Expression of a distinctive BCR-ABL oncogene in Ph1-positive Acute Lymphocytic Leukemia (ALL)

Steven S. Clark, Jami Mclaughlin, Michael Timmons, Ann Marie Pendergast, Yinon Ben-Neriah, Lois W. Dow, William Crist, Giovanni Rovera, Stephen D. Smith, Owen N. Witte*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

222 Scopus citations

Abstract

The Philadelphia chromosome (Ph1) 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 P210BCR-ABL tyrosine kinase. The Ph1 chromosome in ALL expresses a distinct ABL-derived 7-kilobase messenger RNA that encodes the P185ALL-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 P185ALL-ABL. Both P210 BCR-ABL and P185ALL-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 P210BCR-ABL but not P185ALL-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 Ph 1-positive ALL cells. In Ph1-positive ALL, ABL sequences were joined to BCR sequences approximately 1.5 kilobases 5′ of the CML junction. P185ALL-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.

Original languageAmerican English
Pages (from-to)775-777
Number of pages3
JournalScience
Volume239
Issue number4841
DOIs
StatePublished - 1988

Fingerprint

Dive into the research topics of 'Expression of a distinctive BCR-ABL oncogene in Ph1-positive Acute Lymphocytic Leukemia (ALL)'. Together they form a unique fingerprint.

Cite this