Philadelphia chromosome-positive chronic myelogenous leukemia with deleted fusion of BCR and ABL genes.

Abstract

ABSTRACTIn 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.