Clinical Cancer Research Infection and Cancer: Biology, Therapeutics, and Prevention
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sun, L.
Right arrow Articles by Uckun, F. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sun, L.
Right arrow Articles by Uckun, F. M.
Clinical Cancer Research Vol. 5, 2112-2120, August 1999
© 1999 American Association for Cancer Research

Molecular Oncology, Markers, Clinical Correlates

Expression of Dominant-Negative Ikaros Isoforms in T-Cell Acute Lymphoblastic Leukemia1

Lei Sun, Mya-Lisa Crotty, Martha Sensel, Harland Sather, Christopher Navara, James Nachman, Peter G. Steinherz, Paul S. Gaynon, Nita Seibel, Chen Mao, Alexei Vassilev, Gregory H. Reaman and Fatih M. Uckun2

Parker Hughes Cancer Center and Children’s Cancer Group ALL Biology Reference Laboratory, Hughes Institute, St. Paul, Minnesota 55113 [L. S., M-L. C., C. N., A. V., C. M., F. M. U.]; Group Operations Center, Children’s Cancer Group, Arcadia, California 91066 [H. S., M. S.]; Department of Pediatrics, University of Chicago, Chicago, Illinois 60601 [J. N.]; Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021 [P. G. S.]; Department of Hematology-Oncology, Children’s Hospital Los Angeles, Los Angeles, California 90027 [P. S. G.]; and Children’s National Medical Center and the George Washington University, Washington, D.C. 20010 [N. S., G. H. R.]

Ikaros, a zinc finger-containing DNA-binding protein, is required for normal lymphocyte development. Germ-line mutant mice that express only non-DNA binding dominant-negative "leukemogenic" Ikaros isoforms lacking critical NH2-terminal zinc fingers develop an aggressive form of T-cell leukemia. We studied Ikaros gene expression in leukemic cells from 18 children with T-cell acute lymphoblastic leukemia (T-ALL). In each of the 18 T-ALL cases as well as JK-E6–1 and MOLT-3 cell lines, we found high-level expression of dominant-negative isoforms of Ikaros with abnormal subcellular compartmentalization patterns. Nuclear extracts from these cells failed to bind to the IKAROS-specific binding sequence in DNA. PCR cloning and sequencing confirmed that JK-E6–1 and MOLT-3 cell lines as well as leukemic cells from 9 of 10 patients with T-ALL expressed dominant-negative Ikaros isoforms Ik-4, Ik-7, and Ik-8 that lack critical NH2-terminal zinc fingers. In 6 of 10 patients, we detected a specific mutation leading to an in-frame deletion of 10 amino acids ({Delta} KSSMPQKFLG) upstream to the transcription activation domain and adjacent to the COOH-terminal zinc fingers of Ik-2, Ik-4, Ik-7, and Ik-8. Thus, children with T-ALL express high levels of dysfunctional dominant-negative Ikaros isoforms.




This article has been cited by other articles:


Home page
 Cancer Res.Home page
S. Loeper, S. L. Asa, and S. Ezzat
Ikaros Modulates Cholesterol Uptake: A Link between Tumor Suppression and Differentiation
Cancer Res., May 15, 2008; 68(10): 3715 - 3723.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
T. Ronni, K. J. Payne, S. Ho, M. N. Bradley, G. Dorsam, and S. Dovat
Human Ikaros Function in Activated T Cells Is Regulated by Coordinated Expression of Its Largest Isoforms
J. Biol. Chem., January 26, 2007; 282(4): 2538 - 2547.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
V. M. Sharma, J. A. Calvo, K. M. Draheim, L. A. Cunningham, N. Hermance, L. Beverly, V. Krishnamoorthy, M. Bhasin, A. J. Capobianco, and M. A. Kelliher
Notch1 Contributes to Mouse T-Cell Leukemia by Directly Inducing the Expression of c-myc
Mol. Cell. Biol., November 1, 2006; 26(21): 8022 - 8031.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
M. Liu, Y. Ge, S. G. Payton, A. Aboukameel, S. Buck, R. M. Flatley, C. Haska, R. Mohammad, J. W. Taub, and L. H. Matherly
Transcriptional Regulation of the Human Reduced Folate Carrier in Childhood Acute Lymphoblastic Leukemia Cells
Clin. Cancer Res., January 15, 2006; 12(2): 608 - 616.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
A. Dumortier, R. Jeannet, P. Kirstetter, E. Kleinmann, M. Sellars, N. R. dos Santos, C. Thibault, J. Barths, J. Ghysdael, J. A. Punt, et al.
Notch Activation Is an Early and Critical Event during T-Cell Leukemogenesis in Ikaros-Deficient Mice
Mol. Cell. Biol., January 1, 2006; 26(1): 209 - 220.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
E. Smith and M. Sigvardsson
The roles of transcription factors in B lymphocyte commitment, development, and transformation
J. Leukoc. Biol., June 1, 2004; 75(6): 973 - 981.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
B. J. Westman, J. Perdomo, M. Sunde, M. Crossley, and J. P. Mackay
The C-terminal Domain of Eos Forms a High Order Complex in Solution
J. Biol. Chem., October 24, 2003; 278(43): 42419 - 42426.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
K. J. Payne, G. Huang, E. Sahakian, J. Y. Zhu, N. S. Barteneva, L. W. Barsky, M. A. Payne, and G. M. Crooks
Ikaros Isoform X Is Selectively Expressed in Myeloid Differentiation
J. Immunol., March 15, 2003; 170(6): 3091 - 3098.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
F. Ishimaru, T. Yagi, S. Hibi, M. Takanashi, G. Kano, Y. Tabata, T. Imamura, T. Inaba, A. Morimoto, S. Todo, et al.
Expression of Ikaros isoforms in patients with acute myeloid leukemia
Blood, July 30, 2002; 100(4): 1511 - 1513.
[Full Text] [PDF]

Home page
 BloodHome page
T. Yagi, S. Hibi, M. Takanashi, G. Kano, Y. Tabata, T. Imamura, T. Inaba, A. Morimoto, S. Todo, and S. Imashuku
High frequency of Ikaros isoform 6 expression in acute myelomonocytic and monocytic leukemias: implications for up-regulation of the antiapoptotic protein Bcl-XL in leukemogenesis
Blood, February 15, 2002; 99(4): 1350 - 1355.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
C. Tonnelle, F. Bardin, C. Maroc, A.-M. Imbert, F. Campa, A. Dalloul, C. Schmitt, and C. Chabannon
Forced expression of the Ikaros 6 isoform in human placental blood CD34+ cells impairs their ability to differentiate toward the B-lymphoid lineage
Blood, November 1, 2001; 98(9): 2673 - 2680.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
K. J. Payne, J.-H. Nicolas, J. Y. Zhu, L. W. Barsky, and G. M. Crooks
Cutting Edge: Predominant Expression of a Novel Ikaros Isoform in Normal Human Hemopoiesis
J. Immunol., August 15, 2001; 167(4): 1867 - 1870.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
I. Christopherson, M. Piechoki, G. Liu, S. Ratner, and A. Galy
Regulation of L-selectin expression by a dominant negative Ikaros protein
J. Leukoc. Biol., April 1, 2001; 69(4): 675 - 683.
[Abstract] [Full Text]

Home page
 Cancer Res.Home page
K. Nakase, F. Ishimaru, N. Avitahl, H. Dansako, K. Matsuo, K. Fujii, N. Sezaki, H. Nakayama, T. Yano, S. Fukuda, et al.
Dominant Negative Isoform of the Ikaros Gene in Patients with Adult B-Cell Acute Lymphoblastic Leukemia
Cancer Res., August 1, 2000; 60(15): 4062 - 4065.
[Abstract] [Full Text]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 1999 by the American Association for Cancer Research.