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Flt3 in acute myelogenous leukemia

Biology, prognosis, and therapeutic implications

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Abstract

Flt3 is a tyrosine kinase receptor expressed on hematopoietic cells. Activating mutations of this receptor are encountered in over one-fourth of acute myelogenous leukemia (AML) cases and activate multiple intracellular pathways leading to cell proliferation, inhibition of apoptosis, and blockage of differentiation in leukemic blasts. AML with flt3 mutations has a worse prognosis than AML with normal flt3, at least in younger patients. Sevaral flt3 inhibitors are in various stages of preclinical and clinical development and it is hoped that specific therapies against AML with flt3 mutations will soon be available to the clinician.

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References

  1. Gilliland, D.G. and Griffin, J.D. (2002). The roles of FLT3 in hematopoiesis and leukemia. Blood 100:1532–1542.

    Article  PubMed  CAS  Google Scholar 

  2. Kiyoi, H. and Naoe, T. (2002). FLT3 in human hematologic malignancies. Leuk. Lymphoma 43:1541–1547.

    Article  PubMed  CAS  Google Scholar 

  3. Testa, U., et al. (2002). Human acute stem cell leukemia with multilineage differentiation potential via cascade activation of growth factor receptors. Blood 99:4634–4637.

    Article  PubMed  CAS  Google Scholar 

  4. Tse, K.F., Mukherjee, G. and Small, D. (2000). Constitutive activation of FLT3 stimulates multiple intracellular signal transducers and results in transformation. Leukemia 14:1766–1776.

    Article  PubMed  CAS  Google Scholar 

  5. Matthews, W., Jordan, C.T., Wiegand, G.W., Pardoll, D. and Lemischka, I.R. (1991). A receptor tyrosine kinase specific to hematopoietic stem and progenitor cell-enriched populations. Cell 65:1143–1152.

    Article  PubMed  CAS  Google Scholar 

  6. Rosnet, O., Marchetto, S., deLapeyriere, O., and Birnbaum, D. (1991). Murine Flt3, a gene encoding a novel tyrosine kinase receptor of the PDGFR/CSF1R family. Oncogene 6:1641–1650.

    PubMed  CAS  Google Scholar 

  7. Lyman, S.D., et al. (1993). Characterization of the protein encoded by the flt3 (flk2) receptor-like tyrosine kinase gene. Oncogene 8:815–822.

    PubMed  CAS  Google Scholar 

  8. Abu-Duhier, F.M., et al. (2001). Genomic structure of human FLT3: implications for mutational analysis. Br. J. Haematol. 113:1076–1077.

    Article  PubMed  CAS  Google Scholar 

  9. Lyman, S.D. and Jacobsen, S.E. (1998). c-kit ligand and Flt3 ligand: stem/progenitor cell factors with overlapping yet distinct activities. Blood 91:1101–1134.

    PubMed  CAS  Google Scholar 

  10. Christensen, J.L. and Weissman, I.L. (2001). Flk-2 is a marker in hematopoietic stem cell differentiation: a simple method to isolate long-term stem cells. Proc. Natl. Acad. Sci. USA 98:14,541–14,546.

    CAS  Google Scholar 

  11. Ebihara, Y., et al. (2002). Reconstitution of human haematopoiesis in non-obese diabetic/severe combined immunodeficient mice by clonal cells expanded from single CD34+. Br. J. Haematol. 119:525–534.

    Article  PubMed  Google Scholar 

  12. Fichelson, S. (1998). The FLT3/FLK2 ligand: structure, functions and prospects. Eur. Cytokine Netw. 9:7–22.

    PubMed  CAS  Google Scholar 

  13. Lavagna-Sevenier, C., Marchetto, S., Birnbaum, D. and Rosnet, O. (1998). FLT3 signaling in hematopoietic cells involves CBL, SHC and an unknown P115 as prominent tyrosine-phosphorylated substrates. Leukemia 12:301–310.

