, Hewlett JS and al e (1981) Effect of schedule on activity and toxicity of 5azacytidine in acute leukemia. A Southwest Oncology Group study. Cancer, 47, 1739 – 1742PubMedCrossRefGoogle Scholar
  47. 47.
    Saiki, JH, McCredie KB, Vietti TJ, Hewlett JS, Morrison FS, Costanzi JJ, Stuckey WJ and Whitecar J (1978) 5-Azacytidine in acute leukemia. Cancer, 42,2111–2114PubMedCrossRefGoogle Scholar
  48. 48.
    Saito, A, Yamashita T, Mariko Y, Nosaka Y, Tsuchiya K, Ando T, Suzuki T, Tsuruo T and Nakanishi 0 (1999) A synthetic inhibitor of histone deacetylase, MS-27–275, with marked in vivo antitumor activity against human tumors. Proc Natl Acad Sci U S A, 96 (8), 4592 – 7PubMedCrossRefGoogle Scholar
  49. 49.
    Salven, P, Teerenhovi L and Joensuu H (1997) A high pretreatment serum vascular endothelial growth factor concentration is associated with poor outcome in non-Hodgkin’s lymphoma. Blood, 90, 3167 – 3172PubMedGoogle Scholar
  50. 50.
    Samid, D, Hudgins WR, Shack S, Miller AC, Liu L, Prasanna P, Walls R and Myers CE (1994). Phenylacetate and derivatives: simple compounds with complex antitumor activities. In Proc Ann Meet Am Assoc Cancer Res (Vol. 35, pp. #2435).Google Scholar
  51. 51.
    Samid, D, Ram Z, Hudgins WR, Shack S, Liu L, Walbridge S, Oldfield EH and Myers CE (1994) Selective activity of phenylacetate against malignant gliomas: resemblance to fetal brain damage in phenylketonuria. Cancer Res, 54 (4), 891 – 5PubMedGoogle Scholar
  52. 52.
    Schellens, JHM, de Klerk G, Swart M, Palmer PA, Bol CJ, van ’t Veer LJ, Tan H, ten Bokkel Huinink WW and Beijnen JH (1999). Phase I and pharmacologic study with the novel farnesyltransferase inhibitor (FTI) R115777. In 90th Ann Meet Am Assoc Cancer Res (Vol. 40, pp. 724 (A4780)).Google Scholar
  53. 53.
    Sealy, L and Chalkley R (1978) The effect of sodium butyrate on histone modification. Cell, 14 (1), 115 – 21PubMedCrossRefGoogle Scholar
  54. 54.
    Singhal, S, Mehta J, Desikan, R, et al (1998) Antitumor activity of thalidomide in refractory multiple myeloma. New Engl J Med, 341, 156501571Google Scholar
  55. 55.
    Skrzat, S, Angibaud P, Venet M, Sanz G, Bowden C and End D (1998). R115777, a novel imidazole farnesyl protein transferase inhibitor (FTI) with potent oral antitumor activity. In Proc Am Assoc Cancer Res (Vol. 39, pp. A2169 ).Google Scholar
  56. 55.
    Skrzat, S, Angibaud P, Venet M, Sanz G, Bowden C and End D (1998). R115777, a novel imidazole farnesyl protein transferase inhibitor (FTI) with potent oral antitumor activity. In Proc Am Assoc Cancer Res (Vol. 39, pp. A2169 ).Google Scholar
  57. 57.
    Taylor, SM, Constantinides PA and Jones PA (1984) 5-Azacytidine, DNA methylation, and differentiation. Curr Top Microbial Immunol,108,115–27CrossRefGoogle Scholar
  58. 58.
    Vogler, WR, Miller DS and Keller JW (1976) 5-Azacytidine (NSC 102816): A new drug for the treatment of myeloblastic leukemia. Blood, 48, 331–337PubMedGoogle Scholar
  59. 59.
    Wang, C-Y, Cusack JC and Liu R (1999) Control of inducible chemoresistance: enhanced antitumor therapy through increased apoptosis by inhibition of NF-KB. Nature, 5, 412 – 417CrossRefGoogle Scholar
  60. 60.
    Wang, C-Y, Mayo MW and Baldwin AS (1996) TNF- and cancer therapy-induced apoptosis: potentiation by inhibition of NFKB. Science, 274, 784 – 787PubMedCrossRefGoogle Scholar
  61. 61.
    Wang, J, Hoshino T, Redner RL, Kajigaya S and Liu JM (1998) ETO, fusion partner in t(8;21) acute myeloid leukemia, represses transcription by interaction with the human N-CoR/mSin3/HDAC1 complex. Proc Nat Acad Sci, 95, 10860 – 10865PubMedCrossRefGoogle Scholar
  62. 62.
    Warrell, RP, Jr., Frankel SR, Miller WH, Scheinberg DA, Itri LM, Hittelman WN, Vyas R, Andreef M, Tafuri A, Jakubowski A, Gabrilove J, Gordon MS and Dmitrovsky E (1991) Differentiation therapy of acute promyelocytic leukemia with tretinoin (all-trans-retinoic acid). New Engl J Med, 324, 1385 – 1393PubMedCrossRefGoogle Scholar
  63. 63.
    Warrell, RP, Jr., He LZ, Richon V, Calleja E and Pandolfi PP (1998) Therapeutic targeting of transcription in acute promyelocytic leukemia by use of an inhibitor of histone deacetylase [see comments]. J Natl Cancer Inst, 90 (21), 1621 – 5PubMedCrossRefGoogle Scholar
  64. 64.
    Weber, G (1983) Biochemical strategy of cancer cells and the design of chemotherapy: G. H. A. Clowes Memorial Lecture. Cancer Res, 43 (8), 3466 – 92PubMedGoogle Scholar
  65. 65.
    Wood, CG, Lee C, Grayhack JT and Kozlowski JM (1994) Phenylacetate and phenylbutyrate promote cellular differentiation in human prostate cancer systems. Proc Ann Meet Am Assoc Cancer Res, 35, 403 (#2404)Google Scholar
  66. 66.
    Yang, W Del Villar K, Urbano J, Mitsuzawa H and Tamanoi F (1997) Advances in the development of farnesyltransferase inhibitors: substrate recognition by protein farnesyltransferase. J Cell Biochem Suppl, 27, 12 – 19Google Scholar
  67. 67.
    Yoshida, H, Kitamura K, Tanaka K, Omura S, Miyazaki T, Hachiya T, Ohno R and Naoe T (1996) Accelerated degradation of PML-retinoic acid receptor a (PML-RARα) by all-trans retinoic acid in acute promyelocytic leukemia: possible role of the proteasome pathway. Cancer Res, 56, 2945 – 2948PubMedGoogle Scholar
  68. 68.
    Yu, KH, Weng Lj and Gore SD (1997). Augmentation of phenylbutyrate (PB)-induced differentiation of myeloid leukemia cells using retinoic acid. In Proc Ann Meet Am Assoc Cancer Res (Vol. 38, pp. #583).Google Scholar
  69. 69.
    Zujewski, J, Horak ID, Woestenborghs R, Chiao J, Cusack G, Kohler D, Kremer Ab and Cowan KH (1998). Phase I trial of farnesyl-transferase inhibitor, R115777, in advanced cancer. In Proc Ann Meet Am Assoc Cancer Res (Vol. 39, pp. A1848 ).Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2003

Authors and Affiliations

  • B. D. Cheson
    • 1
  1. 1.National Cancer Institute, Executive Plaza North - Rm 741BethesdaUSA

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