46
Views
15
CrossRef citations to date
0
Altmetric
Review

Emerging treatments in acute myeloid leukaemia

Pages 55-71 | Published online: 02 Mar 2005

Bibliography

  • LOWENBERG B, DOWNING JR, BURNETT A: Acute myeloid leukemia. N. Engl. J. Med. (1999) 341(14):1051–1062; Erratum appears in N Engl. I Med. (1999) 341(19):1484. Comprehensive review of AML.
  • ROWE JM: What is the best induction regimen for acute myelogenous leukemia? Leukemia (1998) 12\(Suppl. 1):S16–S19.
  • HANN IM, STEVENS RF, GOLDSTONE AH et al: Randomized comparison of DAT versus ADE as induction chemotherapy in children and younger adults with acute myeloid leukemia. Results of the Medical Research Council's 10th AML trial (MRC AML10). Adult and Childhood Leukaemia Working Parties of the Medical Research Council. Blood (1997) 89(7):2311–2318. Results of the MRC 10 trial.
  • ZITTOUN R, SUCIU S, WATSON M et al.: Quality of life in patients with acute myelogenous leukemia in prolonged first complete remission after bone marrow transplantation (allogeneic or autologous) or chemotherapy: a cross-sectional study of the EORTC-GIMEMA AML 8A trial. Bone Marrow Transplant (1997) 20(4):307-3l5.
  • MAYER RJ, DAVIS RB, SCHIFFER CA et al.: Intensive postremission chemotherapy in adults with acute myeloid leukemia. Cancer and Leukemia Group B. N Engl. Med. (1994) 331(14):896–903.
  • BERMAN E: Chemotherapy in acute myelogenous leukemia: high dose, higher expectations?' Olin Oncol (1995) 13(1):1–4.
  • ROWE JM, TALLMAN MS: Intensifying induction therapy in acute myeloid leukemia: has a new standard of care emerged? Blood (1997) 90(6):2121–2126.
  • BISHOP JF, LOWENTHAL RM, JOSHUA D et al.: Etoposide in acute nonlymphocytic leukemia. Australian Leukemia Study Group. Blood (1990) 75(1):27–32.
  • VOGLER WR, VELEZ-GARCIA E, WEINER RS et al.: A Phase III trial comparing idarubicin and daunorubicin in combination with cytarabine in acute myelogenous leukemia: a Southeastern Cancer Study Group Study. I Clin. Oncol. (1992) 10(7):1103–1111.
  • WIERNIK PH, BANKS PL, CASE DC Jr et al.: Cytarabine plus idarubicin or daunorubicin as induction and consolidation therapy for previously untreated adult patients with acute myeloid leukemia. Blood (1992) 79(2):313–319.
  • MANDELLI F, PETTI MC, ARDIA A et al.: A randomised clinical trial comparing idarubicin and cytarabine to daunorubicin and cytarabine in the treatment of acute non-lymphoid leukaemia. A multicentric study from the Italian Co-operative Group GIMEMA. Eur. J. Cancer (1991) 27(6):750–755.
  • BERMAN E, HELLER G, SANTORSA J et al.: Results of a randomized trial comparing idarubicin and cytosine arabinoside with daunorubicin and cytosine arabinoside in adult patients with newly diagnosed acute myelogenous leukemia. Blood (1991) 77(8):1666–1674.
  • ARLIN Z, CASE DC, Jr, MOORE J et al: Randomized multicenter trial of cytosine arabinoside with mitoxantrone or daunorubicin in previously untreated adult patients with acute nonlymphocytic leukemia (ANLL). Lederle Cooperative Group. Leukemia (1990) 4(3):177–183.
  • LOWENBERG B, SUCIU S, ARCHIMBAUD E et al: Mitoxantrone versus daunorubicin in induction-consolidation chemotherapy-the value of low-dose cytarabine for maintenance of remission, and an assessment of prognostic factors in acute myeloid leukemia in the elderly: final report. European Organization for the Research and Treatment of Cancer and the Dutch-Belgian Hemato-Oncology (Huntingt) Cooperative Hovon Group. Clin. Oncol. (1998) 16(3):872–881.
  • AML COLLABORATIVE GROUP: A systematic collaborative overview of randomized trials comparing idarubicin with daunorubicin (or other anthracyclines) as induction therapy for acute myeloid leukaemia. BE J. Haematol (1998) 103(1):100–109.
  • ROWE JM, NEUBERG D, results of a Phase II study. Blood (2002) 99(6):1928–1937.
  • DRUKER BJ, SAWYERS CL, KANTARJIAN H et al.: Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome. N. Engl. J. Med. (2001) 344(14):1038–1042; Erratum appears in N. Engl. J. Med. (2001) 345(3):232.
  • DRUKER BJ, TALPAZ M, RESTA DJ et al.: Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl. Med. (2001) 344(14):1031–1037.
  • Lancet JE, KARP JE: Farnesyltransferase inhibitors in hematologic malignancies: new horizons in therapy. Blood (2003) 102(12):3880–3889.
  • ••A thorough review of FTIs.
  • ASHAR HR, JAMES L, GRAY K et al: Farnesyl transferase inhibitors block the farnesylation of CENP-E and CENP-F and alter the association of CENP-E with the microtubules. J. Biol. Chem. (2000) 275(39):30451–30457.
  • LEBOWITZ PF, PRENDERGAST GC: Non-Ras targets of farnesyltransferase inhibitors: focus on Rho. Oncogene (1998) 17(11 Reviews):1439–1445.
  • CORTES JE, KURZROCK R, KANTARJIAN HM: Farnesyltransferase inhibitors: novel compounds in development for the treatment of myeloid malignancies. Semin. Hematol (2002) 39(3, Suppl. 2):26–30.
  • END DW: Farnesyl protein transferase inhibitors and other therapies targeting the Ras signal transduction pathway. Invest. New Drugs (1999) 17(3):241–258.
  • ROWINSKY EK, WINDLE JJ, VON HOFF DD: Ras protein farnesyltransferase: A strategic target for anticancer therapeutic development. J. Clin. Oncol (1999) 17(10:3631–3652.
