Suppression of myeloid transcription factors and induction of STAT response genes by AML-specific Flt3 mutations

Blood

Volumn 101, Issue 8, 2003, Pages 3164-3173

  Mizuki, Masao ^b   Schwäble, Joachim ^b   Steur, Claudia ^b   Choudhary, Chunaram ^b   Agrawal, Shuchi ^b   Sargin, Bülent ^b   Steffen, Björn ^b   Matsumura, Itaru ^b   Kanakura, Yuzuru ^b   Böhmer, Frank D ^b   Müller Tidow, Carsten ^b   Berdel, Wolfgang E ^b   Serve, Hubert ^a  

^a UNIVERSITY OF MÜNSTER   (Germany)

^b NONE

Author keywords

[No Author keywords available]

Indexed keywords

CCAAT ENHANCER BINDING PROTEIN ALPHA; FLT3 LIGAND; INTERLEUKIN 3 RECEPTOR; ISOPROTEIN; MESSENGER RNA; MUTANT PROTEIN; PROTEIN PIM 2; PROTEIN SERINE THREONINE KINASE; PROTEIN TYROSINE KINASE; STAT PROTEIN; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR PU 1; UNCLASSIFIED DRUG; CD135 ANTIGEN; FLT3 PROTEIN, HUMAN; FLT3 PROTEIN, MOUSE; HYBRID PROTEIN; INTERLEUKIN 3; ONCOPROTEIN; PIM2 PROTEIN, HUMAN; PIM2 PROTEIN, MOUSE; PROTO ONCOGENE PROTEIN SPI 1; PROTO-ONCOGENE PROTEIN SPI-1; SYNTHETIC DNA; TRANSACTIVATOR PROTEIN; TUMOR PROTEIN;

ACUTE GRANULOCYTIC LEUKEMIA; ANIMAL CELL; ARTICLE; BLAST TRANSFORMATION; CELL CLONE; CELL GROWTH; CELL LEVEL; CELL LINE; CONTROLLED STUDY; DNA MICROARRAY; ENZYME ACTIVITY; GENE ACTIVATION; GENE EXPRESSION; GENE EXPRESSION REGULATION; GENE STRUCTURE; GENE TARGETING; GENETIC TRANSFECTION; GENOME ANALYSIS; HUMAN; HUMAN CELL; LIGAND BINDING; MOLECULAR MIMICRY; MOUSE; NONHUMAN; NUCLEOTIDE SEQUENCE; ONCOGENE; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN INDUCTION; PROTEIN STRUCTURE; SEQUENCE HOMOLOGY; TANDEM REPEAT; TRANSCRIPTION INITIATION; UNINDEXED SEQUENCE; UPREGULATION; WILD TYPE; ACUTE DISEASE; ANIMAL; BIOSYNTHESIS; BONE MARROW CELL; CLUSTER ANALYSIS; COMPUTER SYSTEM; GENE EXPRESSION PROFILING; GENETIC TRANSCRIPTION; GENETICS; HEMATOPOIETIC STEM CELL; METABOLISM; MYELOID LEUKEMIA; PATHOLOGY; PHYSIOLOGY; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION;

ACUTE DISEASE; ANIMALS; CCAAT-ENHANCER-BINDING PROTEIN-ALPHA; CELL LINE; CLUSTER ANALYSIS; COMPUTER SYSTEMS; FMS-LIKE TYROSINE KINASE 3; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; GENE EXPRESSION REGULATION, LEUKEMIC; GENES, SYNTHETIC; HEMATOPOIETIC STEM CELLS; HUMANS; INTERLEUKIN-3; LEUKEMIA, MYELOID; MICE; MYELOID CELLS; NEOPLASM PROTEINS; OLIGONUCLEOTIDE ARRAY SEQUENCE ANALYSIS; PROTEIN ISOFORMS; PROTEIN-SERINE-THREONINE KINASES; PROTO-ONCOGENE PROTEINS; RECEPTOR PROTEIN-TYROSINE KINASES; RECOMBINANT FUSION PROTEINS; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; TANDEM REPEAT SEQUENCES; TRANS-ACTIVATORS; TRANSCRIPTION, GENETIC; TRANSFECTION;

EID: 0037944120     PISSN: 00064971     EISSN: None     Source Type: Journal    
DOI: 10.1182/blood-2002-06-1677     Document Type: Article

References (50)

