Overexpression and constitutive activation of FLT3 induces STAT5 activation in primary acute myeloid leukemia blast cells

Clinical Cancer Research

Volumn 9, Issue 6, 2003, Pages 2140-2150

  Spiekermann, Karsten ^a   Bagrintseva, Ksenia ^a   Schwab, Ruth ^a   Schmieja, Karin ^a   Hiddemann, Wolfgang ^a  

^a LUDWIG MAXIMILIANS UNIVERSITY   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

CD135 ANTIGEN; DNA; FLT3 LIGAND; FLT3 WT RECEPTOR; MITOGEN ACTIVATED PROTEIN KINASE; MONOCLONAL ANTIBODY; PROTEIN BCL 2; PROTEIN KINASE B; PROTEIN TYROSINE KINASE INHIBITOR; RECOMBINANT INTERLEUKIN 3; STAT3 PROTEIN; STAT5 PROTEIN; STEM CELL FACTOR RECEPTOR; SU 5614; TYROSINE KINASE RECEPTOR; UNCLASSIFIED DRUG;

ACUTE GRANULOCYTIC LEUKEMIA; ADULT; ARTICLE; BLAST CELL; CELL GROWTH; ENZYME ACTIVATION; FLOW CYTOMETRY; GENE DUPLICATION; GENE MUTATION; GENE OVEREXPRESSION; GENETIC TRANSDUCTION; HEMATOPOIETIC CELL; HUMAN; HUMAN CELL; IMMUNOBLOTTING; IMMUNOPRECIPITATION; INTERNAL TANDEM DUPLICATION; LENGTH MUTATION; MAJOR CLINICAL STUDY; MALIGNANT TRANSFORMATION; PHENOTYPE; PRIORITY JOURNAL; SIGNAL TRANSDUCTION;

AMINO ACID SEQUENCE; CELL TRANSFORMATION, NEOPLASTIC; DNA-BINDING PROTEINS; ENZYME ACTIVATION; FMS-LIKE TYROSINE KINASE 3; HUMANS; INDOLES; LEUKEMIA, MYELOCYTIC, ACUTE; MILK PROTEINS; MITOGEN-ACTIVATED PROTEIN KINASES; MOLECULAR SEQUENCE DATA; PHOSPHORYLATION; PROTO-ONCOGENE PROTEINS; RECEPTOR PROTEIN-TYROSINE KINASES; STAT3 TRANSCRIPTION FACTOR; STAT5 TRANSCRIPTION FACTOR; TRANS-ACTIVATORS;

EID: 0037838661     PISSN: 10780432     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (39)