  • PRENDERGAST GC: Farnesyltransferase inhibitors define a role for RhoB in controlling neoplastic pathophysiology. Histol Histopathol (2001) 16(1):269–275.
  • ADNANE J, SEIJO E, CHEN Z et al: RhoB, not RhoA, represses the transcription of the transforming growth factor beta type II receptor by a mechanism involving activator protein 1. J. Biol. Chem. (2002) 277(10):8500–8507.
  • BOS JL: ras oncogenes in human cancer: a review. Cancer Res. (1989) 49(17):4682–4689; Erratum appears in Cancer Res. (1990) 50(4):1352.
  • BEAUPRE DM, KURZROCK R: RAS and leukemia: from basic mechanisms to gene-directed therapy../. Clin. Oncol (1999) 17(3):1071–1079.
  • PATNAIK A, ROWINSKY EK: Early clinical experience with farnesyl protein transferase inhibitors: from the bench to the bedside. In: Fanesyl Transferase Inhibitors in Cancer Therapy. Sebti SM, Hamilton AD (Eds), Humana Press, Totowa, NJ, USA (2001): 233–249.
  • MANNE V, YAN N, CARBONI JM et al: Bisubstrate inhibitors of farnesyltransferase: a novel class of specific inhibitors of ras transformed cells. Oncogene (1995) 10(9):1763–1779.
  • ZUJEWSKI J, HORAK ID, BOL CJ et al.: Phase I and pharmacokinetic study of farnesyl protein transferase inhibitor R115777 in advanced cancer. J. Clin. Oncol (2000) 18(4):927–941.
  • WRIGHT J, BLATNER GL, CHESON BD: Clinical trials referral resource. Clinical trials with the farnesyl transferase inhibitor RU 5777. Oncology aluntingt) (1999) 13(11):1527.
  • PUNT CJ, VAN MAANEN L, BOL CJ, SEIFERT WE WAGENER DJ: Phase I and pharmacokinetic study of the orally administered farnesyl transferase inhibitor R115777 in patients with advanced solid tumors. Anticancer Drugs (2001) 12(3):193–197.
  • END DW, SMETS G, TODD AV et al: Characterization of the antitumor effects of the selective farnesyl protein transferase inhibitor RU 5777 in vivo and in vitro. Cancer Res. (2001) 61(1):131–137.
  • KELLAND LR, SMITH V, VALENTI M et al.: Preclinical antitumor activity and pharmacodynamic studies with the farnesyl protein transferase inhibitor R115777 in human breast cancer. Clin. Cancer Res. (2001) 7(11):3544–3550.
  • ZHANG B, PRENDERGAST GC, FENTON RG: Farnesyltransferase inhibitors reverse Ras-mediated inhibition of Fas gene expression. Cancer Res. (2002) 62(2):450–458.
  • CORTES J, ALBITAR M, THOMAS D et al.: Efficacy of the farnesyl transferase inhibitor R115777 in chronic myeloid leukemia and other hematologic malignancies. Blood (2003) 101(5):1692–1697.
  • REICHERT A, HEISTERKAMP N, DALEY GQ, GROFFEN J: Treatment of Bcr/Abl-positive acute lymphoblastic leukemia in P190 transgenic mice with the farnesyl transferase inhibitor 5CH66336. Blood (2001) 97(5):i399–i403.
  • PETERS DG, HOOVER RR, GERLACH MJ et al.: Activity of the farnesyl protein transferase inhibitor 5CH66336 against BCR/ABL-induced murine leukemia and primary cells from patients with chronic myeloid leukemia. Blood (2001) 97(5):1404–1412.
  • HUNT JT, DING CZ, BATORSKY R et al: Discovery of (R)-7-cyano-2,3,4, 5-tetrahydro-1- (1H-imidazol-4-ylmethyl) - 3- Iphenylmethy9-4-(2-thienylsulfony9-1H-1, 4-benzodiazepine (BMS-214662), a farnesyltransferase inhibitor with potent preclinical antitumor activity. J. Med. Chem. (2000) 43(20):3587–3595.
  • ROSE WC, LEE FY, FAIRCHILD CR et al.: Preclinical antitumor activity of BMS-214662, a highly apoptotic and novel farnesyltransferase inhibitor. Cancer Res. (2001) 61(20):7507–7517.
  • SUN J, BLASKOVICH MA, KNOWLES D et al: Antitumor efficacy of a novel class of non-thiol-containing peptidomimetic inhibitors of farnesyltransferase and geranylgeranyltransferase I: combination therapy with the cytotoxic agents cisplatin, Taxol, and gemcitabine. Cancer Res. (1999) 59(19):4919–4926.
  • MORGAN MA, DOLP O, REUTER CW: Cell-cycle-dependent activation of mitogen-activated protein kinase kinase (MEK-1/2) in myeloid leukemia cell lines and induction of growth inhibition and apoptosis by inhibitors of RAS signaling. Blood (2001) 97(6):1823–1834.
  • REUTER CW, MORGAN MA, WEGNER J, GANSER A: Induction of growth inhibition and apoptosis by FTase and GGTase inhibitors in myeloid leukemia cells. Blood (2001) 98(11):432a.
  • JAMES G, GOLDSTEIN JL, BROWN MS: Resistence K-RasBV12 proteins to farnesyltransferase inhibitors in ratl cells. Proc. Nati Acad. Sci. USA (1996) 93(9):4454–4458.
  • ROWELL CA, KOWALCZYK JJ, LEWIS MD, GARCIA AM: Direct demonstration of geranylgeranylation and farnesylation of Ki-Ras in vivo. J. Biol. Chem. (1997) 272(22):14093–14097.
  • WHYTE DB, KIRSCHMEIER P, HOCKENBERRY TN et al: K- and N-Ras are geranylgeranylated in cells treated with farnesyl protein transferase inhibitors. ./. Biol. Chem. (1997) 272(22):14459–14464.
