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STAT-related transcription factors are constitutively activated in
peripheral blood cells from acute leukemia patients
V Gouilleux-Gruart, F Gouilleux, C Desaint, JF Claisse, JC Capiod, J Delobel, R Weber-Nordt, I Dusanter-Fourt, F Dreyfus, B Groner and L Prin
Laboratoire d'Immunologie, Centre Hospitalier Universitaire d'Amiens,
France.
A signal transduction pathway activated by many cytokines has recently been
elaborated. The JAK kinases and the signal transducers and activators of
transcription (STAT) factors have been found to be essential components. In
this report, we describe the presence of constitutively activated STAT
factors in peripheral blood cells from patients with acute leukemia. We
used oligonucleotide probes from the beta-casein and IRF-1 gene promoters
and the ISRE probe to detect STAT proteins in nuclear extracts from acute
leukemia cells in bandshift assays. Specific DNA protein complex formation
was observed with the probes from the beta-casein and IRF-1 gene promoters,
but not with the ISRE oligonucleotide probe, when cell extracts from acute
lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) were
investigated. We used nonradioactive oligonucleotides as competitors to
show the specificity of the complex formation. Specific antibodies directed
against the individual STAT proteins were used in supershift experiments.
STAT5- and STAT1-related factors were detected in ALL and STAT1-, STAT3-,
and STAT5-related proteins were present in nuclear cell extracts from AML.
Since the cells were not treated with cytokines before the nuclear proteins
were extracted, we conclude that these factors are constitutively activated
in vivo. It is likely that the constitutive activation of STAT proteins is
a part of the events of leukemogenesis.
Volume 87,
Issue 5,
pp. 1692-1697,
03/01/1996
Copyright © 1996 by The American Society of Hematology
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Signal Transducer and Activator of Transcription (STAT)5 Activation by BCR/ABL Is Dependent on Intact Src Homology (SH)3 and SH2 Domains of BCR/ABL and Is Required for Leukemogenesis
J. Exp. Med.,
April 19, 1999;
189(8):
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[Abstract]
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R. Y. Liu, C. Fan, R. Garcia, R. Jove, and K. S. Zuckerman
Constitutive Activation of the JAK2/STAT5 Signal Transduction Pathway Correlates With Growth Factor Independence of Megakaryocytic Leukemic Cell Lines
Blood,
April 1, 1999;
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2369 - 2379.
[Abstract]
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C. Boucheron, S. Dumon, S. C. R. Santos, R. Moriggl, L. Hennighausen, S. Gisselbrecht, and F. Gouilleux
A Single Amino Acid in the DNA Binding Regions of STAT5A and STAT5B Confers Distinct DNA Binding Specificities
J. Biol. Chem.,
December 18, 1998;
273(51):
33936 - 33941.
[Abstract]
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C. S. Zong, L. Zeng, Y. Jiang, H. B. Sadowski, and L.-H. Wang
Stat3 Plays an Important Role in Oncogenic Ros- and Insulin-like Growth Factor I Receptor-induced Anchorage-independent Growth
J. Biol. Chem.,
October 23, 1998;
273(43):
28065 - 28072.
[Abstract]
[Full Text]
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L. M.L. Tuyt, K. Bregman, C. Lummen, W. H.A. Dokter, and E. Vellenga
Differential Binding Activity of the Transcription Factor LIL-Stat in Immature and Differentiated Normal and Leukemic Myeloid Cells
Blood,
August 15, 1998;
92(4):
1364 - 1373.
[Abstract]
[Full Text]
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K. Kirito, M. Uchida, M. Takatoku, K. Nakajima, T. Hirano, Y. Miura, and N. Komatsu
A Novel Function of Stat1alpha and Stat3 Proteins in Erythropoietin-Induced Erythroid Differentiation of a Human Leukemia Cell Line
Blood,
July 15, 1998;
92(2):
462 - 471.
[Abstract]
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M. Onishi, T. Nosaka, K. Misawa, A. L.-F. Mui, D. Gorman, M. McMahon, A. Miyajima, and T. Kitamura
Identification and Characterization of a Constitutively Active STAT5 Mutant That Promotes Cell Proliferation
Mol. Cell. Biol.,
July 1, 1998;
18(7):
3871 - 3879.
[Abstract]
[Full Text]
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M. Chatterjee-Kishore, R. Kishore, D. J. Hicklin, F. M. Marincola, and S. Ferrone
Different Requirements for Signal Transducer and Activator of Transcription 1alpha and Interferon Regulatory Factor 1 in the Regulation of Low Molecular Mass Polypeptide 2 and Transporter Associated with Antigen Processing 1 Gene Expression
J. Biol. Chem.,
June 26, 1998;
273(26):
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[Abstract]
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J. Turkson, T. Bowman, R. Garcia, E. Caldenhoven, R. P. De Groot, and R. Jove
Stat3 Activation by Src Induces Specific Gene Regulation and Is Required for Cell Transformation
Mol. Cell. Biol.,
May 1, 1998;
18(5):
2545 - 2552.
