The tal gene was identified upon analysis of t(1;14)(p32;q11), a chromosome translocation observed in the malignant cells of about 2% of patients with T cell acute lymphoblastic leukemia (T-ALL). As a consequence of the translocation, tal is transposed from its normal position on chromosome 1 into the T cell receptor alpha/delta chain gene on chromosome 14. In order to account for its unique association with T-ALL, it has been proposed that the t(1;14)(p32;q11) translocation serves to alter the expression of tal in a manner that promotes leukemic development. Although t(1;14)(p32;q11) is a rare marker of T-ALL, local rearrangements of the tal gene can be observed in about 25% of T-ALL patients. Hence, alteration of tal is a prominent factor in the development of T-ALL. The broad objectives of this project are to determine how alterations of the tal gene affect its expression, and, in turn, how they promote the formation of T-ALL. Accordingly, the specific aims are to define the normal structure and patterns of expression of the tal gene, and to contrast these with the structure and expression of tal genes altered during the development of T-ALL. Potential interactions between tal gene products and other proteins implicated in T-ALL will be examined. Moreover, the malignant potential of the tal gene will be investigated in experimental systems.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA046593-04
Application #
3189906
Study Section
Pathology B Study Section (PTHB)
Project Start
1988-02-01
Project End
1996-01-31
Budget Start
1991-02-01
Budget End
1992-01-31
Support Year
4
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Type
Schools of Medicine
DUNS #
City
Dallas
State
TX
Country
United States
Zip Code
75390
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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