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Presence of Cell Lineage-specific Hypomethylated Sites in the Major Breakpoint Cluster Region

Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, Minnesota 55455

To examine the role of DNA methylation in breakpoint location of chromosomal translocation, HpaII sites in and flanking the M-bcr on chromosome 22 were mapped in DNA from blood granulocytes and lymphocytes, bone marrow cells, thymic tissue, and spermatozoa from normal individuals. Allelic HpaII sites were identified clustered in a 600-base pair genomic area of the M-bcr. Bone marrow cells and blood granulocyte DNA showed identical allelic patterns. Thymic tissue and blood lymphocytes showed identical allelic patterns distinct from bone marrow cells and blood granulocytes. Spermatozoa showed a third methylation pattern. In all individuals, the HpaII sites were present within the BamHI/BglII fragment of the M-bcr, the same area associated with high breakpoint frequency in chronic myelogenous leukemia (CML). Three of 15 patients with chronic phase CML showed fully methylated rearranged BglII/BglII M-bcr restriction fragments not seen in normal bone marrow cells. These methylation patterns of the M-bcr may be important in CML breakpoint location and may be a marker for tissue differentiation.

¹ To whom requests for reprints should be addressed, at Department of Laboratory Medicine and Pathology, Mayo Building, Box 198, University of Minnesota Hospitals, 420 Delaware St. S.E., Minneapolis, MN 55455.

Received 2/20/90. Revised 5/ 2/90.