[Abstract]
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J. F. Bromberg, C. M. Horvath, D. Besser, W. W. Lathem, and J. E. Darnell Jr.
Stat3 Activation Is Required for Cellular Transformation by v-src
Mol. Cell. Biol.,
May 1, 1998;
18(5):
2553 - 2558.
[Abstract]
[Full Text]
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C. A. Myers, C. Schmidhauser, J. Mellentin-Michelotti, G. Fragoso, C. D. Roskelley, G. Casperson, R. Mossi, P. Pujuguet, G. Hager, and M. J. Bissell
Characterization of BCE-1, a Transcriptional Enhancer Regulated by Prolactin and Extracellular Matrix and Modulated by the State of Histone Acetylation
Mol. Cell. Biol.,
April 1, 1998;
18(4):
2184 - 2195.
[Abstract]
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R. Moriggl, C. Kristofic, B. Kinzel, S. Volarevic, B. Groner, and V. Brinkmann1
Activation of STAT Proteins and Cytokine Genes in Human Th1 and Th2 Cells Generated in the Absence of IL-12 and IL-4
J. Immunol.,
April 1, 1998;
160(7):
3385 - 3392.
[Abstract]
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W. H. Sun, C. Pabon, Y. Alsayed, P. P. Huang, S. Jandeska, S. Uddin, L. C. Platanias, and S. T. Rosen
Interferon-alpha Resistance in a Cutaneous T-Cell Lymphoma Cell Line Is Associated With Lack of STAT1 Expression
Blood,
January 15, 1998;
91(2):
570 - 576.
[Abstract]
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S. Takemoto, J. C. Mulloy, A. Cereseto, T.-S. Migone, B. K. R. Patel, M. Matsuoka, K. Yamaguchi, K. Takatsuki, S. Kamihira, J. D. White, et al.
Proliferation of adult T cell leukemia/lymphoma cells is associated with the constitutive activation of JAK/STAT proteins
PNAS,
December 9, 1997;
94(25):
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[Abstract]
[Full Text]
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P. Saharinen, N. Ekman, K. Sarvas, P. Parker, K. Alitalo, and O. Silvennoinen
The Bmx Tyrosine Kinase Induces Activation of the Stat Signaling Pathway, Which Is Specifically Inhibited by Protein Kinase Cdelta
Blood,
December 1, 1997;
90(11):
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[Abstract]
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M. Nielsen, K. Kaltoft, M. Nordahl, C. Ropke, C. Geisler, T. Mustelin, P. Dobson, A. Svejgaard, and N. Odum
Constitutive activation of a slowly migrating isoform of Stat3 in mycosis fungoides: Tyrphostin AG490 inhibits Stat3 activation and growth of mycosis fungoides tumor cell lines
PNAS,
June 24, 1997;
94(13):
6764 - 6769.
[Abstract]
[Full Text]
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J. Odajima, I. Matsumura, J. Sonoyama, H. Daino, A. Kawasaki, H. Tanaka, N. Inohara, T. Kitamura, J. Downward, K. Nakajima, et al.
Full Oncogenic Activities of v-Src Are Mediated by Multiple Signaling Pathways. Ras AS AN ESSENTIAL MEDIATOR FOR CELL SURVIVAL
J. Biol. Chem.,
July 28, 2000;
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[Abstract]
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S. Priel-Halachmi, I. Ben-Dor, S. Shpungin, T. Tennenbaum, H. Molavani, M. Bachrach, S. Salzberg, and U. Nir
FER Kinase Activation of Stat3 Is Determined by the N-terminal Sequence
J. Biol. Chem.,
September 8, 2000;
275(37):
28902 - 28910.
[Abstract]
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I. C. Gaemers, H. L. Vos, H. H. Volders, S. W. van der Valk, and J. Hilkens
A STAT-responsive Element in the Promoter of the Episialin/MUC1 Gene Is Involved in Its Overexpression in Carcinoma Cells
J. Biol. Chem.,
February 23, 2001;
276(9):
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[Abstract]
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K. Ariyoshi, T. Nosaka, K. Yamada, M. Onishi, Y. Oka, A. Miyajima, and T. Kitamura
Constitutive Activation of STAT5 by a Point Mutation in the SH2 Domain
J. Biol. Chem.,
August 4, 2000;
275(32):
24407 - 24413.
[Abstract]
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