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Rearrangement of ALL1 (MLL) in Acute Myeloid Leukemia with Normal Cytogenetics^{1 ,2}

Division of Medicine [M. A. C., M. P. S., D. L., M. R. B., F. Y., K. M., A. R. O., G. M., G. P. H., C. D. B.] and the Departments of Molecular Immunology [M. A. C., M. P. S.] and Pathology [A. W. B.], Roswell Park Cancer Institute, Buffalo, New York 14263; Cancer and Leukemia Group B. Chicago, Illinois, 60004 [M. A. C., D. L., D. C. A., M. R. B., P. N. R., B. L. P., C. A. S., C. D. B.]; and Departments of Medical Genetics [S. K., A. d. l. C.] and Medicine [E. E., T. R.], University of Helsinki, FIN-00014, Helsinki, Finland

Approximately 45% of adults with acute myeloid leukemia (AML) have normal 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 in several such cases of AML, yet its frequency and clinical significance are unclear. We performed Southern analysis of the ALL1 gene in pretreatment samples from 98 AML patients with normal cytogenetics. Eleven of 98 such patients (11%; 95% confidence interval, 6–19%) showed rearrangement of ALL1 at diagnosis. The partial tandem duplication of ALL1 was responsible for ALL1 rearrangement in all such cases examined, making it a frequent molecular defect in adult AML patients with normal cytogenetics. Furthermore, patients with ALL1 rearrangement had a significantly shorter duration of complete remission when compared to patients without ALL1 rearrangement (P = 0.01; median, 7.1 versus 23.2 months). This defect defines for the first time a subset of AML patients with normal cytogenetics who have short durations of complete remission and thus require new therapeutic approaches.

¹ Supported by Grants CA-37027, a Translational Research Grant from The Leukemia Society of America, The Lady Tata Memorial Trust, The Cancer Society of Finland, and The Coleman Leukemia Research Fund.

² The following Cancer and Leukemia Group B institutions, principal investigators, and cytogeneticists participated in this study: University of Alabama, Birmingham, Alabama (Robert Diasio and Andrew Carrol); Bowman Gray Medical Center, Winston-Salem, North Carolina (M. Robert Cooper and Mark J. Pettenati); Dana-Farber Cancer Institute, Boston, Massachusetts (George Canellos and Ramana Tantravahi); Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire (L. Herbert Maurer and T. K. Mohandas); Duke University, Durham, North Carolina (Jeffrey Crawford and Mazin Qumsiyeh); Long Island Jewish Medical Center, New Hyde Park, New York (Marc Citron and Prasad R. K. Koduru); Eastern Maine Medical Center, Portland, Maine (Thomas Ervin and Laurent Beauregard); University of Maryland Cancer Center, Baltimore, Maryland (Ernest Borden and Judith Stamberg); University of Minnesota, Minneapolis, Minnesota (Bruce Peterson and Diane Arthur); University of Missouri, Columbia, Missouri (Michael Perry and Tim Huang, Grant CA12046); Mt. Sinai School of Medicine, New York, New York (James F. Holland and Vesna Najfeld); New York Hospital-Cornell Medical Center, New York, New York (Ted Szatrowski and R. Verma); University of North Carolina, Chapel Hill, North Carolina (Thomas Shea and Kathleen W. Rao); North Shore University Hospital, Manhasset, New York (Daniel R. Budman and Prasad Koduru, Grant CA35279); Rhode Island Hospital, Providence, Rhode Island (Louis Leone and Hon Fong Louie Mark); Roswell Park Cancer Institute, Buffalo, New York (Ellis Levine and AnneMarie Block); State University of New York Health Science Center at Syracuse, Syracuse, New York (Stephan Graziano and Constance K. Stein); University of California, San Diego, California (Mark Green and Renee Bernstein); University of Massachusetts Medical Center (F. Stephen Seagren and Philip Townes); University of Tennessee, Memphis, Tennessee (Alvin Mauer and Sugandhi A. Tharapel); and Walter Reed Army Medical Center, Washington, District of Columbia (Nancy Dawson and Ratwal B. Surana).

³ To whom requests for reprints should be addressed, at Division of Hematology-Oncology, Comprehensive Cancer Center, Ohio State University, 320 West 10th Avenue, Columbus, OH 43210.

⁴ Present address: Division of Hematology-Oncology, Comprehensive Cancer Center, Ohio State University, 320 West 10th Avenue, Columbus, OH 43210.

Received 7/14/97. Accepted 10/27/97.

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