    Article  PubMed  CAS  Google Scholar 

  14. Scheijen, B. and Griffin, J.D. (2002). Tyrosine kinase oncogenes in normal hematopoiesis and hematological disease. Oncogene 21:3314–3333.

    Article  PubMed  CAS  Google Scholar 

  15. Mizuki, M., et al. (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.

    PubMed  CAS  Google Scholar 

  16. Kerkhoff, E. and Rapp, U.R. (1998). Cell cycle targets of Ras/Raf signalling. Oncogene 17:1457–1462.

    Article  PubMed  CAS  Google Scholar 

  17. Reuther, G.W. and Der, C.J. (2000). The Ras branch of small GTPases: Ras family members don’t fall far from the tree. Curr. Opin. Cell Biol. 12:157–165.

    Article  PubMed  CAS  Google Scholar 

  18. Vivanco, I. and Sawyers, C.L. (2002). The phosphatidylinositol 3-kinase AKT pathway in human cancer. Nature Rev. Cancer 2:489–501.

    Article  CAS  Google Scholar 

  19. Cardone, M.H., et al. (1998). Regulation of cell death protease caspase-9 by phosphorylation. Science 282:1318–1321.

    Article  PubMed  CAS  Google Scholar 

  20. Zhang, S., et al. (2000). Essential role of signal transducer and activator of transcription (Stat)5a but not Stat5b for Flt3-dependent signaling. J. Exp. Med. 192:719–728.

    Article  PubMed  CAS  Google Scholar 

  21. Rane, S.G. and Reddy, E.P. (2002). JAKs, STATs and Src kinases in hematopoiesis. Oncogene 21:3334–3358.

    Article  PubMed  CAS  Google Scholar 

  22. Birkenkamp, K.U., Geugien, M., Lemmink, H.H., Kruijer, W. and Vellenga, E. (2001) Regulation of constitutive STAT5 phosphorylation in acute myeloid leukemia blasts. Leukemia 15:1923–1931.

    PubMed  CAS  Google Scholar 

  23. Marchetto, S., et al. (1999). SHC and SHIP phosphorylation and interaction in response to activation of the FLT3 receptor. Leukemia 13:1374–1382.

    Article  PubMed  CAS  Google Scholar 

  24. Mizuki, M., et al. (2003). Suppression of myeloid transcription factors and induction of STAT response genes by AML-specific Flt3 mutations. Blood, 101:3164–3173.

    Article  PubMed  CAS  Google Scholar 

  25. Chen, X.P., et al. (2002). Pim serine/threonine kinases regulate the stability of Socs-1 protein. Proc. Natl. Acad. Sci. USA 99:2175–2180.

    Article  PubMed  CAS  Google Scholar 

  26. Allen, J.D., Verhoeven, E., Domen, J., van der Valk, M. and Berns, A. (1997). Pim-2 transgene induces lymphoid tumors, exhibiting potent synergy with c-myc. Oncogene 15:1133–1141.

    Article  PubMed  CAS  Google Scholar 

  27. Wolf, I. and Rohrschneider, L.R. (1999). Fiz1, a novel zinc finger protein interacting with the receptor tyrosine kinase Flt3. J. Biol. Chem. 274:21,478–21,484.

    CAS  Google Scholar 

  28. Serve, H., Flesch, K., Serve, S., Fenski, R. and Berdel, W.E. (1999). Expression and function of Flt3/flk2 in human tumor cell lines. Int. J. Oncol. 14:765–770.

    PubMed  CAS  Google Scholar 

  29. Drexler, H.G. (1996). Expression of FLT3 receptor and response to FLT3 ligand by leukemic cells. Leukemia 10:588–599.

    PubMed  CAS  Google Scholar 

  30. Stacchini, A., et al. (1996). Expression of type III receptor tyrosine kinases FLT3 and KIT and responses to their ligands by acute myeloid leukemia blasts. Leukemia 10:1584–1591.