  • REUTER CW, WEGNER J, MORGAN MA, GANSER A: Co-treating AML cells with FTI potentiates apoptosis induced by topoisomerase II inhibitors. Blood (2003) 100(11): 542a.
  • MEDEIROS BC, LANDAU HA, MORROW MC, ECKHARDT SG: The farnesyl transferase inhibitor Zarnestra (R115777) exhibits a dual mechanism of action against P-glycoprotein overexpressing leukemia cell lines. Blood (2003) 102(11):610a.
  • AGNES F, SHAMOON B, DINA C et al:Genomic structure of the downstream part of the human FLT3 gene: exon/intron structure conservation among genes encoding receptor tyrosine kinases (RTK) of subclass III. Gene (1994) 145(2):283–288.
  • ROSNET O, STEPHENSON D, MATTEI MG et al.: Close physical linkage of the FLTI and FLT3 genes on chromosome 13 in man and chromosome 5 in mouse. Oncogene (1993) 8(1):173–179.
  • SMALL D, LEVENSTEIN M, KIM E et al.: STK-1, the human homolog of Flk-2/ Flt-3, is selectively expressed in CD34* human bone marrow cells and is involved in the proliferation of early progenitor/stem cells. Proc. Natl. Acad. Li. USA (1994) 91(2):459–463.
  • GOTZE KS, RAMIREZ M, TABOR K et al.: Flt3high and Flt3low CD34* progenitor cells isolated from human bone marrow are functionally distinct. Blood (1998) 91(6):1947–1958.
  • SITNICKA E, BUZA-VIDAS N, LARSSON S et al: Human CD34' hematopoietic stem cells capable of multilineage engrafting NOD/SCID mice express flt3: distinct flt3 and c-kit expression and response patterns on mouse and candidate human hematopoietic stem cells. Blood (2003) 102(3):881–886.
  • MACKAREHTSCHIAN K, HARDIN JD, MOORE KA et al.: Targeted disruption of thel7k2/17t3 gene leads to deficiencies in primitive hematopoietic progenitors. ImmuniO, (1995) 3(1):147–161.
  • LYMAN SD, JACOBSEN SE: c-kit ligand and F1t3 ligand: stem/progenitor cell factors with overlapping yet distinct activities. Blood (1998) 91(4):1101–1134.
  • KIYOI H, NAOE T, YOKOTA S et al.: Internal tandem duplication of FLT3 associated with leukocytosis in acute promyelocytic leukemia. Leukemia Study Group of the Ministry of Health and Welfare (Kohseisho). Leukemia (1997) 11(9):1447–1452.
  • KOTTARIDIS PD, GALE RE, FREW ME et al: The presence of a FLT3 internal tandem duplication in patients with acute myeloid leukemia (AML) adds important prognostic information to cytogenetic risk group and response to the first cycle of chemotherapy: analysis of 854 patients from the United Kingdom Medical Research Council AML 10 and 12 trials. Blood (2001) 98(6):1752–1759.
  • ••Large analysis of the influence of FLT-3mutations on prognosis.
  • JAMAL R, TAKETANI T, TAKI T et al: Coduplication of the MLL and FLT3 genes in patients with acute myeloid leukemia. Genes, Chromosomes & Cancer (2001) 31(2):187–190.
  • STONE RM, KLIMEK V, DEANGELO DJ et al: PKC412, an oral FLT3 inhibitor, has activity in mutant FLT3 acute myeloid leukemia (AML): a Phase II clinical trial. Blood (2002) 101(11): 86a.
  • GILLILAND DG, GRIFFIN JD: The roles of FLT3 in hematopoiesis and leukemia. Blood (2002) 100(5):1532–1542.
  • CAROW CE, LEVENSTEIN M, KAUFMANN SH et al: Expression of the hematopoietic growth factor receptor FLT3 (STK-1/F1k2) in human leukemias. Blood (1996) 87(3):1089–1096.
  • BIRG F, COURCOUL M, ROSNET 0 et al: Expression of the FMS/KIT-like gene FLT3 in human acute leukemias of the myeloid and lymphoid lineages. Blood (1992) 80(10):2584–2593.
  • BIRG F, ROSNET O, CARBUCCIA N, BIRNBAUM D: The expression of FMS, KIT and FLT3 in hematopoietic malignancies. Leukemia & Lymphoma (1994) 13(3-4):223–227.
  • STACCHINI A, FUBINI L, SEVERINO A et al.: Expression of Type III receptor tyrosine kinases FLT3 and KIT and responses to their ligands by acute myeloid leukemia blasts. Leukemia (1996) 10(10):1584–1591.
  • DREXLER HG: Expression of FLT3 receptor and response to FLT3 ligand by leukemic cells. Leukemia (1996) 10(4):588–599.
  • HAYAKAWA F, TOWATARI M, KIYOI H et al.: Tandem-duplicated F1t3 constitutively activates STAT5 and MAP kinase and introduces autonomous cell growth in IL-3-dependent cell lines. Oncogene (2000) 19(5):624–631.
  • MIZUKI M, FENSKI R, HALFTER H et al.: F1t3 mutations from patients with acute myeloid leukemia induce transformation of 32D cells mediated by the Ras and STAT5 pathways. Blood (2000) 96(12):3907–3914.
  • LYMAN SD: Biology of flt3 ligand and receptor. Int. J. Hematol (1995) 62(2):63–73.
  • MCKENNA HJ, SMITH FO, BRASEL K et al.: Effects of flt3 ligand on acute myeloid and lymphocytic leukemic blast cells from children. Exp. Hematol (1996) 24(2)378–385.
  • LISOVSKY M, ESTROV Z, ZHANG X et al.: FLT3 ligand stimulates proliferation and inhibits apoptosis of acute myeloid leukemia cells: regulation of Bc1-2 and Bax. Blood (1996) 88(10):3987–3997.
  • DEHMEL U, ZABORSKI M, MEIERHOFF G et al: Effects of FLT3 ligand on human leukemia cells. I. Proliferative response of myeloid leukemia cells. Leukemia (1996) 10(2):261–270.
