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The Partial Nontandem Duplication of the MLL (ALL1) Gene Is a Novel Rearrangement That Generates Three Distinct Fusion Transcripts in B-Cell Acute Lymphoblastic Leukemia¹

Divisions of Hematology and Oncology [S. P. W., G. M., M. A. C.] and Human Cancer Genetics [M. P. S., A. G. F., M. A. C.], Department of Pathology [L. L. C., K. S. T.] and Comprehensive Cancer Center [K. M., C. D. B., M. A. C.], The Ohio State University, Columbus, Ohio 43210; Department of Medicine [N. J. Z.], Loyola University of Chicago, Cardinal Bernadin Cancer Center, Maywood, Illinois 60153; and TVWT Institute for Child Health Research [U. R. K.], University of Western Australia, Perth, Western Australia 6008

A partial nontandem duplication (PNTD) of mixed lineage leukemia (MLL) gene is described in B-cell acute lymphoid leukemia without structural cytogenetic abnormalities at 11q23 and 9p22. A duplicated portion of MLL is interrupted by the insertion of a region of 9p22 that includes the 3'-end of the AF9 gene. The PNTD encodes: (a) a PNTD transcript; (b) a partial tandem duplication of MLL; and (c) a chimeric transcript fusing MLL to the 3'-end of AF9, mimicking the t(9;11)(p22;q23) and expressed 1024-fold higher than the other two. The MLL PNTD, therefore, contributes toward leukemogenesis through simultaneous production of fusion transcripts that are otherwise encoded by three distinct genetic defects.

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