    PubMed  CAS  Google Scholar 

  31. Turner, A.M., Lin, N.L., Issarachai, S., Lyman, S.D. and Broudy, V.C. (1996). FLT3 receptor expression on the surface of normal and malignant human hematopoietic cells. Blood 88:3383–3390.

    PubMed  CAS  Google Scholar 

  32. Lisovsky, M., et al. (1996). Flt3 ligand stimulates proliferation and inhibits apoptosis of acute myeloid leukemia cells: regulation of Bcl-2 and Bax. Blood 88:3987–3997.

    PubMed  CAS  Google Scholar 

  33. Nakao, M.J., Janssen, W., Erz, D., Seriu, T. and Bartram C.R. (2000). Tandem duplication of the FLT3 gene in acute lymphoblastic leukemia: a marker for the monitoring of minimal residual disease. Leukemia 14:522–524.

    Article  PubMed  CAS  Google Scholar 

  34. Yokota, S., et al. (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.

    Article  PubMed  CAS  Google Scholar 

  35. Horiike, S., et al. (1997). Tandem duplications of the FLT3 receptor gene are associated with leukemic transformation of myelodysplasia. Leukemia 11:1442–1446.

    Article  PubMed  CAS  Google Scholar 

  36. Nakao, M., et al. (1996). Internal tandem duplication of the flt3 gene found in acute myeloid leukemia. Leukemia 10:1911–1918.

    PubMed  CAS  Google Scholar 

  37. Kottaridis, P.D., et al. (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.

    Article  PubMed  CAS  Google Scholar 

  38. Kiyoi, H., Ohno, R., Ueda, R., Saito, H. and Naoe, T. (2002). Mechanism of constitutive activation of FLT3 with internal tandem duplication in the juxtamembrane domain. Oncogene 21:2555–2563.

    Article  PubMed  CAS  Google Scholar 

  39. Hayakawa, F., et al. (2000). Tandem-duplicated Flt3 constitutively activates STAT5 and MAP kinase and introduces autonomous cell growth in IL-3-dependent cell lines. Oncogene 19:624–631.

    Article  PubMed  CAS  Google Scholar 

  40. Kiyoi, H., et al. (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.

    Article  PubMed  CAS  Google Scholar 

  41. Zheng, R., Friedman, A.D. and Small, D. (2002). Targeted inhibition of FLT3 overcomes the block to myeloid differentiation in 32Dcl3 cells caused by expression of FLT3/ITD mutations. Blood 100:4154–4161.

    Article  PubMed  CAS  Google Scholar 

  42. Abu-Duhier, F.M., et al. (2001). Identification of novel FLT-3 Asp835 mutations in adult acute myeloid leukaemia. Br. J. Haematol. 113:983–988.

    Article  PubMed  CAS  Google Scholar 

  43. Thiede, C., et al. (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.

    Article  PubMed  CAS  Google Scholar 

  44. Yamamoto, Y., et al. (2001). Activating mutation of D835 within the activation loop of FLT3 in human hematologic malignancies. Blood 97:2434–2439.

    Article  PubMed  CAS  Google Scholar 

  45. Griffin, J.D. (2001). Point mutations in the FLT3 gene in AML. Blood 97:2193.

    Article  CAS  Google Scholar 

  46. Spiekermann, K., et al. (2002). A new and recurrent activating length mutation in exon 20 of the FLT3 gene in acute myeloid leukemia. Blood 100:3423–3425.

    Article  PubMed  CAS  Google Scholar 

  47. Fenski, R., et al. (2000). Constitutive activation of FLT3 in acute myeloid leukaemia and its consequences for growth of 32D cells. Br. J. Haematol. 108:322–330.

    Article  PubMed  CAS  Google Scholar 

  48. Kelly, L.M., et al. (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.

    Article  PubMed  CAS  Google Scholar 

  49. Kelly, L.M., et al. (2002). PML/RARalpha and FLT3-ITD induce an APL-like disease in a mouse model. Proc. Natl. Acad. Sci. USA 99:8283–8288.

