MLL TANDEM DUPLICATION AND MULTIPLE SPLICING IN ADULT ACUTE MYELOID-LEUKEMIA WITH NORMAL KARYOTYPE

Rearrangement of the MLL (myeloid-lymphoid or mixed-lineage leukemia) gene through a reciprocal chromosomal translocation is found in 5% of adult acute myeloid (AML) and 10% of pediatric acute lymphoid (ALL) le ukemia. More than 25 different reciprocal chromosomal translocations, with an 11q23 breakpoint, fuse the MLL gene (also named ALL-I, HRX and Htrx1) to a second partner gene. These leukemias have poor prognosis and frequently have a monocytic, lymphoid or biphenotypic (myeloid and lymphoid) antigen expression in blast cells. Approximately 20-30% of patients diagnosed as having adult de novo AML have normal chromosomes by metaphase analysis and the majority of these patients have good pr ognosis. With the use of reverse transcriptase-polymerase chain reacti on (RT-PCR) technique and Southern blot analysis, we found that seven of 34 such patients (21%) had a tandem partial duplication of exons 2 to 6 or 2 to 8 of the MLL gene. These seven patients showed a median s urvival of 2.7 months, compared to a 6.8 months median survival for al l other patients in the study. If confirmed on a large series of patie nts, our findings may help differentiate AML with normal karyotype and poor prognosis from those with normal karyotype and a more favorable prognosis.