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Human CD34(+) and CD34(+)CD38(-) hematopoietic progenitors in sickle cell disease differ phenotypically and functionally from normal and suggest distinct subpopulations that generate F cells.
Exp Hematol. 2004 May; 32(5):483-93.EH

Abstract

OBJECTIVE

Sickle cell disease (SCD) is remarkable for stress erythropoiesis. We investigated the progenitor populations contributing to erythroid stress.

MATERIALS AND METHODS

We characterized hematopoietic progenitor cells in sickle bone marrow and sickle peripheral blood from patients with SCD compared to those in normal bone marrow.

RESULTS

There were increased proportions of sickle bone marrow and sickle peripheral blood CD34(+) cells that coexpressed glycophorin A (GlyA), normally expressed late during erythroid differentiation when CD34 is down-regulated. Remarkably, increased numbers of CD34(+)CD38(-) hematopoietic progenitor cells from sickle bone marrow (p < 0.03) and sickle peripheral blood (p < 0.004) coexpressed GlyA, compared to normal bone marrow CD34(+)CD38(-) hematopoietic progenitor cells. At a molecular level, even the sickle bone marrow and sickle peripheral blood CD34(+)CD38(-) hematopoietic progenitor cells not expressing GlyA by fluorescence-activated cell sorting or reverse transcriptase-polymerase chain reaction expressed the erythroid-specific gene GATA-1, unlike normal bone marrow, suggesting desynchronized erythroid gene expression in the SCD hematopoietic progenitor cells. We also generated red blood cells in vitro from GlyA(+) and GlyA(-)CD34(+) cells. GlyA(+)CD34(+) produced more F cells (p < 0.02) and had lower clonogenicity (p < 0.01) and erythroid expansion potential. Increased F cells were generated only from sickle CD34(+) hematopoietic progenitor cells (p < 0.04), as occurs in vivo.

CONCLUSION

Stress erythropoiesis in SCD has been postulated to accelerate erythropoiesis and production of F cells. Thus, CD34(+)CD38(-) expressing GlyA may represent the "stress progenitor" population. This is the first study characterizing CD34(+) and CD34(+)CD38(-) hematopoietic progenitor cells in sickle bone marrow, comparing them to sickle peripheral blood and normal bone marrow and using them to generate sickle red blood cells that recapitulate F cell production observed in vivo. We identified a unique population of GlyA(+)CD34(+) cells in SCD, which is in an accelerated erythroid differentiation pathway, has not down-regulated CD34 antigen expression, and predominantly generates F cells.

Authors+Show Affiliations

Division of Hematology-Oncology, Childrens Hospital Los Angeles, Los Angeles, CA 90027, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15145217

Citation

Luck, Lori, et al. "Human CD34(+) and CD34(+)CD38(-) Hematopoietic Progenitors in Sickle Cell Disease Differ Phenotypically and Functionally From Normal and Suggest Distinct Subpopulations That Generate F Cells." Experimental Hematology, vol. 32, no. 5, 2004, pp. 483-93.
Luck L, Zeng L, Hiti AL, et al. Human CD34(+) and CD34(+)CD38(-) hematopoietic progenitors in sickle cell disease differ phenotypically and functionally from normal and suggest distinct subpopulations that generate F cells. Exp Hematol. 2004;32(5):483-93.
Luck, L., Zeng, L., Hiti, A. L., Weinberg, K. I., & Malik, P. (2004). Human CD34(+) and CD34(+)CD38(-) hematopoietic progenitors in sickle cell disease differ phenotypically and functionally from normal and suggest distinct subpopulations that generate F cells. Experimental Hematology, 32(5), 483-93.
Luck L, et al. Human CD34(+) and CD34(+)CD38(-) Hematopoietic Progenitors in Sickle Cell Disease Differ Phenotypically and Functionally From Normal and Suggest Distinct Subpopulations That Generate F Cells. Exp Hematol. 2004;32(5):483-93. PubMed PMID: 15145217.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Human CD34(+) and CD34(+)CD38(-) hematopoietic progenitors in sickle cell disease differ phenotypically and functionally from normal and suggest distinct subpopulations that generate F cells. AU - Luck,Lori, AU - Zeng,Licheng, AU - Hiti,Alan L, AU - Weinberg,Kenneth I, AU - Malik,Punam, PY - 2003/09/19/received PY - 2004/01/12/revised PY - 2004/01/23/accepted PY - 2004/5/18/pubmed PY - 2004/6/25/medline PY - 2004/5/18/entrez SP - 483 EP - 93 JF - Experimental hematology JO - Exp Hematol VL - 32 IS - 5 N2 - OBJECTIVE: Sickle cell disease (SCD) is remarkable for stress erythropoiesis. We investigated the progenitor populations contributing to erythroid stress. MATERIALS AND METHODS: We characterized hematopoietic progenitor cells in sickle bone marrow and sickle peripheral blood from patients with SCD compared to those in normal bone marrow. RESULTS: There were increased proportions of sickle bone marrow and sickle peripheral blood CD34(+) cells that coexpressed glycophorin A (GlyA), normally expressed late during erythroid differentiation when CD34 is down-regulated. Remarkably, increased numbers of CD34(+)CD38(-) hematopoietic progenitor cells from sickle bone marrow (p < 0.03) and sickle peripheral blood (p < 0.004) coexpressed GlyA, compared to normal bone marrow CD34(+)CD38(-) hematopoietic progenitor cells. At a molecular level, even the sickle bone marrow and sickle peripheral blood CD34(+)CD38(-) hematopoietic progenitor cells not expressing GlyA by fluorescence-activated cell sorting or reverse transcriptase-polymerase chain reaction expressed the erythroid-specific gene GATA-1, unlike normal bone marrow, suggesting desynchronized erythroid gene expression in the SCD hematopoietic progenitor cells. We also generated red blood cells in vitro from GlyA(+) and GlyA(-)CD34(+) cells. GlyA(+)CD34(+) produced more F cells (p < 0.02) and had lower clonogenicity (p < 0.01) and erythroid expansion potential. Increased F cells were generated only from sickle CD34(+) hematopoietic progenitor cells (p < 0.04), as occurs in vivo. CONCLUSION: Stress erythropoiesis in SCD has been postulated to accelerate erythropoiesis and production of F cells. Thus, CD34(+)CD38(-) expressing GlyA may represent the "stress progenitor" population. This is the first study characterizing CD34(+) and CD34(+)CD38(-) hematopoietic progenitor cells in sickle bone marrow, comparing them to sickle peripheral blood and normal bone marrow and using them to generate sickle red blood cells that recapitulate F cell production observed in vivo. We identified a unique population of GlyA(+)CD34(+) cells in SCD, which is in an accelerated erythroid differentiation pathway, has not down-regulated CD34 antigen expression, and predominantly generates F cells. SN - 0301-472X UR - https://www.unboundmedicine.com/medline/citation/15145217/Human_CD34_+__and_CD34_+_CD38____hematopoietic_progenitors_in_sickle_cell_disease_differ_phenotypically_and_functionally_from_normal_and_suggest_distinct_subpopulations_that_generate_F_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0301472X04000438 DB - PRIME DP - Unbound Medicine ER -