Increased Erythropoietin-Receptor Expression on CD34-Positive Bone Marrow Cells From Patients With Chronic Myeloid Leukemia

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-phyco- erythrin, and bio...

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Bibliographic Details
Published in:Blood 1992-02, Vol.79 (3), p.642-649
Main Authors: Wognum, Albertus W., Krystal, Gerald, Eaves, Connie J., Eaves, Allen C., Lansdorp, Peter M.
Format: Article
Language:English
Subjects:
Antigens, CD - analysis
Antigens, CD34
Biological and medical sciences
Bone Marrow - immunology
Bone Marrow - metabolism
Cell Separation
Flow Cytometry
Hematologic and hematopoietic diseases
Hematology
Humans
Leukemia, Myelogenous, Chronic, BCR-ABL Positive - metabolism
Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
Life Sciences & Biomedicine
Medical sciences
Receptors, Cell Surface - metabolism
Receptors, Erythropoietin
Receptors, Transferrin - metabolism
Science & Technology
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Summary: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-phyco- erythrin, 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 glycoph-orin-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 pheno- type 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.© 1992 by The American Society of Hematology. 0006-4971/92/7903-0003$3.00/0
ISSN:0006-4971
1528-0020
DOI:10.1182/blood.V79.3.642.642