1. Lyman SD, Jacobsen SE. c-kit ligand and Flt3 ligand: stem/progenitor cell factors with overlapping yet distinct activities. Blood. 1998;91:1101-1134.
2. 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;11:1605-1609.
3. Nakao M, Yokota S, Iwai T, et al. Internal tandem duplication of the flt3 gene found in acute myeloid leukemia. Leukemia. 1996;10:1911-1918.
4. Hayakawa F, Towatari M, Kiyoi H, et al. Tandem-duplicated Flt3 constitutively activates STAT5 and MAP kinase and introduces autonomous cell growth in IL-3-dependent cell lines. Oncogene. 2000;19:624-631.
5. Kelly LM, Liu Q, Kutok JL, Williams IR, Boulton CL, Gilliland DG. FLT3 internal tandem duplication mutations associated with human acute myeloid leukemias induce myeloproliferative disease in a murine bone marrow transplant model. Blood. 2002;99:310-318.
6. Mizuki M, Fenski R, Halfter H, et al. Flt3 mutations from patients with acute myeloid leukemia induce transformation of 32D cells mediated by the Ras and STAT5 pathways. Blood. 2000;96:3907-3914.
7. Tse KF, Mukherjee G, Small D. Constitutive activation of FLT3 stimulates multiple intracellular signal transducers and results in transformation. Leukemia. 2000;14:1766-1776.
8. 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;61:7233-7239.
9. 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;98:1752-1759.
10. Meshinchi S, Woods WG, Stirewalt DL, et al. Prevalence and prognostic significance of Flt3 internal tandem duplication in pediatric acute myeloid leukemia. Blood. 2001;97:89-94.
11. 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;111:190-195.
12. Rombouts WJ, Blokland I, Lowenberg B, Ploemacher RE. Biological characteristics and prognosis of adult acute myeloid leukemia with internal tandem duplications in the Flt3 gene. Leukemia. 2000;14:675-683.
13. Kiyoi H, Naoe T, Nakano Y, et al. Prognostic implication of FLT3 and N-RAS gene mutations in acute myeloid leukemia. Blood. 1999;93:3074-3080.
14. Fenski R, Flesch K, Serve S, et al. Constitutive activation of FLT3 in acute myeloid leukaemia and its consequences for growth of 32D cells. Br J Haematol. 2000;108:322-330.
15. Abu-Duhier FM, Goodeve AC, Wilson GA, Care RS, Peake IR, Reilly JT. Identification of novel FLT-3 Asp835 mutations in adult acute myeloid leukaemia. Br J Haematol. 2001;113:983-988.
16. Yamamoto Y, Kiyoi H, Nakano Y, et al. Activating mutation of D835 within the activation loop of FLT3 in human hematologic malignancies. Blood. 2001;97:2434-2439.
17. Redner RL, Wang J, Liu JM. Chromatin remodeling and leukemia: new therapeutic paradigms. Blood. 1999;94:417-428.
18. Teller S, Kramer D, Bohmer SA, et al. Bis(1H-2-indolyl)-1-methanones as inhibitors of the hematopoietic tyrosine kinase Flt3. Leukemia. 2002;16:1528-1534.
19. Buchner T, Hiddemann W, Wormann B, et al. Double induction strategy for acute myeloid leukemia: the effect of high-dose cytarabine with mitoxantrone instead of standard-dose cytarabine with daunorubicin and 6-thioguanine: a randomized trial by the German AML Cooperative Group. Blood. 1999;93:4116-4124.
20. Allen JD, Verhoeven E, Domen J, van der Valk M, Berns A. Pim-2 transgene induces lymphoid tumors, exhibiting potent synergy with c-myc. Oncogene. 1997;15:1133-1141.
21. Tusher VG, Tibshirani R, Chu G. Significance analysis of microarrays applied to the ionizing radiation response. Proc Natl Acad Sci U S A. 2001;98:5116-5121.
22. Eisen MB, Spellman PT, Brown PO, Botstein D. Cluster analysis and display of genome-wide expression patterns. Proc Natl Acad Sci U S A. 1998;95:14863-14868.
23. Muller C, Readhead C, Diederichs S, et al. Methylation of the cyclin A1 promoter correlates with gene silencing in somatic cell lines, while tissue-specific expression of cyclin A1 is methylation independent. Mol Cell Biol. 2000;20:3316-3329.
24. Matsumura I, Kawasaki A, Tanaka H, et al. Biologic significance of GATA-1 activities in Ras-mediated megakaryocytic differentiation of hematopoietic cell lines. Blood. 2000;96:2440-2450.
25. Nosaka T, Kawashima T, Misawa K, Ikuta K, Mui AL, Kitamura T. STAT5 as a molecular regulator of proliferation, differentiation and apoptosis in hematopoietic cells. EMBO J. 1999;18:4754-4765.
26. Shirogane T, Fukada T, Muller JM, Shima DT, Hibi M, Hirano T. Synergistic roles for Pim-1 and c-Myc in STAT3-mediated cell cycle progression and antiapoptosis. Immunity. 1999;11:709-719.
