Spectral karyotypic study of the HL-60 cell line: Detection of complex rearrangements involving chromosomes 5, 7, and 16 and delineation of critical region of deletion on 5q31.1

Interstitial deletions of the q arm of chromosome 5 have been associated wi th acute myelogenous leukemia (AML); therefore, accurate identification of rearrangements of this chromosome in a model cell line, HL-60, is important for understanding the critical genes involved in this disease. In this stu dy, we employed a newly developed technology termed spectral karyotyping to delineate chromosomal rearrangements in this cell line. Our study revealed a derivative of chromosome 7 that resulted from translocations of chromoso me arms 5q and 26q to 7q; that is, der(7)t(5;7)(?;q?)t(5;16)(?;q?). Interes tingly, both chromosomes 5 and 7 were also involved in translocations with chromosome 16 in der(16) t(5;16)(q?;q?22 similar to 24) and der(16)t(7;16)( ?;q?22 similar to 24), respectively. Other notable chromosomal abnormalitie s that were not previously reported in the HL-60 included an insertion of c hromosome 8 in the q arm of chromosome 11, a translocation between chromoso mes 9 and 14, and a translocation between chromosomes 14 and 15. In an atte mpt to define the loss of the 5q31.1 region in HL-60, we performed fluoresc ence in situ hybridization analysis by utilizing bacterial artificial chrom osomes BAC1 and BAC2 that spanned the IL9 and EGR1 gene interval, which was previously shown to be a critical region of loss in AML. We showed that a copy of both BAC1 (spanning the D5S399 locus) and BAC2 (spanning the D5S393 locus centromeric to BAC1) were present in the normal chromosome 5,;but a second copy of BAC1 was lost and a second copy of BAC2 was inserted in the der(16)t(7;16) chromosome. Thus, not only was this study the first to use t he new 24-color karyotyping technique to identify several novel chromosomal rearrangements in HL-60, but it also narrowed the 5q31.1 critical region o f deletion to the region represented by BAC1. (C) Elsevier Science Inc., 19 99. All rights reserved.