    Article  PubMed  CAS  Google Scholar 

  50. Kottaridis, P.D., et al. (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.

    Article  PubMed  CAS  Google Scholar 

  51. Kiyoi, H., et al. (1999). Prognostic implication of FLT3 and N-RAS gene mutations in acute myeloid leukemia. Blood 93:3074–3080.

    PubMed  CAS  Google Scholar 

  52. Kondo, M., et al. (1999). Prognostic value of internal tandem duplication of the FLT3 gene in childhood acute myelogenous leukemia. Med. Pediatr. Oncol. 33:525–529.

    Article  PubMed  CAS  Google Scholar 

  53. Liang, D.C., et al. (2002). Clinical relevance of internal tandem duplication of the FLT3 gene in childhood acute myeloid leukemia. Cancer 94:3292–3298.

    Article  PubMed  CAS  Google Scholar 

  54. Meshinchi, S., et al. (2001). Prevalence and prognostic significance of Flt3 internal tandem duplication in pediatric acute myeloid leukemia. Blood 97:89–94.

    Article  PubMed  CAS  Google Scholar 

  55. Schnittger, S., et al. (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.

    Article  PubMed  CAS  Google Scholar 

  56. Rowe, J.M. (2000). Treatment of acute myelogenous leukemia in older adults. Leukemia 14:480–487.

    Article  PubMed  CAS  Google Scholar 

  57. Inokuchi, K., et al. (2002). Loss of DCC gene expression is of prognostic importance in acute myelogenous leukemia. Clin. Cancer Res. 8:1882–1888.

    PubMed  CAS  Google Scholar 

  58. 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.

    Article  PubMed  CAS  Google Scholar 

  59. Abu-Duhier, F.M., et al. (2000). FLT3 internal tandem duplication mutations in adult acute myeloid leukaemia define a high-risk group. Br. J. Haematol. 111:190–195.

    Article  PubMed  CAS  Google Scholar 

  60. Stirewalt, D.L., et al. (2001). FLT3, RAS, and TP53 mutations in elderly patients with acute myeloid leukemia. Blood 97:3589–3595.

    Article  PubMed  CAS  Google Scholar 

  61. Whitman, S.P., et al. (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.

    PubMed  CAS  Google Scholar 

  62. Boissel, N., et al. (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.

    Article  PubMed  CAS  Google Scholar 

  63. Preudhomme, C., et al. (2002). Favorable prognostic significance of CEBPA mutations in patients with de novo acute myeloid leukemia: a study from the Acute Leukemia French Association (ALFA). Blood 100:2717–2723.

    Article  PubMed  CAS  Google Scholar 

  64. Iwai, 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.

    Article  PubMed  CAS  Google Scholar 

  65. Arrigoni, P., et al. (2003). FLT3 internal tandem duplication in childhood acute myeloid leukemia: association with hyperleukocytosis in acute promyelocytic leukemia. Br. J. Haematol. 120:89–92.

    Article  PubMed  CAS  Google Scholar 

  66. Asou, N., et al. (2001). Analysis of prognostic factors in newly diagnosed patients with acute promyelocytic leukemia: the APL92 study of the Japan Adult Leukemia Study Group (JALSG). Cancer Chemother. Pharmacol. 48(Suppl. 1):S65-S71.

    Article  PubMed  Google Scholar 

  67. Hochhaus, A., et al. (2000). Detection and quantification of residual disease in chronic myelogenous leukemia. Leukemia 14:998–1005.

    Article  PubMed  CAS  Google Scholar 

  68. Serrano, J., et al. (2000). Molecular analysis of lineage-specific chimerism and minimal residual disease by RTPCR of p210(BCR-ABL) and p190(BCR-ABL) after allogeneic bone marrow transplantation for chronic myeloid leukemia: increasing mixed myeloid chimerism and p190(BCR-ABL) detection precede cytogenetic relapse. Blood 95:2659–2665.

