title: Genomic diversity correlates with clinical variation in Ph'-negative chronic myeloid leukaemia.
abstract: The Philadelphia chromosome (Ph') is found in the blood cells of about 90% of patients with chronic myeloid leukaemia (CML) and usually results from the reciprocal chromosome translocation t(9;22). This translocation relocates the proto-oncogene c-abl, normally found on chromosome 9q34, to within the breakpoint cluster region (bcr) on chromosome 22q11 (refs 3-8). The juxtaposition of c-abl and the 5' portion of bcr appears to be the critical genomic event in CML and results in a novel 8-kilobase (kb) fused abl/bcr transcript and a c-abl-related protein of relative molecular mass 210,000 (ref.11). About 10% of adult patients diagnosed as CML lack the Ph' chromosome; they represent a heterogeneous group of disorders which are difficult to diagnose precisely. We have examined five patients with CML whose leukaemic cells have a normal karyotype. We report here that two of the patients showed the same genomic change as occurs in Ph'-positive CML, but the change resulted from a mechanism other than chromosomal translocation. The remaining three patients showed no genomic rearrangement. This genomic diversity correlated with the clinical differences between the patients.
mesh_terms: D000328:Adult; D000368:Aged; D002904:Chromosomes, Human, 21-22 and Y; D002906:Chromosomes, Human, 6-12 and X; D004247:DNA / Q000235:genetics; D004262:DNA Restriction Enzymes; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000503:physiopathology; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D009857:Oncogenes; D000090063:Proto-Oncogene Mas; D014178:Translocation, Genetic
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D004247:DNA; D004262:DNA Restriction Enzymes