ALTERNATIVE RNA SPLICING OF THE MLL GENE IN NORMAL AND MALIGNANT-CELLS

The human MLL(mixed-lineage leukemia or myeloid-lymphoid leukemia) gen e belongs to the trithorax gene family of which the Drosophila trithor ax (trx) gene is known to regulate homeotic genes through alternative RNA splicing. To test if such a splicing mechanism also operates in ML L, we evaluated mRNA transcripts from a large number of normal and mal ignant human cells, making use of RT-PCR, PCR cloning, DNA sequencing and Northern blot analysis. Our findings indicate that different cell types transcribe MLL mRNA species lacking exons that generally encode putative regulatory domains such as AT hooks (exon 3), repression doma in (exon 6), zinc finger motifs (exon 8) and activation domain (exon 1 8). Such findings suggest that posttranscriptional regulation by alter native RNA splicing may play an important role in MLL gene expression and provides the rationale for a mechanism by which this gene, with mu ltiple functional domains, could produce discrete protein products tha t may prove critical in the regulation of human homeobox genes.