The role of FLT3 in haematopoietic malignancies

Nature Reviews Cancer

Volumn 3, Issue 9, 2003, Pages 650-665

  Stirewalt, Derek L ^a   Radich, Jerald P ^a  

^a UNIVERSITY OF WASHINGTON   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 [6 METHOXY 7 [3 (1 PIPERIDINYL)PROPOXY] 4 QUINAZOLINYL] 1 PIPERAZINECARBOXYLIC ACID (4 ISOPROPOXYPHENYL)AMIDE; 5,6,7,13 TETRAHYDRO 12 (3 HYDROXYPROPYL) 9 ISOPROPOXYMETHYLINDENO[2,1 A]PYRROLO[3,4 C]CARBAZOL 5(12H) ONE; 6,7 DIMETHOXY 2 PHENYLQUINOXALINE; 6,7 DIMETHYL 2 PHENYLQUINOXALINE; CEP 701; FLT3 INHIBITOR; FLT3 LIGAND; HERBIMYCIN A; IMATINIB; L 000021649; MIDOSTAURIN; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN TYROSINE KINASE; RAS PROTEIN; SEMAXANIB; SU 5614; SUNITINIB; UNCLASSIFIED DRUG; CD135 ANTIGEN; CELL SURFACE RECEPTOR; FLT3 LIGAND PROTEIN; FLT3 PROTEIN, HUMAN; LIGAND; MEMBRANE PROTEIN; ONCOPROTEIN;

ACUTE GRANULOCYTIC LEUKEMIA; APOPTOSIS; BASE PAIRING; CARCINOGENESIS; CELL DEATH; CELL DIFFERENTIATION; CELL PROLIFERATION; DIMERIZATION; EXON; FMS LIKE TYROSINE KINASE 3 GENE; GENE; GENE ACTIVATION; GENE EXPRESSION; GENE MUTATION; GENE STRUCTURE; HEMATOPOIESIS; HEMATOPOIETIC CELL; HEMATOPOIETIC SYSTEM TUMOR; HUMAN; INTERNAL TANDEM DUPLICATION; OUTCOMES RESEARCH; POINT MUTATION; PREVALENCE; PRIORITY JOURNAL; PROTEIN DOMAIN; REVIEW; SIGNAL TRANSDUCTION; TANDEM REPEAT; TYROSINE KINASE DOMAIN; ACUTE DISEASE; BIOSYNTHESIS; BLOOD DISEASE; CELL DIVISION; CELL TRANSFORMATION; GENETICS; IMMUNE SYSTEM; IMMUNOLOGY; MUTATION; MYELOID LEUKEMIA;

ACUTE DISEASE; CELL DIVISION; CELL TRANSFORMATION, NEOPLASTIC; FMS-LIKE TYROSINE KINASE 3; HEMATOLOGIC NEOPLASMS; HUMANS; IMMUNE SYSTEM; LEUKEMIA, MYELOID; LIGANDS; MEMBRANE PROTEINS; MUTATION; PROTO-ONCOGENE PROTEINS; RECEPTOR PROTEIN-TYROSINE KINASES; RECEPTORS, CELL SURFACE; SIGNAL TRANSDUCTION;

EID: 0141465061     PISSN: 1474175X     EISSN: None     Source Type: Journal    
DOI: 10.1038/nrc1169     Document Type: Review

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105. Libura, M. et al. FLT3 and MLL intragenic abnormalities in AML reflect a common category of genotoxic stress. Blood Jun 5 2003 (doi: 10, 1182/blood-2003-01-0162). This paper was the first to examine the possible correlations between MLL abnormalities and expression of FLT3 in patient samples.
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109. Whitman, S. P. 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. 61, 7233-7239 (2001). One of the first studies to indicate that the ITD:wild-type ratio of FLT3 might have prognostic impact in patients with AML.
110. Armstrong, S. A. et al. Inhibition of FLT3 in MLL. Validation of a therapeutic target identified by gene expression based classification. Cancer Cell 3, 173-183 (2003). This study was the first to show that inhibition of FLT3 over-expression in a cell with MLL abnormalities could block the growth of these cells, and it provided the rationale for examining FLT3 inhibitors in other leukaemia cells that over-express FLT3.
111. Druker, B. J. & Lydon, N. B. Lessons learned from the development of an abl tyrosine kinase inhibitor for chronic myelogenous leukemia. J. Clin. Invest. 105, 3-7 (2000).
112. Zhao, M. et al. In vivo treatment of mutant FLT3-transformed murine leukemia with a tyrosine kinase inhibitor. Leukemia 14, 374-378 (2000).
113. Levis, M., Tse, K. F., Smith, B. D., Garrett, E. & Small, D. A FLT3 tyrosine kinase inhibitor is selectively cytotoxic to acute myeloid leukemia blasts harboring FLT3 internal tandem duplication mutations. Blood 98, 885-887 (2001). References 112 and 113 were the first to show that activation-mutant FLT3 could be blocked with tyrosine-kinase inhibitors, and that this inhibition caused apoptosis.
114. Tse, K. F. et al. Inhibition of the transforming activity of FLT3 internal tandem duplication mutants from AML patients by a tyrosine kinase inhibitor. Leukemia 16, 2027-2036 (2002).
115. Minami, Y. et al. Selective apoptosis of tandemly duplicated FLT3-transformed leukemia cells by Hsp90 inhibitors. Leukemia 16, 1535-1540 (2002).
116. Levis, M. et al. A FLT3-targeted tyrosine kinase inhibitor is cytotoxic to leukemia cells in vitro and in vivo. Blood 99, 3885-3891 (2002).
117. Levis, M. et al. FLT3-targeted inhibitors kill FLT3-dependent modeled cells, leukemia-derived cell lines, and primary AML blasts in vitro and in vivo. Blood 89, 721a (2001).
118. Smith. B. D. et al. Single agent CEP-701, a novel FLT-3 inhibitor, shows initial response in patients with refactory acute myeloid leukemia. Blood 100, 314a (2002).
119. O'Farrell, A. M. et al. SU11248 is a novel FLT3 tyrosine kinase inhibitor with potent activity in vitro and in vivo. Blood 101, 3597-3605 (2003).
120. Yee, K. W. et al. SU5416 and SU5614 inhibit kinase activity of wild-type and mutant FLT3 receptor tyrosine kinase. Blood 100, 2941-2949 (2002).
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