  • NAKAO M, YOKOTA S, IWAI T et al: Internal tandem duplication of the flt3 gene found in acute myeloid leukemia. Leukemia (1996) 10(12):1911–1918.
  • YOKOTA S, KIYOI H, NAKAO M et al: Internal tandem duplication of the FLT3 gene is preferentially seen in acute myeloid leukemia and myelodysplastic syndrome among various hematological malignancies. A study on a large series of patients and cell lines. Leukemia (1997) 11(10):1605–1609.
  • FROHLING S, SCHLENK RE BREITRUCK J et al.: Prognostic significance of activating FLT3mutations in younger adults (16 to 60 years) with acute myeloid leukemia and normal cytogenetics: a study of the AML Study Group Ulm. Blood (2002) 100(13):4372–4380.
  • MIZUKI M, SCHWABLE J, STEUR C et al.: Suppression of myeloid transcription factors and induction of STAT response genes by AML-specific F1t3 mutations. Blood (2003) 101(8):3164–3173.
  • KIYOI H, OHNO R, UEDA R, SAITO H, NAOE T: Mechanism of constitutive activation of FLT3 with internal tandem duplication in the juxtamembrane domain. Oncogene (2002) 21(16):2555–2563.
  • STIREWALT DL, KOPECKY KJ, MESHINCHI S et al: FLT3, RAS, and TP53 mutations in elderly patients with acute myeloid leukemia. Blood (2001) 97(11):3589–3595; Erratum appears in Blood (2001) 98(4):924.
  • ABU-DUHIER FM, GOODEVE AC, WILSON GA et al: FLT3 internal tandem duplication mutations in adult acute myeloid leukaemia define a high-risk group. Br. J. Haematol (2000) 111(1):190–195.
  • WHITMAN SP, ARCHER KJ, FENG L et al: Absence of the wild-type allele predicts poor prognosis in adult de novo acute myeloid leukemia with normal cytogenetics and the internal tandem duplication of FLT3 a cancer and leukemia group B study. Cancer Res. (2001) 61(19):7233–7239.
  • ROMBOUTS WJ, MARTENS AC, PLOEMACHER RE: Identification of variables determining the engraftment potential of human acute myeloid leukemia in the immunodeficient NOD/SCID human chimera model. Leukemia (2000) 14(5):889–897.
  • KIYOI H, NAOE T, NAKANO Y et al: Prognostic implication of FLT3 and N- 14S gene mutations in acute myeloid leukemia. Blood (1999) 93(9):3074–3080.
  • ROMBOUTS WJ, BLOKLAND I, LOWENBERG B, PLOEMACHER RE: Biological characteristics and prognosis of adult acute myeloid leukemia with internal tandem duplications in the f-it3 gene. Leukemia (2000) 14(4):675–683.
  • YAMAMOTO Y, KIYOI H, NAKANO Y et al.: Activating mutation of D835 within the activation loop of FLT3 in human hematologic malignancies. Blood (2001) 97(8):2434–2439.
  • ABU-DUHIER FM, GOODEVE AC, WILSON GA et al: Identification of novel FLT-3Asp835 mutations in adult acute myeloid leukaemia. BE J. Haematol (2001) 113(4):983–988.
  • ANDREWS RG, TOROK-STORB B, BERNSTEIN ID: Myeloid-associated differentiation antigens on stem cells and their progeny identified by monoclonal antibodies. Blood (1983) 62(1):124–132.
  • ULYANOVA T, BLASIOLI J, WOODFORD-THOMAS TA, THOMAS ML: The sialoadhesin CD33 is a myeloid-specific inhibitory receptor. Eur. Immunol (1999) 29(10:3440–3449.
  • GRIFFIN JD, LINCH D, SABBATH K, LARCOM P, SCHLOSSMAN SF: A monoclonal antibody reactive with normal and leukemic human myeloid progenitor cells. Leuk. Res. (1984) 8(4):521–534.
  • DINNDORF PA, ANDREWS RG, BENJAMIN D et al.: Expression of normal myeloid-associated antigens by acute leukemia cells. Blood (1986) 67(4):1048–1053.
  • PEIPER SC, ASHMUN RA, LOOK AT: Molecular cloning, expression, and chromosomal localization of a human gene encoding the CD33 myeloid differentiation antigen. Blood (1988) 72(1):314–321.
  • JILANI I, ESTEY E, HUH Y et al: Differences in CD33 intensity between various myeloid neoplasms. Am. J. Clin. Patna (2002) 118(4):560–566.
  • ZAGURSKY RJ, SHARP D, SOLOMON KA, SCHWARTZ A: Quantitation of cellular receptors by a new immunocytochemical flow cytometry technique. Biotechniques (1995) 18(3):504–509.
  • SCHWARTZ A, MARTI GE, POON R, GRATAMA JW, FERNANDEZ-REPOLLET E: Standardizing flow cytometry: a classification system of fluorescence standards used for flow cytometry. Cytometry (1998) 33(2):106–114.
  • APPELBAUM FR, MATTHEWS DC, EARY JF et al: The use of radiolabeled anti-CD33 antibody to augment marrow irradiation prior to marrow transplantation for acute myelogenous leukemia. Transplantation (1992) 54(5):829–833.
  • TALLMAN MS: Monoclonal antibody therapies in leukemias. Semi]. Hematol (2002) 39(4, Suppl. 3):12–19.
  • BROSS PF, BEITZ J, CHEN G et al: Approval summary: gemtuzumab ozogamicin in relapsed acute myeloid leukemia. Clin. Cancer Res. (2001) 7(6):1490–1496; Erratum appears in Clin. Cancer Res. (2002) 8(1):300.
  • ZEIN N, SINHA AM, MCGAHREN WJ, ELLESTAD GA: Calicheamicin gamma 11: an antitumor antibiotic that cleaves double- stranded DNA site specifically. Science (1988) 240(4856):1198–1201.
  • VAN DER VELDEN VH, MARVELDE JG, HOOGEVEEN PG et al: Targeting of the CD33-calicheamicin immunoconjugate Mylotarg (CMA-676) in acute myeloid leukemia: in vivo and in vitro saturation and internalization by leukemic and normal myeloid cells. Blood (2001) 97(10):3197–3204.
