LACK OF RECIPROCAL TRANSLOCATION IN BCR-ABL POSITIVE PH-NEGATIVE CHRONIC MYELOID-LEUKEMIA

We used fluorescence in site hybridization (FISH) to metaphase chromos omes with BCR and ABL cosmid probes in conjunction with the polymerase chain reaction(PCR) to study the mechanism by which the ABL proto-onc ogene is inserted intoa morphologically normal chromosome 22 in patien ts with Ph-negative chronic myeloid leukaemia characterized by the BCR -ABL chimeric gene. In control patients with Ph-positive CML the ABL p robe localized to 22q- and the 3' BCR probe localized to 9q+. In nine Ph-negative CML patients the ABL probe localized to one normal chromos ome 9 and to one 'normal' chromosome 22. Both 5' and 3' BCR probes loc alized exclusively to the chromosomes 22. By PCR all had evidence of B CR-ABL transcripts, but none had evidence of the reciprocal ABL-BCR ge ne product that is seen in 70% of the Ph-positive CML patients. These data confirm the view that Ph-negative CML results from insertion of A BL-containing DNA sequences into a normal-appearing chromosome 22 with out reciprocal translocation ofsequences from chromosome 22 to chromos ome 9.