3?BCR recombines withIGL locus inBCR-ABL-positive Philadelphia-negative chronic myeloid leukemia

Abstract

We have isolated the 3′ BCR breakpoint junction of a complex BCR‐ABL1 rearrangement found in leukemic cells with a cytogenetically normal karyotype, and the corresponding germline fragment that spanned the 3′ BCR recombination site. Fluorescence in situ hybridization localized the 3′ BCR recombination site to 22q11, about 350–600 kb proximal to BCR. Restriction map and DNA sequence comparisons indicated that 3′ M‐Bcr had recombined at a site within the variable region (Itv Region IV) of the immunoglobulin lambda (IGL) locus. Somatic rearrangement of DNA sequences (variable, joining, and constant regions) within the IGL locus, as in other Ig and TCR loci, represents the basis for human antibody diversity. Misrecombination of these somatically rearranging sites has been associated with chromosomal rearrangements in lymphoid leukemia and lymphoma, but there are no previous descriptions of IGL involvement in genomic aberrations associated with myeloid leukemia. Genes Chromosomes Cancer 26:366–371, 1999. © 1999 Wiley‐Liss, Inc.