    PubMed  CAS  Google Scholar 

  69. Stirewalt, D.L., Willman, C.L. and Radich, J.P. (2001). Quantitative, real-time polymerase chain reactions for FLT3 internal tandem duplications are highly sensitive and specific. Leuk. Res. 25:1085–1088.

    Article  PubMed  CAS  Google Scholar 

  70. Shih, L.Y., et al. (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.

    Article  PubMed  CAS  Google Scholar 

  71. Hovland, R., Gjertsen, B.T. and Bruserud, O. (2002). Acute myelogenous leukemia with internal tandem duplication of the Flt3 gene appearing or altering at the time of relapse: a report of two cases. Leuk. Lymphoma 43:2027–2029.

    Article  PubMed  CAS  Google Scholar 

  72. Nakano, Y., et al. (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.

    Article  PubMed  CAS  Google Scholar 

  73. Gilliland, D.G. (2002). Murky waters for MRD detection in AML: flighty FLT3/ITDs. Blood 100:2277.

    Article  CAS  Google Scholar 

  74. Okada, H., et al. (1998). AML1(-/-) embryos do not express certain hematopoiesis-related gene transcripts including those of the PU.1 gene. Oncogene 17:2287–2293.

    Article  PubMed  CAS  Google Scholar 

  75. Frohling, S., et al. (2002). Prognostic significance of activating FLT3 mutations in younger adults (16 to 60 years) with acute myeloid leukemia and normal cytogenetics: a study of the AML Study Group Ulm (AMLSG ULM). Blood 100:4372–4380.

    Article  PubMed  CAS  Google Scholar 

  76. Sawyers, C.L. (2002). Finding the next Gleevec: FLT3 targeted kinase inhibitor therapy for acute myeloid leukemia. Cancer Cell 1:413–415.

    Article  PubMed  CAS  Google Scholar 

  77. Propper, D.J., et al. (2001). Phase I and pharmacokinetic study of PKC412, an inhibitor of protein kinase C. J. Clin. Oncol. 19:1485–1492.

    PubMed  CAS  Google Scholar 

  78. Weisberg, E., et al. (2002). Inhibition of mutant FLT3 receptors in leukemia cells by the small molecule tyrosine kinase inhibitor PKC412. Cancer Cell 1:433–443.

    Article  PubMed  CAS  Google Scholar 

  79. Yee, K.W., et al. (2002). SU5416 and SU5614 inhibit kinase activity of wild-type and mutant FLT3 receptor tyrosine kinase. Blood 100:2941–2949.

    Article  PubMed  CAS  Google Scholar 

  80. Spiekermann, K., et al. (2003). The protein tyrosine kinase inhibitor SU5614 inhibits FLT3 and induces growth arrest and apoptosis in AML-derived cell lines expressing a constitutively activated FLT3. Blood, 101:1494–1504.

    Article  PubMed  CAS  Google Scholar 

  81. Smolich, B.D., et al. (2001). The antiangiogenic protein kinase inhibitors SU5416 and SU6668 inhibit the SCF receptor (c-kit) in a human myeloid leukemia cell line and in acute myeloid leukemia blasts. Blood 97:1413–1421.

    Article  PubMed  CAS  Google Scholar 

  82. Stopeck, A., et al. (2002). Results of a phase I dose-escalating study of the antiangiogenic agent, SU5416, in patients with advanced malignancies. Clin. Cancer Res. 8:2798–2805.

    PubMed  CAS  Google Scholar 

  83. Mesters, R.M., et al. (2001). Stable remission after administration of the receptor tyrosine kinase inhibitor SU5416 in a patient with refractory acute myeloid leukemia. Blood 98:241–243.

    Article  PubMed  CAS  Google Scholar 

  84. Levis, M., et al. (2002). A FLT3-targeted tyrosine kinase inhibitor is cytotoxic to leukemia cells in vitro and in vivo. Blood 99:3885–3891.

