Expression of a distinctive BCR-ABL oncogene in Ph1
-positive acute lymphocytic leukemia (ALL)
The Philadelphia chromosome (Ph1) is a translocation between chromosomes 9 and 22 that is found in chronic myelogenous leukemia (CML) and a subset of acute lymphocytic leukemia patients (ALL). In CML, this results in the expression of a chimeric 8.5-kilobase BCR-ABL transcript that encodes the P210(BCR-ABL) tyrosine kinase. The Ph1 chromosome in ALL expresses a distinct ABL-derived 7-kilobase messenger RNA that encodes the P185(ALL-ABL) protein. Since the expression of different oncogene products may play a role in the distinctive presentation of Ph1-positive ALL versus CML, it is necessary to understand the molecular basis for the expression of P185(ALL-ABL). Both P210(BCR-ABL) and P185(ALL-ABL) are recognized by an antiserum directed to BCR determinants in the amino-terminal region of both proteins. Antisera to BCR determinants proximal to the BCR-ABL junction in CML immunoprecipitated P210(BCR-ABL) but not P185(ALL-ABL). Nucleotide sequence analysis of complementary DNA clones made from RNA from the Ph1-positive ALL SUP-B15 cell line, and S1 nuclease protection analysis confirmed the presence of BCR-ABL chimeric transcripts in PH1-positive ALL cells. In Ph1-positive ALL, ABL sequences were joined to BCR sequences approximately 1.5 kilobases 5' of the CML junction. P185(ALL-ABL) represents the product of a BCR-ABL fusion gene in Ph1-positive ALL that is distinct from the BCR-ABL fusion gene of CML.