STRUCTURE AND EXPRESSION OF THE HUMAN TRITHORAX-LIKE GENE-1 INVOLVED IN ACUTE LEUKEMIAS

The human trithorax-like gene 1 (Htrx1 gene) is disrupted in 11q23 tra nslocations that are associated with acute leukemias. Sequencing of a partial human cDNA revealed an open reading frame encoding 1012 amino acids with extensive homology to the Drosophila trithorax protein, par ticularly in the zinc finger-like domains. Htrx1 gene appears to be un ique in the human genome and has been conserved during evolution. Use of the human cDNA as a probe demonstrates that this gene is interrupte d in both infant and adult acute myeloid (AML) and lymphoid (ALL) leuk emia patients with 11q23 translocations. The structure of the Htrx1 ge ne around the breakpoints shows that this part of the human gene is in terrupted by nine introns. As a result of the rearrangement, zinc fing er domains are translocated in both ALL and AML patients. Expression s tudies reveal that the Htrx1 gene differentially expresses three trans cripts within the normal lymphocyte cell lineage.