THE STRUCTURE OF THE HUMAN ALL-1 MLL HRX GENE

The human ALL-1/MLL/HRX gene on chromosome 11q23 is the site of many l ocally clustered chromosomal alterations associated with several types of acute leukemias, including deletions, partial duplications and rec iprocal translocations. Structurally variant proteins derived from an altered ALL-1 gene presumably make essential contributions to the mali gnant transformation of hematopoietic progenitor cells. The ALL-1 gene is spread over approximately 92 kb and consists of at least 37 exons. An exon/intron map including the position of the 3'-end of the gene a nd a detailed restriction map were produced and an updated map is pres ented. Data from other laboratories were incorporated where compatible . Exon/intron boundaries were sequenced and an intron-phase analysis w as per-formed. The results are expected to contribute to a better unde rstanding of those structural alterations of the gene that conserve th e open reading frame and produce presumably oncogenic variants of the ALL-1 protein. They will also facilitate the rapid molecular diagnosis of structural alterations of this gene and the choice of therapeutic options. Mechanisms that may potentially account for the striking clus tering of the translocation breakpoints in the breakpoint cluster regi on of the gene are discussed.