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Leukemia & Lymphoma Volume 44, 2003 - Issue 6
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Research Article

Prognostic Implications of the Presence of FLT3 Mutations in Patients with Acute Myeloid Leukemia

Panagiotis D. Kottaridis Department of Haematology, Royal Free and University College London Medical School, 98 Chenies Mews, London WC1E 6HX, UK
,
Rosemary E. Gale Department of Haematology, Royal Free and University College London Medical School, 98 Chenies Mews, London WC1E 6HX, UK
&
David C. Linch Department of Haematology, Royal Free and University College London Medical School, 98 Chenies Mews, London WC1E 6HX, UK
Pages 905-913 | Published online: 01 Jul 2009

  • Rees, J.K., Gray, R. G. and Wheatley, K. (1996) "Dose intensification in acute myeloid leukaemia: greater effectiveness at lower cost. Principal report of the Medical Research Council's AML9 study. MRC Leukaemia in Adults Working Party", Br. J. Haematol. 94, 89-98.
  • Burnett, A.K., Wheatley, K., Goldstone, A. H., Gibson, B., Webb, D., Prentice, A.G., Milligan, D.W.: MRC AML 12 (2002) A comparison of ADE vs MAE and S-DAT vs. H-DAT ± retinoic acid for induction and four vs five total courses using chemotherapy or stem cell transplant in consolidation, to 3459 patients under 60 years with AML. Blood. 100,155a.
  • Buchner, T., Hiddemann, W., Wormann, B., Loffler, H., Gassmann, W., Haferlach, T., Fonatsch, C., Haase, D., Schoch, C., Hossfeld, D., Lengfelder, E., Aul, C., Heyll, A., Maschmeyer, G., Ludwig, W.D., Sauerland, M.C. and Heinecke, A. (1999) "Double induction strategy for acute myeloid leukemia: the effect of highdose cytarabine with mitoxantrone instead of standard-dose cytarabine with daunorubicin and 6-thioguanine: a randomized trial by the German AML Cooperative Group", Blood 93, 4116-4124.
  • Wheatley, K., Burnett, A.K., Goldstone, A.H., Gray, R.G., Hann, I.M., Harrison, C.J., Rees, J.K., Stevens, R.F. and Walker, H. (1999) "A simple, robust, validated and highly predictive index for the determination of risk-directed therapy in acute myeloid leukaemia derived from the MRC AML 10 trial. United Kingdom Medical Research Council's Adult and Childhood Leukaemia Working Parties", Br. J. Haematol. 107, 69-79.
  • Grimwade, D., Walker, H., Oliver, R. Wheatley, K., Harrison, C. Harrison, G., Rees, J., Kann, J., Stevens, R., Burnert, A. and Goldstone, A. (1998) "The importance of diagnostic cytogenetics on outcome in AML: analysis of 1.612 patients entered into the MRC AML 10 trial. The Medical Research Council Adult and Children's Leukaemia Working Parties", Blood 92, 2322-2333.
  • Slovak, M.L., Kopecky, K.J., Cassileth, P.A., Harrington, D.H., Theil, K.S., Mohamed, A., Paietta, E., Willman, C.L., Head, D.R., Rowe, J.M., Forman, S.J. and Appelbaum, FR. (2000) "Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group Study", Blood 96, 4075-4083.
  • Burnett, A.K. (2002) "Current controversies: which patients with acute myeloid leukaemia should receive a bone morrow transplantation?-an adult trealer's view", Br. J. Haematol. 118, 357-364.
  • Alexander, W.S. and Nicola, N.A. (1998) "Hemopoietic growth factor receptor abnormalities in leukemia", Leuk. Res. 22, 1097-1111.
  • Nakao, M., Yokota, S., Iwai, T., Kaneko, H., Horiike, S., Kashima, K., Sonoda, Y., Fujimoto, T. and Misawa, S. (1996) "Internal tandem duplication of the flt3 gene found in acute myeloid leukemia", Leukemia 10, 1911-1918.
  • Shurin, M.R., Esche, C. and Lotze, M.T. (1998) "FLT3: receptor and ligand. Biology and potential clinical application", Cytokine Growth Factor Rev 9, 37-48. Review.
  • Agnes, F. Shamoon, B., Dina, C., Rosnet, O., Birnbaum, D. and Galibert, F. (1994) "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 145, 283-288.
  • Rosnet, O., Mattei, M.G., Marchetto, S. and Birnbaum, D. (1991) "Isolation and chromosomal localization of a novel FMS-like tyrosine kinase gene", Genomics 9, 380-385.
  • Abu-Duhier, F.M., Goodeve, A.C., Wilson, G.A., Care, R.S., Peake, I.R. and Reilly, J.T. (2001) "Genomic structure of human FLT3: implications for mutational analysis", Br. J. Haematol. 113, 1076-1077.
