REARRANGEMENT OF ALL1 (MLL) IN ACUTE MYELOID-LEUKEMIA WITH NORMAL CYTOGENETICS

Approximately 45% of adults with acute myeloid Leukemia (AML) have nor mal cytogenetics and therefore lack structural abnormalities that can assist in the localization and characterization of molecular defects. The partial tandem duplication of the ALL1 (MLL) gene has been found i n several such cases of AML, yet its frequency and clinical significan ce are unclear. We performed Southern analysis of the ALL1 gene in pre treatment samples from 98 AML patients with normal cytogenetics. Eleve n of 98 such patients (11%; 95% confidence interval, 6-19%) showed rea rrangement of ALL1 at diagnosis. The partial tandem duplication of ALL 1 was responsible for ALL1 rearrangement in all such cases examined, m aking it a frequent molecular defect in adult AML patients with normal cytogenetics. Furthermore, patients with ALL1 rearrangement had a sig nificantly shorter duration of complete remission when compared to pat ients without ALL1 rearrangement (P = 0.01; median, 7.1 versus 23.2 mo nths). This defect defines for the first time a subset of AML patients with normal cytogenetics who have short durations of complete remissi on and thus require new therapeutic approaches.