  • HAMANN PR, HINMAN LM, HOLLANDER I et al: Gemtuzumab ozogamicin, a potent and selective anti-CD33 antibody-calicheamicin conjugate for treatment of acute myeloid leukemia. Bioconjug. Chem. (2002) 13(1):47–58.
  • NICOLAOU KC, STABILA P, ESMAELI-AZAD B, WRASIDLO W, HIATT A: Cell-specific regulation of apoptosis by designed enediynes. Proc. Natl. Acad. Sci. USA (1993) 90(8):3142–3146.
  • TREISH IM: Drug update. Targeting leukemia cells with gemtuzumab ozogamicin. Cancer Pract (2000) 8(5):254–256.
  • SIEVERS EL, APPELBAUM FR, SPIELBERGER RT et al.: Selective ablation of acute myeloid leukemia using antibody-targeted chemotherapy: a Phase I study of an anti-CD33 calicheamicin immunoconjugate. Blood (1999) 93(11):3678–3684.
  • BERNSTEIN ID: Monoclonal antibodies to the myeloid stem cells: therapeutic implications of CMA-676, a humanized anti-CD33 antibody calicheamicin conjugate. Leukemia (2000) 14(3):474–475.
  • VAN DER JAGT RH, BADGER CC, APPELBAUM FR et al.: Localization of radiolabeled antimyeloid antibodies in a human acute leukemia xenograft tumor model. Cancer Res. (1992) 52(1):89–94.
  • GILES FJ: Gemtuzumab ozogamicin: promise and challenge in patients with acute myeloid leukemia. Expert Review of Anti-Cancer Therapy (2002) 2(6):630–640.
  • BIRD A: DNA methylation patterns and epigenetic memory. Genes & Development (2002) 16(1):6–21.
  • XU GL, BESTOR TH, BOURCHIS D et al: Chromosome instability and immunodeficiency syndrome caused by mutations in a DNA methyltransferase gene. Nature (1999) 402(6758):187–191.
  • EDEN A, GAUDET F, WAGHMARE A, JAENISCH R: Chromosomal instability and tumors promoted by DNA hypomethylation. Science (2003) 300(5618):455.
  • MOMPARLER RL, BOVENZI V: DNA methylation and cancer. J. Cell. Physiol (2000) 183(2):145–154.
  • BEARZATTO A, SZADKOWSKI M,MACPHERSON P, JIRICNY J, KARRAN P: Epigenetic regulation of the MGMT and hMSH6 DNA repair genes in cells resistant to methylating agents.
  • HIEBERT SW, LUTTERBACH B, AMANN J: Role of co-repressors in transcriptional repression mediated by the t(8;21), t(16;21), t(12;21), and inv(16) fusion proteins. Curr. Opia Hematol
  • KARP JE, LANCET JE, KAUFMANN SH et al.: Clinical and biologic activity of the farnesyltransferase inhibitor R115777 in adults with refractory and relapsed acute leukemias: a Phase I clinical-laboratory
  • HAROUSSEAU JL, REIFFERS J, LOWENBERG B et al: ZarnestraTm (R115777) in patients with relapsed and study. Blood (2003) 102(11):176a.
  • LANCET JE, GOJO I, GOTLIB J et al: Tipifarnib (ZarnestraTm) in previously untreated poor-risk AML and MDS: interim results of a Phase II trial. Blood
  • FELDMAN EJ, CORTES J, HOLYOAKE TL et al: Continuous oral Lonafarnib (SarasarTm) for the treatment of patients with myelodysplastic syndrome. Blood (2003) 102(11): 421a. Semin. Hematol (2002) 39(4, Suppl. 3):20–24.
  • SAWYERS CL: Finding the next Gleevec: FLT3 targeted kinase inhibitor therapy for acute myeloid leukemia. Cancer Cell (2002) 1(5):413–415.
  • YAISH P, GAZIT A, GILON C, LEVITZKI A: Blocking of EGF-dependent cell proliferation by EGF receptor kinase inhibitors. Science (1988) 242(4880):933–935.
  • LEVIS M, TSE KF, SMITH BD, GARRETT E, SMALL D: A FLT3 tyrosine kinase inhibitor is selectively cytotoxic to acute myeloid leukemia blasts harboring FLT3 internal tandem duplication mutations. Blood (2001) 98(3):885–887.
  • TSE KF, NOVELLI E, CIVIN CI, BOHMER FD, SMALL D: Inhibition of FLT3-mediated transformation by use of a tyrosine kinase inhibitor. Leukemia (2001) 15(7):1001–1010.
  • TSE KF, ALLEBACH J, LEVIS M et al: Inhibition of the transforming activity of FLT3 internal tandem duplication mutants from AML patients by a tyrosine kinase inhibitor. Leukemia (2002) 16(10):2027–2036.
  • MESTERS RIVI, PADRO T, BIEKER R et al: Stable remission after administration of the receptor tyrosine kinase inhibitor SU5416 in a patient with refractory acute myeloid leukemia. Blood (2001) 98(1):241–243.
  • YEE KW, O'FARRELL AM, SMOLICH BD et al: 5U5416 and 5U5614 inhibit kinase activity of wild-type and mutant FLT3 receptor tyrosine kinase. Blood (2002) 100(8):2941–2949.
  • SMOLICH BD, YUEN HA, WEST KA et al: The antiangiogenic protein kinase inhibitors 5U5416 and 5U6668 inhibit the SCF receptor (c-kit) in a human myeloid leukemia cell line and in acute myeloid leukemia blasts. Blood (2001) 97(5):1413–1421.
  • STOPECK A, SHELDON M, VAHEDIAN M et al: Results of a Phase I dose-escalating study of the antiangiogenic agent, 5U5416, in patients with advanced malignancies. Clin. Cancer Res. (2002) 8(9):2798–2805.