27. Chen XP, Losman JA, Cowan S, et al. Pim serine/threonine kinases regulate the stability of Socs-1 protein. Proc Natl Acad Sci U S A. 2002;99:2175-2180.
28. Friedman AD. Transcriptional regulation of granulocyte and monocyte development. Oncogene. 2002;21:3377-3390.
29. DeKoter RP, Singh H. Regulation of B lymphocyte and macrophage development by graded expression of PU.1. Science. 2000;288:1439-1441.
30. Adolfsson J, Borge OJ, Bryder D, et al. Upregulation of Flt3 expression within the bone marrow Lin(-)Sca1(+) c-kit(+) stem cell compartment is accompanied by loss of self-renewal capacity. Immunity. 2001;15:659-669.
31. Westendorf JJ, Yamamoto CM, Lenny N, Downing JR, Selsted ME, Hiebert SW. The t(8;21) fusion product, AML-1-ETO, associates with C/EBP-α, inhibits C/EBP-α-dependent transcription, and blocks granulocytic differentiation. Mol Cell Biol. 1998;18:322-333.
32. Spiekermann K, Pau M, Schwab R, Schmieja K, Franzrahe S, 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. 2002;30:262-271.
33. Sternberg DW, Tomasson MH, Carroll M, et al. The TEL/PDGFbetaR fusion in chronic myelomonocytic leukemia signals through STAT5-dependent and STAT5-independent pathways. Blood. 2001;98:3390-3397.
34. Ning ZQ, Li J, Arceci RJ. Signal transducer and activator of transcription 3 activation is required for Asp(816) mutant c-Kit-mediated cytokine-independent survival and proliferation in human leukemia cells. Blood. 2001;97:3559-3567.
35. Zhang S, Fukuda S, Lee Y, et al. Essential role of signal transducer and activator of transcription (Stat)5a but not Stat5b for Flt3-dependent signaling. J Exp Med. 2000;192:719-728.
36. Dhanasekaran SM, Barrette TR, Ghosh D, et al. Delineation of prognostic biomarkers in prostate cancer. Nature. 2001;412:822-826.
37. Krebs DL, Hilton DJ. SOCS proteins: negative regulators of cytokine signaling. Stem Cells. 2001;19:378-387.
38. Schultheis B, Carapeti-Marootian M, Hochhaus A, Weisser A, Goldman JM, Melo JV. Overexpression of SOCS-2 in advanced stages of chronic myeloid leukemia: possible inadequacy of a negative feedback mechanism. Blood. 2002;99:1766-1775.
39. Wang QF, Friedman AD. CCAAT/enhancer-binding proteins are required for granulopoiesis independent of their induction of the granulocyte colony-stimulating factor receptor. Blood. 2002;99:2776-2785.
40. Pabst T, Mueller BU, Harakawa N, et al. AML1-ETO downregulates the granulocytic differentiation factor C/EBPα in t(8;21) myeloid leukemia. Nat Med. 2001;7:444-451.
41. Burel SA, Harakawa N, Zhou L, Pabst T, Tenen DG, Zhang DE. Dichotomy of AML1-ETO functions: growth arrest versus block of differentiation Mol Cell Biol. 2001;21:5577-5590.
42. Pabst T, Mueller BU, Zhang P, et al. Dominant-negative mutations of CEBPA, encoding CCAAT/enhancer binding protein-α (C/EBPα), in acute myeloid leukemia. Nat Genet. 2001;27:263-270.
43. Gombart AF, Hofmann WK, Kawano S, et al. Mutations in the gene encoding the transcription factor CCAAT/enhancer binding protein α in myelodysplastic syndromes and acute myeloid leukemias. Blood. 2002;99:1332-1340.
44. Wang H, Iakova P, Wilde M, et al. C/EBPα arrests cell proliferation through direct inhibition of Cdk2 and Cdk4. Mol Cell. 2001;8:817-828.
45. Wang H, Goode T, Iakova P, Albrecht JH, Timchenko NA. C/EBPα triggers proteasome-dependent degradation of cdk4 during growth arrest. EMBO J. 2002;21:930-941.
46. Porse BT, Pedersen TA, Xu X, et al. E2F repression by C/EBPα is required for adipogenesis and granulopoiesis in vivo. Cell. 2001;107:247-258.
47. Johansen LM, Iwama A, Lodie TA, et al. c-Myc is a critical target for c/EBPα in granulopoiesis. Mol Cell Biol. 2001;21:3789-3806.
48. Deguchi K, Gilliland DG. Cooperativity between mutations in tyrosine kinases and in hematopoietic transcription factors in AML. Leukemia. 2002;16:740-744.
49. Mulloy JC, Cammenga J, MacKenzie KL, Berguido FJ, Moore MA, Nimer SD. The AML1-ETO fusion protein promotes the expansion of human hematopoietic stem cells. Blood. 2002;99:15-23.
50. Shimada H, Ichikawa H, Nakamura S, et al. Analysis of genes under the downstream control of the t(8;21) fusion protein AML1-MTG8: overexpression of the TIS11b (ERF-1, cMG1) gene induces myeloid cell proliferation in response to G-CSF. Blood. 2000;96:655-663.