1. Lisovsky, M., Estrov, Z., Zhang, X., Consoli, U., Sanchez-Williams, G., Snell, V., Munker, R., Goodacre, A., Savchenko, V., and Andreeff, M. Flt3 ligand stimulates proliferation and inhibits apoptosis of acute myeloid leukemia cells: regulation of Bcl-2 and Bax. Blood, 88: 3987-3997, 1996.
2. Abu-Duhier, F. M., Goodeve, A. C., Wilson, G. A., Care, R. S., Peake, I. R., and Reilly, J. T. Identification of novel FLT-3 Asp835 mutations in adult acute myeloid leukaemia. Br. J. Haematol., 113: 983-988, 2001.
3. Kiyoi, H., Naoe, T., Nakano, Y., Yokota, S., Minami, S., Miyawaki, S., Asou, N., Kuriyama, K., Jinnai, I., Shimazaki, C., Akiyama, H., Saito, K., Oh, H., Motoji, T., Omoto, E., Saito, H., Ohno, R., and Ueda, R. Prognostic implication of FLT3 and N-RAS gene mutations in acute myeloid leukemia. Blood, 93: 3074-3080, 1999.
4. 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. 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, 2001.
5. Meshinchi, S., Woods, W. G., Stirewalt, D. L., Sweetser, D. A., Buckley, J. D., Tjoa, T. K., Bernstein, I. D., and Radich, J. P. Prevalence and prognostic significance of Flt3 internal tandem duplication in pediatric acute myeloid leukemia. Blood, 97: 89-94, 2001.
6. Nakao, M., Yokota, S., Iwai, T., Kaneko, H., Horiike, S., Kashima, K., Sonoda, Y., Fujimoto, T., and Misawa, S. Internal tandem duplication of the flt3 gene found in acute myeloid leukemia. Leukemia (Baltimore), 10: 1911-1918, 1996.
7. Schnittger, S., Schoch, C., Dugas, M., Kern, W., Staib, P., Wuchter, C., Löffler, H., Sauerland, C-M., Serve, H., Büchner, T., Haferlach, T., and Hiddemann, W. Analysis of FLT3 length mutations in 1003 patients with acute myeloid leukemia (AML): correlation to cytogenetics. FAB subtype, and prognosis in the AMLCG study, and usefulness as a marker for detection of minimal residual disease. Blood, 100: 59-66, 2002.
8. Spiekermann, K., Bagrintseva, K., Schoch, C., Haferlach, T., Hiddemann, W., and Schnittger, S. A new and recurrent activating length mutation in exon 20 of the FLT3 gene in acute myeloid leukemia. Blood, 100: 3423-3425, 2002.
9. 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, J. E., Larson, R. A., Bloomfield, C. D., and Caligiuri, M. A. 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, 2001.
10. 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. Activating mutation of D835 within the activation loop of FLT3 in human hematologic malignancies. Blood, 97: 2434-2439, 2001.
11. Kiyoi, H., Towatari, M., Yokota, S., Hamaguchi, M., Ohno, R., Saito, H., and Naoe, T. Internal tandem duplication of the FLT3 gene is a novel modality of elongation mutation which causes constitutive activation of the product. Leukemia (Baltimore), 12: 1333-1337, 1998.
12. Wybenga-Groot, L. E., Baskin, B., Ong, S. H., Tong, J., Pawson, T., and Sicheri, F. Structural basis for autoinhibition of the ephb2 receptor tyrosine kinase by the unphosphorylated juxtamembrane region. Cell, 106: 745-757, 2001.
13. Hayakawa, F., Towatari, M., Kiyoi, H., Tanimoto, M., Kitamura, T., Saito, H., and Naoe, T. Tandem-duplicated Flt3 constitutively activates STAT5 and MAP kinase and introduces autonomous cell growth in IL-3-dependent cell lines. Oncogene, 19: 624-631, 2000.
14. 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. Flt3 mutations from patients with acute myeloid leukemia induce transformation of 32D cells mediated by the Ras and STAT5 pathways. Blood, 96: 3907-3914, 2000.
15. Spiekermann, K., Dirschinger, R. J., Schwab, R., Bagrintseva, K., Faber, F., Buske, C., Schnittger, S., Kelly, L. M., Gilliland, D. G., and Hiddemann, W. 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, 2003.
16. Kelly, L. M., Liu, Q., Kutok, J. L., Williams, I. R., Boulton, C. L., and Gilliland, D. G. 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, 2002.
17. Baldwin, B. R., Tse, K. F., and Small, D. Transgenic mice expressing a constitutively activated FLT3 receptor display a myeloproliferative disease phenotype. Blood, 98: 801a, 2001.
18. Kelly, L., Clark, J., and Gilliland, D. G. Comprehensive genotypic analysis of leukemia: clinical and therapeutic implications. Curr. Opin. Oncol., 14: 10-18, 2002.
19. Schoch, C., Schnittger, S., Bursch, S., Gerstner, D., Hochhaus, A., Berger, U., Hehlmann, R., Hiddemann, W., and Haferlach, T. Comparison of chromosome banding analysis, interphase- and hypermetaphase-FISH, qualitative and quantitative PCR for diagnosis and for follow-up in chronic myeloid leukemia: a study on 350 cases. Leukemia (Baltimore), 16: 53-59, 2002.
20. Biethahn, S., Alves, F., Wilde, S., Hiddemann, W., and Spiekermann, K. Expression of granulocyte colony-stimulating factor- and granulocyte-macrophage colony-stimulating factor-associated signal transduction proteins of the JAK/STAT pathway in normal granulopoiesis and in blast cells of acute myelogenous leukemia. Exp. Hematol., 27: 885-894, 1999.