  • GILES FJ, STOPECK AT, SILVERMAN LR et al: 5U5416, a small molecule tyrosine kinase receptor inhibitor, has biologic activity in patients with refractory acute myeloid leukemia or myelodysplastic syndromes. Blood (2003) 102(3):795–801.
  • KNUSEL B, HEFTI F: K-252 compounds: modulators of neurotrophin signal transduction. J. Neurochem. (1992) 59(6):1987–1996.
  • ZHENG R, FRIEDMAN AD, SMALL D: Targeted inhibition of FLT3 overcomes the block to myeloid differentiation in 32Dc13 cells caused by expression of FLTNITD mutations. Blood (2002) 100(12):4154–4161.
  • LEVIS M, ALLEBACH J, uSE KF et al: A FLT3-targeted tyrosine kinase inhibitor is cytotoxic to leukemia cells in vitro and in vivo. Blood (2002) 99(11):3885–3891.
  • WEERARATNA AT, DALRYMPLE SL, LAMB JC et al.: Pan-trk inhibition decreases metastasis and enhances host survival in experimental models as a result of its selective induction of apoptosis of prostate cancer cells. Clin. Cancer Res. (2001) 7(8):2237–2245.
  • RUGGERI BA, MIKNYOCZKI SJ, SINGH J, HUDKINS RL: Role of neurotrophin-trk interactions in oncology: the anti-tumor efficacy of potent and selective trk tyrosine kinase inhibitors in pre-clinical tumor models. Curl: Med. Chem. (1999) 6(9):845–857.
  • MIKNYOCZKI SJ, CHANG H, KLEIN-SZANTO A, DIONNE CA, RUGGERI BA: The Trk tyrosine kinase inhibitor CEP-701 (KT-5555) exhibits significant antitumor efficacy in preclinical xenograft models of human pancreatic ductal adenocarcinoma. Clin. Cancer Res. (1999) 5(8):2205–2212.
  • MIKNYOCZKI SJ, DIONNE CA, KLEIN-SZANTO AJ, RUGGERI BA: The novel Trk receptor tyrosine kinase inhibitor CEP-701 (KT-5555) exhibits antitumor efficacy against human pancreatic carcinoma (Pancl) xenograft growth and in vivo invasiveness. Ann. NY Acad. ScL (1999) 880:252–262.
  • GEORGE DJ, DIONNE CA, JANI J et al.: Sustained in vivo regression of Dunning H rat prostate cancers treated with combinations of androgen ablation and Trk tyrosine kinase inhibitors, CEP-751 (KT-6587) or CEP-701 (KT-5555). Cancer Res. (1999) 59(10):2395–2401.
  • LEVIS MJ, PHAM R, SMALL D: CEP-701, a selective FLT3 tyrosine kinase inhibitor that is cytotoxic to FLT3/ ITS-expressing leukemia cells, is synergistic with chemotherapeutic agents in vivo when used in time-sequential fashion. Blood (2003) 102(11):66a.
  • DE ANGELO DJ, STONE RIVI, BRUNNER RJ et al.: Phase I clinical results with MLN518, a novel FLT3 antagonist: tolerability, pharmacokinetics, and pharmacodynamics. Blood (2003) 102(11):65a.
  • HEINRICH MC, YEE KW, GIESE NA, SCHITTENHELM M: MLN518, a potent FLT3 inhibitor, displays synergistic effects with cytarabine and daunorubicin on FLT3-ITD leukemia cell lines. Blood (2003) 102(11):97a.
  • KELLY LM, YU JC, BOULTON CL et al: CT53518, a novel selective FLT3 antagonist for the treatment of acute myelogenous leukemia (AML). Cancer Cell (2002) 1(5):421–432.
  • WEISBERG E, BOULTON C, KELLY LM et al: Inhibition of mutant FLT3 receptors in leukemia cells by the small molecule tyrosine kinase inhibitor PKC412. Cancer Cell (2002) 1(5)433–443.
  • STONE RIVI, KLIMEK V, DEANGELO DJ et al: PKC412, an oral FLT3 inhibitor, has activity in mutant FLT3 acute myeloid leukemia (AML): a Phase II clinical trial. Blood (2002) 101(11):86a.
  • KNAPPER S, BURNETT AK, GILKES AF et al: The in vitro sensitivity of primary AML blasts to two FLT-3 inhibitors and cytarabine appears independent of flt-3 mutation status. Blood (2003) 102(11):24a.
  • GAZIT A, APP H, MCMAHON G et al: Tyrphostins 5. Potent inhibitors of platelet-derived growth factor receptor tyrosine kinase: structure-activity relationships in quinoxalines, quinolines, and indole tyrphostins. J. Med. Chem. (1996) 39(11):2170–2177.
  • KOVALENKO M, GAZIT A, BOHMER A et al: Selective platelet-derived growth factor receptor kinase blockers reverse sis-transformation. Cancer Res. (1994) 54(23):6106–6114.
  • SIEVERS EL, LARSON RA, STADTMAUER EA et al.: Efficacy and safety of gemtuzumab ozogamicin in patients with CD33-positive acute myeloid leukemia in first relapse. J. Clin. Oncol (2001) 19(13):3244–3254.
  • •First results with gemtuzumab as single agent in relapsed AML.
  • LARSON RA, BOOGAERTS M, ESTEY E et al.: Antibody-targeted chemotherapy of older patients with acute myeloid leukemia in first relapse using Mylotarg (gemtuzumab ozogamicin). Leukemia (2002) 16(9):1627–1636.
  • GILES FJ, KANTARJIAN HM, KORNBLAU SM et al: Mylotarg (gemtuzumab ozogamicin) therapy is associated with hepatic venoocclusive disease in patients who have not received stem cell transplantation. Cancer (2001) 92(2):406–413.
  • RAJVANSHI P, SHULMAN HM, SIEVERS EL, MCDONALD GB: Hepatic sinusoidal obstruction after gemtuzumab ozogamicin (Mylotarg) therapy. Blood (2002) 99(7)2310-2314; Erratum appears in Blood (2002) 99(11):3915.
