Involvement of a human gene related to the Drosophila spen gene in the recurrent t(1;22) translocation of acute megakaryocytic leukemia

The recurrent t(1;22)(p13;q13) translocation is exclusively associated with infant acute megakaryoblastic leukemia. We have identified the two genes i nvolved in this translocation. Both genes possess related sequences in the Drosophila genome. The chromosome 22 gene (megakaryocytic acute leukemia, M AL) product is predicted to be involved in chromatin organization, and the chromosome 1 gene (one twenty-two. OTT) product is related to the Drosophil a split-end (spen) family of proteins. Drosophila genetic experiments ident ified spen as involved in connecting the Raf and Hox pathways. Because almo st all of the sequences and all of the identified domains of both OTT and M AL proteins are included in the predicted fusion protein, the OTT-MAL fusio n could aberrantly modulate chromatin organization, Hox differentiation pat hways, or extracellular signaling.