BCR-ABL protein expression in peripheral blood cells of chronic myelogenous
leukemia patients undergoing therapy
JQ Guo, JY Lian, YM Xian, MS Lee, AB Deisseroth, SA Stass, RE Champlin, M Talpaz, JY Wang and RB Arlinghaus
Department of Biology, University of California at San Diego, La Jolla.
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.
Volume 83,
Issue 12,
pp. 3629-3637,
06/15/1994
Copyright © 1994 by The American Society of Hematology