  • COHEN AD, LUGER SM, SICKLES C et al.: Gemtuzumab ozogamicin (Mylotarg) monotherapy for relapsed AML after hematopoietic stem cell transplant: Efficacy and incidence of hepatic veno-occlusive disease. Bone Marrow Transplant (2002) 30(1):23–28.
  • SIEVERS E, LARSON R, ESTEY E et al: Final report of prolonged disease-free survival in patients with acute myeloid leukemia in first relapse treated with gemtuzumab ozogamicin followed by haematopoietic stem cell transplant. Blood (2002) 100(11):89a.
  • WADLEIGH M, RICHARDSON PG, ZAHRIEH D et al: Prior gemtuzumab ozogamicin exposure significantly increases the risk of veno-occlusive disease in patients who undergo myeloablative allogeneic stem cell transplantation. Blood (2003) 102(5):1578–1582.
  • BEARMAN SI, ANDERSON GL, MORI M et al: Venoocclusive disease of the liver: development of a model for predicting fatal outcome after marrow transplantation. ./. Clin. Oncol (1993) 11(9):1729–1736.
  • AYASH LJ, HUNT M, ANTMAN K et al: Hepatic venoocclusive disease in autologous bone marrow transplantation of solid tumors and lymphomas. J. Clia Oncol (1990) 8(10):1699–1706.
  • GILES F, GARCIA-MANERO G, CORTES J et al.: Ursodiol does not prevent hepatic venoocclusive disease associated with Mylotarg therapy. Haematologica (2002) 87(10):1114–1116.
  • ESTEY EH, THALL PF, GILES FJ et al: Gemtuzumab ozogamicin with or without interleukin 11 in patients 65 years of age or older with untreated acute myeloid leukemia and high-risk myelodysplastic syndrome: comparison with idarubicin plus continuous-infusion, high-dose cytosine arabinoside. Blood (2002) 99(12)4343–4349.
  • TSIMBERIDOU A, ESTEY E, CORTES J et al: Gemtuzumab, fludarabine, cytarabine, and cyclosporine in patients with newly diagnosed acute myelogenous leukemia or high-risk myelodysplastic syndromes. Cancer (2003) 97(6):1481–1487.
  • KELL WJ, BURNETT AK, CHOPRA R et al: A feasibility study of simultaneous administration of gemtuzumab ozogamicin with intensive chemotherapy in induction and consolidation in younger patients with acute myeloid leukemia. Blood (2003) 102(13):4277–4283.
  • •Large pilot study of gemtuzumab in combination with chemotherapy in de novo AML.
  • DE ANGELO DJ, SCHIFFER C, STONE R et al: Interim analysis of a Phase II study of the safety and efficacy of gemtuzumab ozogamicin (Mylotarg®) given in combination with cytarabine and daunorubicin in patients < 60 years old with untreated acute myeloid leukemia. Blood (2002) 100(11):198a.
  • DE ANGELO DJ, STONE RIVI, DURRANT S et al: Gemtuzumab Ozogamicin (Mylotarg®) in combination with induction chemotherapy for the treatment of patients with de novo acute myeloid leukemia: two age-specific Phase II trials. Blood(2003) 102(11):100a.
  • GRUNEWALD R, KANTARJIAN H, DU M et al.: Gemcitabine in leukemia: a Phase I clinical, plasma, and cellular pharmacology study. J. Clin. Oncol (1992) 10(3):406–413.
  • GANDHI V, PLUNKETT W: Modulatory activity of 2',2'-difluorodeoxycytidine on the phosphorylation and cytotoxicity of arabinosyl nucleosides. Cancer Res. (1990) 50(12):3675–3680.
  • SHEWACH DS, REYNOLDS KK, HERTEL L: Nucleotide specificity of human deoxycytidine kinase. Mol Pharmacol (1992) 42(3):518–524.
  • GANDHI V, PLUNKETT W, DU M, AYRES M, ESTEY EH: Prolonged infusion of gemcitabine: clinical and pharmacodynamic studies during a Phase I trial in relapsed acute myelogenous leukemia. J. Clin. Oncol (2002) 20(3):665–673.
  • RIZZIERI DA, BASS AJ, ROSNER GL et al: Phase I evaluation of prolonged-infusion gemcitabine with mitoxantrone for relapsed or refractory acute leukemia. Clin. Oncol. (2002) 20(3):674–679.
  • SJOBERG AH, WANG L, ERIKSSON S: Substrate specificity of human recombinant mitochondrial deoxyguanosine kinase with cytostatic and antiviral purine and pyrimidine analogs. Mol. Pharmacol (1998) 53(2):270–273.
  • HATZIS P, AL MADHOON AS, JULLIG M et al: The intracellular localization of deoxycytidine kinase. J. Chem. (1998) 273(46):30239–30243.
  • CARSON DA, WASSON DB, ESPARZA LM et al.: Oral antilymphocyte activity and induction of apoptosis by 2-chloro-2'-arabino-fluoro-2'-deoxyadenosine. Proc. Nati Acad. Sci. USA (1992) 89(7):2970–2974.
  • PARKER WB, SHADDIX SC, CHANG CH et al: Effects of 2-chloro 9 (2 deoxy 2 fluoro-beta-D-arabinofuranosyfladenine on K562 cellular metabolism and the inhibition of human ribonucleotide reductase and DNA polymerases by its 5'-triphosphate. Cancer Res. (1991) 51(9):2386–2394.
  • PARKER WB, SHADDIX SC, ROSE LM et al.: Comparison of the mechanism of cytotoxicity of 2-chloro 9 (2 deoxy-2-fluoro-beta-D-arabinofuranosyfladenine, 2-chloro 9 (2 deoxy-2-fluoro- beta-D-ribofuranosyl)adenine, and 2-chloro-9-(2-deoxy-2,2-difluoro- beta-D-ribofuranosyl)adenine in CEM cells. Mol. Pharmacol (1999) 55(3):515–520.
  • LINDEMALM S, LILIEMARK J, GRUBER A et al.: Comparison of cytotoxicity of 2-chloro-2'-arabino-fluoro-2'-deoxyadenosine (clofarabine) with cladribine in mononuclear cells from patients with acute myeloid and chronic lymphocytic leukemia. Haematologica (2003) 88(3):324–332.