  • Drexler, H.G. (1996) "Expression of FLT3 receptor and response to FLT3 ligand by leukemic cells", Leukemia 10, 588-599.
  • Yokota, S., Kiyoi, H., Nakao, M., Iwai, T., Misawa, S., Okuda, T., Sonoda, Y., Abe, T., Kabsima, K., Matsuo, Y. and Naoe, T. (1997) "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 11, 1605-1609.
  • Horiike, S., Yokota, S., Nakao, M., Iwai, T., Sasai, Y, Kaneko, H., Taniwaki, M., Kashima, K., Fujii, H., Abe, T. and Misawa, S. (1997) "Tandem duplications of the FLT3 receptor gene are associated with leukemic transformation of myelodysplasia", Leukemia 11, 1442-1446.
  • Kiyoi, H., Naoe, T., Yokota, S., Nakao, M., Minami, S., Kuriyama, K., Takeshita, A., Saito, K., Hasegawa, S., Shimodaira, S., Tamura, J., Shimazaki, C., Matsue, K., Kobayashi, H., Arima, N., Suzuki, R., Morishita, H., Saito, H., Ueda, R. and Ohno, R. (1997) "Internal tandem duplication of FLT3 associated with leukocytosis in acute promyelocytic leukemia. Leukemia Study Group of the Ministry of Health and Welfare (Kohseisho)", Leukemia 11, 1447 1452.
  • Iwai, T., Yokota, S., Nakao, M., Okamoto, T. Taniwaki, M., Onodera, N., Watanabe, A., Kikuta, A., Tanaka, A., Asami, K., Sekine, I., Mugishima, H., Nishimura, Y., Koizumi, S., Horikoshi, Y., Mimaya, J., Ohta, S., Nishikawa, K., Iwai, A., Shimokawa, T., Nakayama, M., Kawakami, K., Gushiken, T., Hyakuna, N., Fujimoto, T., et al. (1999) "Internal tandem duplication of the FLT3 gene and clinical evaluation in childhood acute myeloid leukemia. The Children's Cancer and Leukemia Study Group. Japan", Leukemia 13, 38-43.
  • Xu, F., Taki, T., Yang, H.W., Hanada R., Hoogo, T., Ohnishi, H., Kobayashi, M., Bessho, F., Yanagisawa, M. and Hayashi, Y. (1999) "Tandem duplication of the FLT3 gene is found in acute lymphoblastic leukaemia as well as acute myeloid leukaemia but not in myelodysplastic syndrome or juvenile chronic myelogenous leukaemia in children", Br. J. Haematol. 105, 155-162.
  • Kiyoi, H., Towatari, M., Yokota, S., Hamaguchi, M., Ohno, R., Saito, H. and Naoe, T. (1998) "Internal tandem duplication of the FLT3 gene is a novel modality of elongation mutation which causes constitutive activation of the product", Leukemia 12, 1333-1337.
  • Hayakawa, F., Towatari, M., Kiyoi, H., Tanimoto, M., Kitamura, T., Saito, H. and Naoe, T. (2000) "Tandem-duplicated Flt3 constitutively activates STATS and MAP kinase and introduces autonomous cell growth in IL-3-dependent cell lines", Oncogene 19, 624-631.
  • Tse, K.F., Mukherjee, G. and Small, D. (2000) "Constitutive activation of FLT3 stimulates multiple intracellular signal transducers and result:» in transformation", Leukemia 14, 1766-1776.
  • Mizuki, M., Fenski, R., Halfter, H., Matsumura, I., Schmidt, R., Muller, C., Gruning, W., Kratz-Albers, K., Serve, S., Steur, C., Buchner, T., Kienast, J., Kanakura, Y. Berdel, W.E. and Serve, H. (2000) "Flt3 mutations from patients with acute myeloid leukemia induce transformation of 32D cells mediated by the Ras and STAT5 pathways", Blood 96, 3907-3914.
  • Kelly, L.M., Liu, Q., Kutok, J.L., Williams, I.R., Boulton, C.L. and Gilliland, D.G. (2002) "FLT3 internal tandem duplication mutations associated with human acute myeloid leukemias induce myeloproliferative disease in a murine bone marrow transplant model", Blood 99, 310-318.
  • Yamamoto, Y., Kiyoi, H., Nakano, Y., Suzuki, R., Kodera, Y. Miyawaki, S., Asou, N., Kuriyama, K., Yagasaki, F., Shimazaki, C., Akiyama, H., Saito, K., Nishimura, M., Motoji, T., Shinagawa, K., Takeshita, A., Saito, H., Ueda, R., Ohno, R. and Naoe, T. (2001) "Activating mutation of D835 within the activation loop of FLT3 in human hematologic malignancies", Blood 97, 2434-2439.
