Role of TCL1 and ALL1 in human leukemias and development.

We have investigated the role of chromosomal translocations in the pathogenesis of human leukemias. The study of T-cell chronic lymphocytic leukemias and T-cell prolymphocytic leukemia has led to the identification of TCL1, a novel gene that is deregulated by translocations, t(14;14)(q11;q32), or inversions, inv(14)(q11;q32.1). Introduction of a human TCL1 gene juxtaposed to the Ick promoter into fertilized mouse eggs resulted in the development of transgenic mice that developed mature T-cell leukemias, indicating that TCL1 is a transforming oncogene. We have also investigated acute leukemias with abnormalities at chromosome 11q23. We have identified a gene, ALL1, that can fuse to many different genes in acute leukemias. We have also shown that ALL1 can fuse with ALL1 in acute myelogenous leukemia. We have proposed that the ALL1 fusion genes may act by a dominant negative mechanism.