  • KANTARJIAN H, GANDHI V, CORTES J et al: Phase II clinical and pharmacologic study of clofarabine in patients with refractory or relapsed acute leukemia. Blood (2003) 102(7):2379–2386.
  • •Exciting Phase II results with clofarabine as single agent.
  • KANTARJIAN HM, GANDHI V, KOZUCH P et al: Phase I clinical and pharmacology study of clofarabine in patients with solid and hematologic cancers. Clin. Oncol. (2003) 21(6):1167–1173.
  • CREWS KR, GANDHI V, SRIVASTAVA DK et al.: Interim comparison of a continuous infusion versus a short daily infusion of cytarabine given in combination with cladribine for pediatric acute myeloid leukemia.. Clin. Oncol. (2002) 20(20):4217–4224.
  • GANDHI V, HUANG P, CHAPMAN AJ, CHEN F, PLUNKETT W: Incorporation of fludarabine and 1-beta-D-arabinofuranosylcytosine 5'-triphosphates by DNA polymerase alpha: affinity, interaction, and consequences. Clin. Cancer Res. (1997) 3(8):1347–1355.
  • ECKER G: Troxacitabine (Shire Pharmaceuticals). Curr. Opin. Investig. Drugs (2002) 3(10):1533–1538.
  • WEITMAN S, MARTY J, JOLI VET J, LOCAS C, VON HOFF DD: The new dioxolane, ( ) 2' deoxy 3' oxacytidine (BCH-4556, troxacitabine), has activity against pancreatic human tumor xenografts. Clin. Cancer Res. (2000) 6(4):1574–1578.
  • GOURDEAU H, CLARKE ML, OUELLET F et al.: Mechanisms of uptake and resistance to troxacitabine, a novel deoxycytidine nucleoside analogue, in human leukemic and solid tumor cell lines. Cancer Res. (2001) 61(19):7217–7224.
  • GROVE KL, GUO X, LIU SH et al: Anticancer activity of beta-L-dioxolane-cytidine, a novel nucleoside analogue with the unnatural L configuration. Cancer Res. (1995) 55(14):3008–3011.
  • GROVE KL, CHENG YC: Uptake and metabolism of the new anticancer compound beta -L- ( ) dioxolane-cytidine in human prostate carcinoma DU-145 cells. Cancer Res. (1996) 56(18):4187–4191.
  • GILES FJ, CORTES JE, BAKER SD et al: Troxacitabine, a novel dioxolane nucleoside analog, has activity in patients with advanced leukemia. J. Clin. Oncol (2001) 19(3):762-771. 198.
  • GILES FJ, GARCIA-MANERO G, CORTES JE et al: Phase II study of troxacitabine, a novel dioxolane nucleoside analog, in patients with refractory leukemia. Oncol (2002) 20(3):656–664.
  • GILES F, ESTEY E, CORTES J et al.: Adaptively randomized prospective study of troxacitabine and Ara-C (A), troxacitabine and idarubicin (I), and IA in older patients with unfavorable karyotype AML. Blood (2002) 100(11):563a. zoo. GILES FJ, KANTARJIAN HM, CORTES JE et al: Adaptive randomized study of idarubicin and cytarabine versus troxacitabine and cytarabine versus troxacitabine and idarubicin in untreated patients 50 years or older with adverse karyotype acute myeloid leukemia. I Clin. Oncol (2003) 21(9):1722–1727.
  • TAYLOR SM, JONES PA: Changes in phenotypic expression in embryonic and adult cells treated with 5-azacytidine../. Physiol. (1982) 111(2):187–194.
  • SILVERMAN LR, DEMAKOS EP, PETERSON BL et al.: Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B.. Oncol (2002) 20(10):2429–2440.
  • KORNBLITH AB, HERNDON JE, SILVERMAN LR et al.: Impact of azacytidine on the quality of life of patients with myelodysplastic syndrome treated in a randomized Phase III trial: a Cancer and Leukemia Group B study. I Clin. Oncol. (2002) 20(10):2441–2452.
  • LUBBERT M, WIJERMANS P, KUNZMANN R et al: Cytogenetic responses in high-risk myelodysplastic syndrome following low-dose treatment with the DNA methylation inhibitor 5-aza-2'-deoxycytidine. BE Haematol (2001) 114(2)349–357.
  • PFEIFER GP, STEIGERWALD SD, HANSEN RS, GARTLER SM, RIGGS AD: Polymerase chain reaction-aided genomic sequencing of an X chromosome-linked CpG island: methylation patterns suggest clonal inheritance, CpG site autonomy, and an explanation of activity state stability. Proc. Nati Acad. Sci. USA (1990) 87(21):8252–8256.
  • SUZUKI H, GABRIELSON E, CHEN W et al.: A genomic screen for genes upregulated by demethylation and histone deacetylase inhibition in human colorectal cancer. Nat. Genetics (2002) 31(2):141–149.
  • 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. Genetics (1999) 21(1):103–107.
  • CHENG JC, MATSEN CB, GONZALES FA et al.: Inhibition of DNA methylation and reactivation of silenced genes by zebularine. Nati Cancer Inst. (2003) 95(5):399–409.
  • MARCUCCI G, BRUNNER RJ, BINKLEY PF et al: Phase I trial of the histone deacetylase inhibitor depsipeptide (FR901228) in acute myeloid leukemia (AML). Blood (2003) 100(11):86a.
  • KUENDGEN AM, STRUPP C, TAPPRICH C et al: Valproic acid alone or in combination with all-trans-retinoic acid (ATRA) for the treatment of myelodysplastic syndromes and sAMUMDS. Blood (2003) 102(11):428a.
  • DRESCHER B, GORLICH K, DOHRING A et al: Effect of the histone deacetylase inhibitor valproic acid alone and in combination with all-trans retinoic acid on t(15;17) positive leukemic cells. Blood (2003) 102(11):620a.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.