  • Abu-Duhier, F.M., Goodeve, A.C., Wilson, G.A., Care, R.S., Peake, I.R. and Reilly, J.T. (2001) "Identification of novel FLT-3 Asp835 mutations in adult acute myeloid leukaemia", Br. J. Haematol. 113, 983- 988.
  • Spiekermann, K., Bagrintseva, K., Schoch, C., Haferlach, T., Hiddemann, W. and Schnittger, S. (2002) "A new and recurrent activating length mutation in exon 20 of the FLT3 gene in acute myeloid leukemia", Blood 100, 3423-3425.
  • Stirewalt, D.L., Kopecky, K.J., Meshinchi, S., Appelbaum, F.R., Slovak, M.L., Willman, C.L. and Radich, J.P. (2001) "FLT3, RAS, and TP53 mutations in elderly patients with acute myeloid leukemia", Blood 97, 3589-3595.
  • Kondo, M., Horibe, K., Takahashi, Y., Matsumoto, K., Fukuda, M., Inaba, J., Kato, K., Kojima, S. and Matsuyama, T. (1999) "Prognostic value of internal tandem duplication of the FLT3 gene in childhood acute myelogenous leukemia", Med. Pediatr. Oncol., 33, 525-529.
  • Xu, F., Taki, T., Eguchi, M., Kamada, N., Ishii, E., Endo, M. and Hayashi, Y. (2000) 'Tandem duplication of the FLT3 gene is infrequent in infant acute leukemia. Japan Infant Leukemia Study Group [letter]", Leukemia 14, 945-947.
  • Meshinchi, S., Woods, W.G., Stirewalt, D.L., Sweetser, D.A., Buckley, J.D., Tjoa, T.K., Bernstein, I.D. and Radich, J.P. (2001) "Prevalence and prognostic significance of Flt3 internal tandem duplication in pediatric acute myeloid leukemia", Blood 97, 89 94.
  • Liang, D.C., Shih, L.Y, Hung, I.J., Yang, C.P., Chen, S.H., Jaing, T.H., Liu, H.C. and Chang, W.H. (2002) "Clinical relevance of internal tandem duplication of the FLT3 gene in childhood acute myeloid leukemia", Cancer 94, 3292-3298.
  • Thiede, C., Steudel, C., Mohr, B., Scbaich, M., Schakel, L., Platzbecker, U., Wermke, M., Bornhauser, M., Ritter, M., Neubauer, A., Ehninger, G. and Illmer, T. (2002) "Analysis of FLT3-activating mutations in 979 patients with acute myelogenous leukemia: association with FAB subtypes and identification of subgroups with poor prognosis", Blood 99, 4326-4335.
  • Kottaridis, P.D., Gale, R.E., Frew, M.E., Harrison, G., Langabeer, S.E., Belton, A.A., Walker, H., Wheatley, K., Bowen, D.T., Burnett, A.K., Goldstone, A.H. and Linch, D.C. (2001) "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 98, 1752-1759.
  • Kiyoi, H., Naoe, T., Nakano, Y. Yukota, S., Minami, S., Miyawaki, S., Asou, N., Kuriyama, K., Jinnai, I., Shimazaki, C., Akiyama, H., Saito, K., Oh, H., Motoji, T., Ornoto, E., Saito, H., Ohno, R. and L'eda, R. (1999) "Prognostic implication of FLT3 and N-RAS gene mutations in acute myeloid leukemia", Blood 93, 3074-3080.
  • Schnittger, S., Schoch, C., Dugas, M., Kern, W., Staib, P., Wuchter, C., Loffler, H., Sauerland, C.M., Serve, H., Buchner, T., Haferlach, T. and Hiddemann, W. (2002) "Analysis of FLT3 length mutations in 1003 patients with acute myeloid leukemia: correlation to cytogenetics, FAB subtype, and prognosis in the AMLCG study and usefulness as a marker for the detection of minimal residual disease", Blood 100, 59-66.
  • Ferrant, A. Doyen, C., Delannoy, A., Straetrnans, N., Martial, P., Mineur, P., Bosly, A., Van den Berghe, H. and Michaux, J.L. (1995) "Karyotype in acute mycloblastic leukemia: prognostic significance in a prospective study assessing bone marrow transplantation in first remission", Bone Marrow Transplant. 15, 685-690.
  • Gale, R.P., Horowitz, M.M., Weiner, R.S., Ash, R.C., Atkinson, K., Babu, R., Dicke, K.A., Klein, J.P., Lowenberg, B., Reiffers, J., et al. (1995) "Impact of cytogenetic abnormalities on outcome of bone marrow transplants in acute myclogonous leukemia in first remission", Bone Marrow Transplant 16, 203-208.
