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.
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