RT-PCR Analysis of Breakpoints Involving the MLL Gene Located at 11q23 in Acute Leukemia.

Chromosome rearrangements of chromosome 11 at band 1 1q23 are detected in a high proportion of infant leukemias (<l yr) as well as childhood and adult acute leukemlas of both myelold and lymphold types. Molecular and cytogenetic analysis of these tumors has shown that 7-10% of acute lymphoblastic, and 5-6% of acute nonlymphocytic leukemias are involved in this way (1). Leukemias with rearrangements of band 1lq23 typically are CD l0, exhibit blphenotypic or mixed-lineage phenotype, and have a poor response to chemotherapy (2). The gene on chromosome 11 involved in the 1 lq23 rearrangement has been cloned recently (3, 4) and characterized. It is known as MLL (or ALL-1, HRX, HTRX), the gene encodes a 3969-amino acid polypeptide showing areas of homology to the Drosophila trithorax gene, a putative regulator of homeotic genes in segment determination (5). The MLL gene is large and complex, containing two DNA-binding domains consisting of three AT-hook motifs and two multiple zinc-finger domains, and thus has the characteristics of a transcription factor likely to be involved in the regulation of gene expression.