title: BCR-ABL protein expression in peripheral blood cells of chronic myelogenous leukemia patients undergoing therapy.
abstract: Chronic myelogenous leukemia (CML) is a myeloproliferative disorder associated with the Philadelphia chromosome (Ph1) in more than 95% of these patients. The Ph1 and the resulting BCR-ABL fused genes are markers for this type of leukemia. In CML, the product of the fused BCR-ABL gene is typically a protein of approximately 2,000 amino acids termed P210 BCR-ABL. We have developed an assay for the BCR-ABL protein involving Western blotting of circulating white blood cells (WBC) with an anti-ABL monoclonal antibody that can detect P210 BCR-ABL and P145 ABL in peripheral blood cells from chronic phase Ph1-positive leukemia patients. This assay was used to analyze the BCR-ABL protein content of circulating WBC from CML patients before and after various treatments. In parallel to changes in percentages of Ph1-positive blood cells as determined by cytogenetic analyses of bone marrow samples, BCR-ABL protein expression in blood cells decreased or increased as patients entered remission or underwent relapse. Of interest, six Ph1-negative CML patients were BCR-ABL protein-positive. All except one had a rearrangement in the major breakpoint cluster region and that patient expressed P185 BCR-ABL and not P210. Our results indicate that the BCR-ABL Western blotting assay has clinical applications for both diagnosis and prospective evaluation of Ph1-positive and Ph1-negative CML patients.
authors.affiliation: Department of Biology, University of California at San Diego, La Jolla.
authors.forename: J Q
authors.initials: JQ
authors.lastname: Guo
authors.forename: J Y
authors.initials: JY
authors.lastname: Lian
authors.forename: Y M
authors.initials: YM
authors.lastname: Xian
authors.forename: M S
authors.initials: MS
authors.lastname: Lee
authors.forename: A B
authors.initials: AB
authors.lastname: Deisseroth
authors.forename: S A
authors.initials: SA
authors.lastname: Stass
authors.forename: R E
authors.initials: RE
authors.lastname: Champlin
authors.forename: M
authors.initials: M
authors.lastname: Talpaz
authors.forename: J Y
authors.initials: JY
authors.lastname: Wang
authors.forename: R B
authors.initials: RB
authors.lastname: Arlinghaus
mesh_terms: D016044:Fusion Proteins, bcr-abl / Q000097:blood*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood* / Q000628:therapy; D007962:Leukocytes / Q000737:chemistry*; D010677:Philadelphia Chromosome; D014407:Tumor Cells, Cultured
chemical_list: D016044:Fusion Proteins, bcr-abl