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Evidence for downregulation of erythropoietin receptor in bone marrow erythroid cells of patients with chronic idiopathic neutropenia.
Exp Hematol. 2006 Oct; 34(10):1312-22.EH

Abstract

OBJECTIVE

The aim of this study is to probe the mechanisms underlying anemia in patients with chronic idiopathic neutropenia (CIN) by evaluating parameters of bone marrow (BM) erythropoiesis.

PATIENTS AND METHODS

Ten CIN patients fulfilling the criteria of anemia of chronic disease, 27 nonanemic CIN patients, and 30 healthy volunteers were enrolled in the study. Reserves and survival characteristics of BM erythroid cells were evaluated using flow cytometry and clonogenic assays. Serum erythropoietin (EPO) was measured with ELISA. Expression of EPO receptors (EPORs) on BM erythroid cells was evaluated by flow cytometry and reverse-transcription polymerase chain reaction.

RESULTS

CIN patients display defective erythropoiesis in addition to previously reported impaired granulopoiesis. Patients have low number of CD34(+)/CD71(+) progenitor and CD36(-)/ Glycophorin A(+) (GlycoA(+)) precursor BM cells, and increased proportion of apoptotic cells within the CD34(+)/CD71(+) and CD36(+)/GlycoA(+) compartments. Burst-forming units erythroid (BFU-Es) in BM mononuclear or purified CD34(+) cells were significantly reduced in the patients. Patient BFU-Es increased significantly following in vitro treatment with tumor necrosis factor-alpha (TNF-alpha) and/or interferon gamma (IFN-gamma)-neutralizing antibodies. Local TNF-alpha and IFN-gamma production was higher in anemic than in nonanemic patients. EPO production was appropriate in the patients, but EPOR expression was significantly reduced in patient GlycoA(+) cells, especially in anemic patients.

CONCLUSION

Impaired BM erythropoiesis in CIN patients is probably the result of increased local production of TNF-alpha and IFN-gamma that induce apoptosis, cell growth inhibition, and downregulation of EPOR expression on erythroid cells. We suggest that anemia in CIN patients displays overlapping pathophysiologic features with anemia of chronic disease.

Authors+Show Affiliations

Department of Hematology of the University of Crete School of Medicine, Heraklion, Crete, Greece.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Comparative Study
Journal Article

Language

eng

PubMed ID

16982324

Citation

Pontikoglou, Charalampos, et al. "Evidence for Downregulation of Erythropoietin Receptor in Bone Marrow Erythroid Cells of Patients With Chronic Idiopathic Neutropenia." Experimental Hematology, vol. 34, no. 10, 2006, pp. 1312-22.
Pontikoglou C, Liapakis G, Pyrovolaki K, et al. Evidence for downregulation of erythropoietin receptor in bone marrow erythroid cells of patients with chronic idiopathic neutropenia. Exp Hematol. 2006;34(10):1312-22.
Pontikoglou, C., Liapakis, G., Pyrovolaki, K., Papadakis, M., Bux, J., Eliopoulos, G. D., & Papadaki, H. A. (2006). Evidence for downregulation of erythropoietin receptor in bone marrow erythroid cells of patients with chronic idiopathic neutropenia. Experimental Hematology, 34(10), 1312-22.
Pontikoglou C, et al. Evidence for Downregulation of Erythropoietin Receptor in Bone Marrow Erythroid Cells of Patients With Chronic Idiopathic Neutropenia. Exp Hematol. 2006;34(10):1312-22. PubMed PMID: 16982324.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evidence for downregulation of erythropoietin receptor in bone marrow erythroid cells of patients with chronic idiopathic neutropenia. AU - Pontikoglou,Charalampos, AU - Liapakis,George, AU - Pyrovolaki,Katerina, AU - Papadakis,Marios, AU - Bux,Juergen, AU - Eliopoulos,George D, AU - Papadaki,Helen A, PY - 2005/12/22/received PY - 2006/05/12/revised PY - 2006/05/12/accepted PY - 2006/9/20/pubmed PY - 2006/11/15/medline PY - 2006/9/20/entrez SP - 1312 EP - 22 JF - Experimental hematology JO - Exp Hematol VL - 34 IS - 10 N2 - OBJECTIVE: The aim of this study is to probe the mechanisms underlying anemia in patients with chronic idiopathic neutropenia (CIN) by evaluating parameters of bone marrow (BM) erythropoiesis. PATIENTS AND METHODS: Ten CIN patients fulfilling the criteria of anemia of chronic disease, 27 nonanemic CIN patients, and 30 healthy volunteers were enrolled in the study. Reserves and survival characteristics of BM erythroid cells were evaluated using flow cytometry and clonogenic assays. Serum erythropoietin (EPO) was measured with ELISA. Expression of EPO receptors (EPORs) on BM erythroid cells was evaluated by flow cytometry and reverse-transcription polymerase chain reaction. RESULTS: CIN patients display defective erythropoiesis in addition to previously reported impaired granulopoiesis. Patients have low number of CD34(+)/CD71(+) progenitor and CD36(-)/ Glycophorin A(+) (GlycoA(+)) precursor BM cells, and increased proportion of apoptotic cells within the CD34(+)/CD71(+) and CD36(+)/GlycoA(+) compartments. Burst-forming units erythroid (BFU-Es) in BM mononuclear or purified CD34(+) cells were significantly reduced in the patients. Patient BFU-Es increased significantly following in vitro treatment with tumor necrosis factor-alpha (TNF-alpha) and/or interferon gamma (IFN-gamma)-neutralizing antibodies. Local TNF-alpha and IFN-gamma production was higher in anemic than in nonanemic patients. EPO production was appropriate in the patients, but EPOR expression was significantly reduced in patient GlycoA(+) cells, especially in anemic patients. CONCLUSION: Impaired BM erythropoiesis in CIN patients is probably the result of increased local production of TNF-alpha and IFN-gamma that induce apoptosis, cell growth inhibition, and downregulation of EPOR expression on erythroid cells. We suggest that anemia in CIN patients displays overlapping pathophysiologic features with anemia of chronic disease. SN - 0301-472X UR - https://www.unboundmedicine.com/medline/citation/16982324/Evidence_for_downregulation_of_erythropoietin_receptor_in_bone_marrow_erythroid_cells_of_patients_with_chronic_idiopathic_neutropenia_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0301-472X(06)00327-4 DB - PRIME DP - Unbound Medicine ER -