    Article  PubMed  CAS  Google Scholar 

  85. Kelly, L.M., et al. (2002). CT53518, a novel selective FLT3 antagonist for the treatment of acute myelogenous leukemia (AML). Cancer Cell 1:421–432.

    Article  PubMed  CAS  Google Scholar 

  86. 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.

    Article  PubMed  CAS  Google Scholar 

  87. Teller, S., et al. (2002). Bis(1H-2-indolyl)-1-methanones as inhibitors of the hematopoietic tyrosine kinase Flt3. Leukemia 16:1528–1534.

    Article  PubMed  CAS  Google Scholar 

  88. Tse, K.F., et al. (2002). Inhibition of the transforming activity of FLT3 internal tandem duplication mutants from AML patients by a tyrosine kinase inhibitor. Leukemia 16:2027–2036.

    Article  PubMed  CAS  Google Scholar 

  89. Minami, Y., et al. (2002). Selective apoptosis of tandemly duplicated FLT3-transformed leukemia cells by Hsp90 inhibitors. Leukemia 16:1535–1540.

    Article  PubMed  CAS  Google Scholar 

  90. Naoe, T., et al. (2001). FLT3 tyrosine kinase as a target molecule for selective antileukemia therapy. Cancer Chemother. Pharmacol. 48(Suppl. 1):S27-S30.

    Article  PubMed  CAS  Google Scholar 

  91. Zhao, M., et al. (2000). In vivo treatment of mutant FLT3-transformed murine leukemia with a tyrosine kinase inhibitor. Leukemia 14:374–378.

    Article  PubMed  CAS  Google Scholar 

  92. Mackarehtschian, K., et al. (1995). Targeted disruption of the flk2/flt3 gene leads to deficiencies in primitive hematopoietic progenitors. Immunity 3:147–161.

    Article  PubMed  CAS  Google Scholar 

  93. Shaw, S.G., Maung, A.A., Steptoe, R.J., Thomson, A.W. and Vujanovic, N.L. (1998). Expansion of functional NK cells in multiple tissue compartments of mice treated with Flt3-ligand: implications for anti-cancer and anti-viral therapy. J. Immunol. 161:2817–2824.

    PubMed  CAS  Google Scholar 

  94. Chen, K., et al. (1997). Antitumor activity and immunotherapeutic properties of Flt3-ligand in a murine breast cancer model. Cancer Res. 57:3511–3516.

    PubMed  CAS  Google Scholar 

  95. Lynch, D.H., et al. (1997). Flt3 ligand induces tumor regression and antitumor immune responses in vivo. Nature Med. 3:625–631.

    Article  PubMed  CAS  Google Scholar 

  96. Wang, A., Braun, S.E., Sonpavde, G. and Cornetta, K. (2000). Antileukemic activity of Flt3 ligand in murine leukemia. Cancer Res. 60:1895–1900.

    PubMed  CAS  Google Scholar 

  97. Costello, R.T., et al. (2002). Defective expression and function of natural killer cell-triggering receptors in patients with acute myeloid leukemia. Blood 99:3661–3667.

    Article  PubMed  CAS  Google Scholar 

  98. Druker, B.J., et al. (2001). 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. 344:1038–1042.

    Article  PubMed  CAS  Google Scholar 

  99. Druker, B.J., et al. (2001). Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N. Engl. J. Med. 344:1031–1037.

    Article  PubMed  CAS  Google Scholar 

  100. Voutsadakis, I.A. (2001). The STI571 for the treatment of chronic myelogenous leukemia. Iatriki 80:167–171.

    Google Scholar 

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  1. Hematology Division and INSERM U487, Institut Gustave-Roussy, Villejuif, France

    Ioannis A. Voutsadakis MD

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Voutsadakis, I.A. Flt3 in acute myelogenous leukemia. Med Oncol 20, 311–323 (2003). https://doi.org/10.1385/MO:20:4:311

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