21. Meyer, C., and Drexler, H. G. FLT3 ligand inhibits apoptosis and promotes survival of myeloid leukemia cell lines. Leuk. Lymphoma, 32: 577-581, 1999.
22. Lyman, S. D., James, L., Zappone, J., Sleath, P. R., Beckmann, M. P., and Bird, T. Characterization of the protein encoded by the flt3 (flk2) receptor-like tyrosine kinase gene. Oncogene, 8: 815-822, 1993.
23. Zhang, S., Fukuda, S., Lee, Y., Hangoc, G., Cooper, S., Spolski, R., Leonard, W. J., and Broxmeyer, H. E. Essential role of signal transducer and activator of transcription (Stat)5a but not Stat5b for Flt3-dependent signaling. J. Exp. Med. 192: 719-728, 2000.
24. Birkenkamp, K. U., Geugien, M., Lemmink, H. H., Kruijer, W., and Vellenga, E. Regulation of constitutive STAT5 phosphorylation in acute myeloid leukemia blasts. Leukemia (Baltimore), 15: 1923-1931, 2001.
25. Benekli, M., Xia, Z., Donohue, K. A., Ford, L. A., Pixley, L. A., Baer, M. R., Baumann, H., and Wetzler, M. Constitutive activity of signal transducer and activator of transcription 3 protein in acute myeloid leukemia blasts is associated with short disease-free survival. Blood, 99: 252-257, 2002.
26. Gouilleux-Gruart, V., Gouilleux, F., Desaint, C., Claisse, J. F., Capiod, J. C., Delobel, J., Weber-Nordt, R., Dusanter-Fourt, I., Dreyfus, F., Groner, B., and Prin, L. STAT-related transcription factors are constitutively activated in peripheral blood cells from acute leukemia patients. Blood, 87: 1692-1697, 1996.
27. Hayakawa, F., Towatari, M., Iida, H., Wakao, H., Kiyoi, H., Naoe, T., and Saito, H. Differential constitutive activation between STAT-related proteins and MAP kinase in primary acute myelogenous leukaemia. Br. J. Haematol., 101: 521-528, 1998.
28. Schuringa, J. J., Wierenga, A. T., Kruijer, W., and Vellenga, E. Constitutive Stat3. Tyr705, and Ser727 phosphorylation in acute myeloid leukemia cells caused by the autocrine secretion of interleukin-6. Blood, 95: 3765-3770, 2000.
29. Spiekermann, K., Biethahn, S., Wilde, S., Hiddemann, W., and Alves, F. Constitutive activation of STAT transcription factors in acute myelogenous leukemia. Eur. J. Haematol., 67: 63-71, 2001.
30. Weber-Nordt, R. M., Egen, C., Wehinger, J., Ludwig, W., Gouilleux-Gruart, V., Mertelsmann, R., and Finke, J. Constitutive activation of STAT proteins in primary lymphoid and myeloid leukemia cells and in Epstein-Barr virus (EBV)-related lymphoma cell lines. Blood, 88: 809-816, 1996.
31. Xia, Z., Baer, M. R., Block, A. W., Baumann, H., and Wetzler, M. Expression of signal transducers and activators of transcription proteins in acute myeloid leukemia blasts. Cancer Res., 58: 3173-3180, 1998.
32. Grundler, R., Miething, C., Thiede, C., Peschel, C., and Duyster, J. Mimicking a hemizygous FLT3 ITD genotype versus a heterozygous FLT3 ITD/WT genotype does not result in growth advantage in Ba/F3 and 32D cells (abstract). Onkologie, 25: 158, 2002.
33. Birg, F., Courcoul, M., Rosnet, O., Bardin, F., Pebusque, M. J., Marchetto, S., Tabilio, A., Mannoni, P., and Birnbaum, D. Expression of the FMS/KIT-like gene FLT3 in human acute leukemias of the myeloid and lymphoid lineages. Blood, 80: 2584-2593, 1992.
34. Carow, C. E., Levenstein, M., Kaufmann, S. H., Chen, J., Amin, S., Rockwell, P., Witte, L., Borowitz, M. J., Civin, C. I., and Small, D. Expression of the hematopoietic growth factor receptor FLT3 (STK-1/Flk2) in human leukemias. Blood, 87: 1089-1096, 1996.
35. Rosnet, O., Buhring, H. J., Marchetto, S., Rappold, I., Lavagna, C., Sainty, D., Arnoulet, C., Chabannon, C., Kanz, L., Hannum, C., and Birnbaum, D. Human FLT3/FLK2 receptor tyrosine kinase is expressed at the surface of normal and malignant hematopoietic cells. Leukemia (Baltimore), 10: 238-248, 1996.
36. Stacchini, A., Fubini, L., Severino, A., Sanavio, F., Aglietta, M., and Piacibello, W. Expression of type III receptor tyrosine kinases FLT3 and KIT and responses to their ligands by acute myeloid leukemia blasts. Leukemia (Baltimore), 10: 1584-1591, 1996.
37. Nosaka, T., Kawashima, T., Misawa, K., Ikuta, K., Mui, A. L., and Kitamura, T. STAT5 as a molecular regulator of proliferation, differentiation and apoptosis in hematopoietic cells. EMBO J., 18: 4754-4765, 1999.
38. Spiekermann, K., Schwab, R., Pau, M., Schmieja, K., Franzrahe, S., and Hiddemann, W. Constitutive activation of STAT3 and STAT5 is induced by leukemic fusion proteins with protein tyrosine kinase activity and is sufficient for transformation of hematopoietic precursor cells. Exp. Hematol., 30: 262-271, 2002.
39. Schwaller, J., Parganas, E., Wang, D., Cain, D., Aster, J. C., Williams, I. R., Lee, C. K., Gerthner, R., Kitamura, T., Frantsve, J., Anastasiadou, E., Loh, M. L., Levy, D. E., Ihle, J. N., and Gilliland, D. G. Stat5 is essential for the myelo- and lymphoproliferative disease induced by TEL/JAK2. Mol. Cell, 6: 693-704, 2000.