Abstract

The goals of this research program are to identify the genetic lesions responsible for T-ALL and to determine how these defects promote leukemogenesis. Tumor-specific activation of the TAL1 gene is the most common genetic lesion associated with T-ALL. Therefore, to understand the role of TAL1 in the pathogenesis of T-ALL, the following specific aims will be pursued. First, the functional properties of TAL1 polypeptides will be examined by characterizing the cellular proteins that associate with them during normal (i.e., erythroid) and neoplastic (T-ALL) development. Second, the malignant potential of TAL1 will be explored by targeted expression of TAL1 transgenes in the T cell compartment of mice. Finally, an attempt will be made to identify novel TAL1-related genes that may also play a role in the formation of T-ALL.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA046593-14
Application #
6172202
Study Section
Special Emphasis Panel (ZRG2-MEP (01))
Program Officer
Mufson, R Allan
Project Start
1999-09-30
Project End
2002-04-30
Budget Start
2000-05-01
Budget End
2002-04-30
Support Year
14
Fiscal Year
2000
Total Cost
$376,742
Indirect Cost

  Institution

Name
Columbia University (N.Y.)
Department
Pathology
Type
Schools of Medicine
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032

  Publications

Bucher, K; Sofroniew, M V; Pannell, R et al. (2000) The T cell oncogene Tal2 is necessary for normal development of the mouse brain. Dev Biol 227:533-44
Baer, R; Hwang, L Y; Bash, R O (1997) Transcription factors of the bHLH and LIM families: synergistic mediators of T cell acute leukemia? Curr Top Microbiol Immunol 220:55-65
Larson, R C; Lavenir, I; Larson, T A et al. (1996) Protein dimerization between Lmo2 (Rbtn2) and Tal1 alters thymocyte development and potentiates T cell tumorigenesis in transgenic mice. EMBO J 15:1021-7
Hwang, L Y; Baer, R J (1995) The role of chromosome translocations in T cell acute leukemia. Curr Opin Immunol 7:659-64
Bash, R O; Hall, S; Timmons, C F et al. (1995) Does activation of the TAL1 gene occur in a majority of patients with T-cell acute lymphoblastic leukemia? A pediatric oncology group study. Blood 86:666-76
Wadman, I; Li, J; Bash, R O et al. (1994) Specific in vivo association between the bHLH and LIM proteins implicated in human T cell leukemia. EMBO J 13:4831-9
Hsu, H L; Wadman, I; Tsan, J T et al. (1994) Positive and negative transcriptional control by the TAL1 helix-loop-helix protein. Proc Natl Acad Sci U S A 91:5947-51
Valge-Archer, V E; Osada, H; Warren, A J et al. (1994) The LIM protein RBTN2 and the basic helix-loop-helix protein TAL1 are present in a complex in erythroid cells. Proc Natl Acad Sci U S A 91:8617-21
Brown, L; Baer, R (1994) HEN1 encodes a 20-kilodalton phosphoprotein that binds an extended E-box motif as a homodimer. Mol Cell Biol 14:1245-55
Hsu, H L; Wadman, I; Baer, R (1994) Formation of in vivo complexes between the TAL1 and E2A polypeptides of leukemic T cells. Proc Natl Acad Sci U S A 91:3181-5

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