Expression of a distinctive BCR-ABL oncogene in Ph 1 -positive Acute Lymphocytic Leukemia (ALL)


Journal Article

The Philadelphia chromosome (Ph 1 ) is a translocation between chromosomes 9 and 22 that is found in chrome 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 Ph 1 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 Ph 1 -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 Ph 1 -positive ALL SUP-B15 cell line, and S1 nuclease protection analysis confirmed the presence of BCR-ABL chimeric transcripts in Ph 1 -positive ALL cells. In Ph 1 -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 Ph 1 -positive ALL that is distinct from the BCR-ABL fusion gene of CML.

Full Text

Duke Authors

Cited Authors

  • Clark, SS; Mclaughlin, J; Timmons, M; Pendergast, AM; Ben-Neriah, Y; Dow, LW; Crist, W; Rovera, G; Smith, SD; Witte, ON

Published Date

  • January 1, 1988

Published In

Volume / Issue

  • 239 / 4841

Start / End Page

  • 775 - 777

International Standard Serial Number (ISSN)

  • 0036-8075

Digital Object Identifier (DOI)

  • 10.1126/science.3422516

Citation Source

  • Scopus