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Previous Volume 329:909-914 September 23, 1993 Number 13 Next

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ABSTRACT

Background Translocations involving chromosome band 11q23 are very frequent in both acute lymphoblastic and acute myeloid leukemias and are the most common genetic alteration in infants with leukemia. In all age groups and all phenotypes of leukemia, an 11q23 translocation carries a poor prognosis. A major question has been whether one or several genes on band 11q23 are implicated in these leukemias. Previously, we identified the chromosomal breakpoint region in leukemias with the common 11q23 translocations and subsequently cloned a gene named MLL that spans the 11q23 breakpoint.

Methods We isolated a 0.74-kb BamHI fragment from a complementary DNA (cDNA) clone of the MLL gene. To determine the incidence of MLL rearrangements in patients with 11q23 abnormalities, we analyzed DNA from 61 patients with acute leukemia, 3 cell lines derived from such patients, and 20 patients with non-Hodgkin's lymphoma and 11q23 aberrations.

Results The 0.74-kb cDNA probe detected DNA rearrangements in the MLL gene in 58 of the patients with leukemia, in the 3 cell lines, and in 3 of the patients with lymphoma. All the breaks occurred in an 8.3-kb breakpoint cluster region within the MLL gene. The probe identified DNA rearrangements in all 48 patients with the five common 11q23 translocations involving chromosomes 4, 6, 9, and 19, as well as in 16 patients with uncommon 11q23 aberrations. Twenty-one different chromosomal breakpoints involving the MLL gene were detected.

Conclusions MLL gene rearrangements were detected with a single probe and a single restriction-enzyme digest in all DNA samples from patients with the common 11q23 translocations as well as in 16 patients or cell lines with other 11q23 anomalies. The ability to detect an MLL gene rearrangement rapidly and reliably, especially in patients with limited material for cytogenetic analysis, should make it possible to identify patients who have a poor prognosis and therefore require aggressive chemotherapy or marrow transplantation.

Source Information

From the Section of Hematology and Oncology, Departments of Medicine (M.J.T., R.C.B., D.M., H.K., R.A.L., M.M.L., M.O.D., J.D.R.), Molecular Genetics and Cell Biology (H.J.G., S.Z.P., J.D.R.), and Pediatrics (N.R.M.), University of Chicago, Chicago; the Saitama Cancer Center, Saitama, Japan (Y.K.); Southwest Biomedical Research Institute and Genetrix, Inc., Scottsdale, Ariz. (R.M., A.A.S.); and Memorial Sloan-Kettering Cancer Center, New York (R.S.K.C.).Presented in part at the annual meeting of the American Society of Hematology, Anaheim, Calif., December 4-8, 1992.

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