In the great majority of patients with chronic myelogenous leukemia (CML) the 
reciprocal translocation between chromosomes 9 and 22, t(9;22)(q34;q11), 
resulting in the Philadelphia (Ph) chromosome produces fusion DNA sequences 
consisting of the 5' part of the major breakpoint cluster region-1 (M-BCR-1) and 
the ABL protooncogene which encodes for the P210BCR-ABL phosphoprotein with 
tyrosine kinase activity implicated in the pathogenesis of CML. Molecular 
analysis was performed on 25 patients with Ph-positive CML using 2 breakpoint 
cluster region (bcr) probes within the M-BCR-1 DNA sequences, and two of them 
did not contain either detectable rearranged DNA homologous to the 5' side bcr 
probe or ABL-related fusion mRNA. The chromosomal in situ hybridization 
technique revealed that these two Ph-positive CML cases did not carry DNAs 
homologous to the 5' bcr or ABL probes on the Ph chromosome. Furthermore, one of 
the two Ph-positive CML cases did not show either rearranged DNA or regions 
homologous to the 3' bcr probe on a 9q+ chromosome, while the other CML case 
showed a rearrangement detected by the 3' bcr probe and transposition of the 3' 
bcr homologous to the 9q+ chromosome. Thus, the possibility is raised that the 
BCR/ABL fusion DNA has been deleted in rare CML cases, and that the deletion 
possibly occurred in a stepwise manner following the formation of the Ph 
chromosome at any stage of the disease.