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Increased erythropoietin-receptor expression on CD34-positive bone marrow
cells from patients with chronic myeloid leukemia
AW Wognum, G Krystal, CJ Eaves, AC Eaves and PM Lansdorp
Terry Fox Laboratory, B.C. Cancer Agency, Vancouver, Canada.
Erythropoietin-receptor (EpR) expression on bone marrow cells from normal
individuals and from patients with chronic myeloid leukemia (CML) was
examined by multiparameter flow cytometry after stepwise amplified
immunostaining with biotin-labeled Ep, streptavidin- conjugated
R-phycoerythrin, and biotinylated monoclonal anti-R- phycoerythrin. This
approach allowed the detection of EpR-positive cells in all bone marrow
samples studied. Most of the EpR-positive cells in normal bone marrow were
found to be CD45-dull, CD34-negative, transferrin-receptor-positive and
glycophorin-A-intermediate to - positive. This phenotype is characteristic
of relatively mature erythroid precursors, ie, colony-forming
units-erythroid and erythroblasts recognizable by classic staining
procedures. Approximately 5% of normal EpR-positive cells displayed an
intermediate expression of CD45, suggesting that these represented
precursors of the CD45-dull EpR-positive cells. Some EpR-positive cells in
chronic myeloid leukemia (CML) bone marrow had a phenotype similar to the
major EpR-positive phenotype in normal bone marrow, ie, CD34-negative and
CD45-dull. However, there was a disproportionate increase in the relative
number of EpR-positive/CD45-intermediate cells in CML bone marrow. Even
more striking differences between normal individuals and CML patients were
observed when EpR-expression on CD34-positive marrow cells was analyzed.
Very few EpR-positive cells were found in the CD34- positive fraction of
normal bone marrow, whereas a significant fraction of the CD34-positive
marrow cells from five of five CML patients expressed readily detectable
EpR. These findings suggest that control of EpR expression is perturbed in
the neoplastic clone of cells present in patients with CML. This may be
related to the inadequate output of mature red blood cells typical of CML
patients and may also be part of a more generalized perturbation in
expression and/or functional integrity of other growth factor receptors on
CML cells.
Volume 79,
Issue 3,
pp. 642-649,
02/01/1992
Copyright © 1992 by The American Society of Hematology

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