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Expression of the FMS/KIT-like gene FLT3 in human acute leukemias of the
myeloid and lymphoid lineages
F Birg, M Courcoul, O Rosnet, F Bardin, MJ Pebusque, S Marchetto, A Tabilio, P Mannoni and D Birnbaum
Laboratory of Molecular Hematology, Unite 119 de l'INSERM, Marseille,
France.
FLT3, a receptor belonging to the FMS/KIT family and localized to 13q12,
could play a role in the biology of early hematopoietic progenitor cells.
Because FMS and KIT are expressed in both normal progenitors and myeloid
leukemias, we looked for FLT3 expression in fresh human leukemic cells
using Northern blot analysis. High levels of FLT3 expression were detected
in 92% of the cases of acute myeloid leukemia (AML) tested, ranging from
the M1 to the M5 stages of differentiation assessed in the
French-American-British classification. Immature (MO) AML cells,
biphenotypic leukemias, and AML with megakaryocytic differentiation (M7
subtype) also expressed the FLT3 transcript. FLT3 was also expressed at
high levels in acute lymphoid leukemias of T and B origins. Finally, it was
not expressed in chronic myeloid leukemias in chronic phase, whereas it was
expressed in most blast crisis samples. This pattern of expression of FLT3
contrasts with the expression of FMS and KIT restricted to myeloid
leukemias, and suggests that the FLT3 product could play a role in the
expansion of the leukemic blasts of both the myeloid and lymphoid lineages.
Volume 80,
Issue 10,
pp. 2584-2593,
11/15/1992
Copyright © 1992 by The American Society of Hematology
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23(16):
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109(4):
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108(10):
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108(10):
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66(9):
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|
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|
|
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|
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|
|
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280(7):
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[Full Text]
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|
|
|
|
|
|
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105(4):
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|
|
|
|
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|
|
|
|
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|
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104(9):
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|
|
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|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
|
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|
|
|
|
|
|
|
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|
|
|
|
|
|
|
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100(5):
1532 - 1542.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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Blood,
May 29, 2002;
99(12):
4326 - 4335.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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Blood,
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99(11):
3885 - 3891.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. M. Kelly, Q. Liu, J. L. Kutok, I. R. Williams, C. L. Boulton, and D. G. Gilliland
FLT3 internal tandem duplication mutations associated with human acute myeloid leukemias induce myeloproliferative disease in a murine bone marrow transplant model
Blood,
January 1, 2002;
99(1):
310 - 318.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Levis, K.-F. Tse, B. D. Smith, E. Garrett, and D. Small
A FLT3 tyrosine kinase inhibitor is selectively cytotoxic to acute myeloid leukemia blasts harboring FLT3 internal tandem duplication mutations
Blood,
August 1, 2001;
98(3):
885 - 887.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. B. Pawlowska, S. Hashino, H. McKenna, B. J. Weigel, P. A. Taylor, and B. R. Blazar
In vitro tumor-pulsed or in vivo Flt3 ligand-generated dendritic cells provide protection against acute myelogenous leukemia in nontransplanted or syngeneic bone marrow-transplanted mice
Blood,
March 1, 2001;
97(5):
1474 - 1482.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Guasch, G. J. Mack, C. Popovici, N. Dastugue, D. Birnbaum, J. B. Rattner, and M.-J. Pebusque
FGFR1 is fused to the centrosome-associated protein CEP110 in the 8p12 stem cell myeloproliferative disorder with t(8;9)(p12;q33)
Blood,
March 1, 2000;
95(5):
1788 - 1796.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Popovici, B. Zhang, M.-J. Gregoire, P. Jonveaux, M. Lafage-Pochitaloff, D. Birnbaum, and M.-J. Pebusque
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Blood,
February 15, 1999;
93(4):
1381 - 1389.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. S. Hawley, A. Z.C. Fong, H. Griesser, S. D. Lyman, and R. G. Hawley
Leukemic Predisposition of Mice Transplanted With Gene-Modified Hematopoietic Precursors Expressing flt3 Ligand
Blood,
September 15, 1998;
92(6):
2003 - 2011.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Lavagna-Sevenier, S. Marchetto, D. Birnbaum, and O. Rosnet
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J. Biol. Chem.,
June 12, 1998;
273(24):
14962 - 14967.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. D. Lyman and S. E. W. Jacobsen
c-kit Ligand and Flt3 Ligand: Stem/Progenitor Cell Factors With Overlapping Yet Distinct Activities
Blood,
February 15, 1998;
91(4):
1101 - 1134.
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Rappold, B. L. Ziegler, I. Kohler, S. Marchetto, O. Rosnet, D. Birnbaum, P. J. Simmons, A. C.W. Zannettino, B. Hill, S. Neu, et al.
Functional and Phenotypic Characterization of Cord Blood and Bone Marrow Subsets Expressing FLT3 (CD135) Receptor Tyrosine Kinase
Blood,
July 1, 1997;
90(1):
111 - 125.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R Namikawa, M. Muench, and M. Roncarolo
Regulatory roles of the ligand for Flk2/Flt3 tyrosine kinase receptor on human hematopoiesis
Stem Cells,
July 1, 1996;
14(4):
388 - 395.
[Abstract]
|
|
|
|
|