  • Rombouts, W.J., Blokland, I., Lowenberg, B. and Ploemacher, R.E. (2000) "Biological characteristics and prognosis of adult acute myeloid leukemia with internal tandem duplications in the Flt3 gene", Leukemia 14, 675-683.
  • Whitman, S.P., Archer, K.J., Feng, L., Baldus, C., Becknell, B., Carlson, B.D., Carroll, A.J., Mrozek, K., Vardiman, J.W., George, S.L., Kolitz, I.E., Larson, R.A., Bloomfield, C.D. and Caligiuri, M.A. (2001) "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. 61, 7233-7239.
  • Abu-Duhier, F.M., Goodeve, A.C., Wilson, G.A., Gari, M.A., Peake, I.R., Rees, D.C., Vandenberghe, E.A., Winship, P.R. and Reilly, J.T. (2000) "FLT3 internal tandem duplication mutations in adult acute myeloid leukaemia define a high-risk group", Br. J. Haematol. 111, 190-195.
  • Lowenberg, B. (2001) "Managing therapy in older adult patients with acute myeloid leukemia", Semin. Hematol. 38, 10-16.
  • Dann, E.J. and Rowe, J.M. (2001) "Biology and therapy of secondary leukaemias", Best Pract. Res. Clin. Haematol. 14, 119-137.
  • Miller, K.B. (2000) "Myelodysplastic syndromes", Curr. Treat. Options Oncol. 1, 63-69.
  • Olney, H.J. and Le Beau, M.M. (2001) "The cytogenetics of myelodysplastic syndromes", Best Pract. Res. Clin. Haematol. 14, 479- 495.
  • Boissel, N., Cayuela, J.M., Preudhomme, C., Thomas, X., Grardel, N., Fund, X., Tigaud, I., Raffoux, E., Rousselot, P., Sigaux, R. Degos, L., Castaigne, S., Fenaux, P. and Dombret, H. (2002) "Prognostic significance of FLT3 internal tandem repeat in patients with de novo acute myeloid leukemia treated with reinforced courses of chemotherapy", Leukemia 16, 1699-1704.
  • Frohling, S., Breitruck, J., Schlenk, R., Kreitmeier, S., Tobis, K., Dohner, H. and Dohner, K. (2001) "FLT3 internal tandem duplications and survival in adult acute myeloid leukemia; Analysis of 188 intensively treated patients", Blood 98, 717a.
  • Nakano, Y., Kiyoi, H., Miyawaki, S., Asou, N., Ohno, R., Saito, H. and Naoe, T. (1999) "Molecular evolution of acute myeloid leukaemia in relapse: unstable N-ras and FLT3 genes compared with p53 gene", Br. J. Haematol. 104, 659-664.
  • Kottaridis, P.D., Gale, R.E., Langabeer, S.K., Frew, M.E., Bowen, D.T. and Linch, D.C. (2002) "Studies of FLT3 mutations in paired presentation and relapse samples from patients with acute myeloid leukemia: implications for the role of FLT3 mutations in leukemogenesis, minimal residual disease detection, and possible therapy with FLT3 inhibitors", Blood 100, 2393-2398.
  • Shih, L.Y., Huang, C.F., Wu, J.H., Lin, T.L., Dunn, P., Wang, P.N., Kuo, M.C., Lai, C.L. and Hsu, H.C. (2002) "Internal tandem duplication of FLT3 in relapsed acute myeloid leukemia: a comparative analysis of bone marrow samples from 108 adult patients at diagnosis and relapse", Blood 100, 2387-2392.
  • Tse, K.F., Novelli, E., Civin, C.I., Bohmer F.D. and Small D. (2001) "Inhibition of FLT3-mediatcd transformation by use of a tyrosine kinase inhibitor", Leukemia 15, 1001-1010.
  • Zhao, M., Kiyoi, H., Yamamoto, Y., Ito, M., Towalari, M., Ornura, S., Kitamura, T., Ueda, R., Saito, H. and Naoe, T. (2000) "In vivo treatment of mutant FLT3-transformed murine leukemia with a tyrosine kinase inhibitor", Leukemia 14, 374-378.
  • Levis, M., Tse, K.F., Smith, B.D., Garrett, E. and Small, D. (2001) "A FLT3 tyrosine kinase inhibitor is selectively cytotoxic to acute myeloid leukemia blasts harboring FLT3 internal tandem duplication mutations", Blood 98, 885-887.
  • Levis, M., Allebach, J., Tse, K.F., Zheng, R., Baldwin, B.R., Smith, B.D., Jones-Bolin, S., Ruggeri, B., Dionne, C. and Small, D. (2002) "A FLT3-targeted tyrosine kinase inhibitor is cytotoxic to leukemia cells in vitro and in vivo", Blood 99, 3885-3891.

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