GENOMIC DIVERSITY CORRELATES WITH CLINICAL VARIATION IN PH'-NEGATIVE CHRONIC MYELOID-LEUKEMIA

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)1,2. This translocation relocates the proto-oncogene c-abl, normally found on chromosome 9q34, to within the breakpoint cluster region (bcr) on chromosome 22qll (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 transcript9,10 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 precisely12. 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. © 1986 Nature Publishing Group.