BCR-ABL protein expression in peripheral blood cells of chronic myelogenous leukemia patients undergoing therapy.
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.
Guo
J Q
JQ
Department of Biology, University of California at San Diego, La Jolla.
Lian
J Y
JY
Xian
Y M
YM
Lee
M S
MS
Deisseroth
A B
AB
Stass
S A
SA
Champlin
R E
RE
Talpaz
M
M
Wang
J Y
JY
Arlinghaus
R B
RB
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
D016044:Fusion Proteins, bcr-abl