Different patterns of chromosome and molecular breakage in classic Ph¹ chronic myelogenous leukemia (CML) and variant Ph¹ CML

Variant translocations involving either chromosome 9, chromosome 22, or both with other chromosomes have been reported in about 8% of chronic myelogenous leukemia (CML) patients. In the 22 Ph⁺ patients studied in our laboratory, two showed variant translocations: t(9;22;11) (q34;q11;q13), and t(9;11) (q34;q11). We compared the pattern of involvement of different chromosomes (and bands) in secondary structural changes in CMLs carrying the t(9;22) (q34;q11) and in the variant translocations. Analysis showed significant differences in the pattern of involvement of different chromosomes and chromosome sites in the secondary structural changes in classic CMLs. This study, thus identifies nonrandomly involved chromosome sites that may be targeted for detailed molecular analysis to obtain an understanding of their role in disease progression. In the variant translocations chromosomes and chromosome bands were nonrandomly involved. Breakpoint cluster region (bcr) of the BCR gene was found to be rearranged in our two cases. We compared the location of molecular breaks within the bcr in classic and variant translocations. We found that translocation breaks occurred more frequently in the 5' region, and less frequently in the 3' region of bcr in variant translocations as compared with classic translocations. The significance of these findings in the etiology of CML is discussed.