CD34: structure, biology, and clinical utility [see comments]

Krause, DS; Fackler, MJ; Civin, CI; May, Win

doi:10.1182/blood.v87.1.1.1

Cited by 756 publications

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“…CD34 þ cells do not contain lymphocytes but do include most haemopoietic progenitor and stem cells. CD34 þ cell populations purified from BM cells or peripheral blood MNC preparations have been clinically used for BM transplantation and in gene therapy trials (Krause et al, 1996). Although a battery of growth factors has been extensively used to induce growth and differentiation of BM progenitor cells, studies of the pathophysiology of BM failure syndromes suggest that inhibitory cytokines may have profound effects on the behaviour of these cells in vivo and in vitro.…”

Section: Discussionmentioning

confidence: 99%

Expression and modulation of cellular receptors for interferon‐γ, tumour necrosis factor, and Fas on human bone marrow CD34⁺ cells

et al. 1997

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Summary.Interferon-g (IFN-g), tumour necrosis factor-a (TNF-a) and Fas-ligand can mediate potent inhibitory signals in haemopoietic cells. Clinical and laboratory studies have suggested the involvement of these cytokines in the regulation of normal haemopoiesis and in the pathophysiology of bone marrow (BM) failure syndromes. As the effects of cytokines may also be regulated at the cellular receptor level, we studied the expression and modulation of TNF receptor (TNFR), IFN-gR and Fas-R on haemopoietic progenitor cells. In freshly isolated BM, using flow cytometry, TNFR1 (p55), TNFR2 (p75), IFN-gR, and Fas-R were detected on 5-12% of mononuclear cells. Two-colour staining showed comparable receptor expression on a CD34 þ population, which includes haemopoietic progenitor and stem cells. Using reverse transcriptase-PCR (RT-PCR) transcription of mRNA coding for these receptors was demonstrated in fresh, highly purified CD34 þ cells. These findings indicate that the effects of these factors on progenitor cells may be directly mediated. In cultured BM cells, expression of TNFR1 was not influenced by IFN-g, TNF-a or apoptosis-inducing anti-Fas monoclonal antibody (mAb). IFN-g decreased CD34 þ cell TNFR2 expression. CD34 þ cell Fas-R expression was increased by IFN-g and TNF-a. IFN-gR expression was enhanced by antiFas mAb and to lesser degree with TNF-a. Similar results were obtained with RT-PCR analysis in cultured CD34 þ cells. Potentiation of anti-Fas mAb-mediated inhibition of haemopoietic colony formation by IFN-g and TNF-a was observed. Similarly, anti-Fas mAb enhanced the inhibitory effects of IFN-g. These results suggest that, in addition to interacting at the level of intracellular signalling pathways, IFN-g, TNF-a or Fas-ligand may potentiate or antagonize their effects through modulation of cytokine receptor expression.

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Section: Discussionmentioning

confidence: 99%

Expression and modulation of cellular receptors for interferon‐γ, tumour necrosis factor, and Fas on human bone marrow CD34⁺ cells

et al. 1997

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“…The heavily glycosylated cell surface molecule gives rise to a number of different epitopes (Watt et al, 1987;. The expression of these epitopes may be related to function and/or maturation (Egeland & Gaudernack, 1994b;Majdic et al, 1994;Greaves et al, 1995;Krause et al, 1996). The presence or absence of different glycosylation-related epitopes is therefore of interest for the study of haemopoiesis and for immunophenotyping and positive selection of CD34 cells.…”

Section: Discussionmentioning

confidence: 99%

Differences in the distribution of CD34 epitopes on normal haemopoietic progenitor cells and leukaemic blast cells

et al. 1996

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The CD34 molecule expressed on haemopoietic progenitor cells contains a large number of epitopes whose expression may be related to the maturation or function of the cells. Monoclonal antibodies specific for different epitopes have been reported to detect different numbers of CD34+ leukaemic blast cells. We wanted to confirm this observation and study whether parallel findings could be observed for normal haemopoietic progenitor cells. The cells were immunophenotyped by flow cytometry with a series of monoclonal antibodies reactive with different CD34 epitopes. Class III epitopes (resistant to enzymatic cleavage with neuraminidase, chymopapain and a glycoprotease from Pasteurella haemolytica) showed a broader distribution on normal haemopoietic progenitor cells and leukaemic blast cells than class I epitopes (sensitive to cleavage with all three enzymes) and class II epitopes (sensitive to degradation with glycoprotease and chymopapain, and resistant to neuraminidase). The subpopulation of normal progenitor cells which exclusively expressed class III epitopes had flow cytometric characteristics compatible with mature myeloid progenitor cells whereas class I, II and III epitopes were equally expressed on cells enriched for immature subsets. No discordant epitope expression could be observed for the more immature leukaemias (AML-M0/1) and a higher percentage of the more mature leukaemic blast cells (AML-M3 and AML-M4/5) expressed class III epitopes compared to the percentage expressing class I and II epitopes. These data indicate that CD34 class III epitopes are more broadly distributed on normal haemopoietic progenitor cells and leukaemic blast cells than class I and II epitopes, and that class I and II epitopes may be down-regulated prior to class III epitopes during normal haemopoietic progenitor cell differentiation. These findings should be considered when selecting CD34 mabs for quantification and positive selection of haemopoietic progenitor cells for research and clinical purposes.

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“…The CD34 antigen (Ag) is a phosphoglycoprotein that is expressed on the cell membrane of human haematopoietic progenitor cells in bone marrow (BM), peripheral blood (PB) and cord blood (CB) (reviewed in Krause et al, 1996). Animal models (Berenson et al, 1988) and clinical transplantation studies using highly enriched cell populations have also demonstrated the capacity of CD34 + cells to behave as true stem cells, as they engraft in lethally irradiated allogeneic hosts (Bensinger et al, 1996).…”

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Functional and kinetic characterization of granulocyte colony‐stimulating factor‐primed CD34⁻ human stem cells

et al. 2003

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Summary.We assessed the functional properties and the kinetic status in vitro, and the engraftment potential in vivo of human haematopoietic stem cells according to the expression of CD34 antigen. Lin ) CD34 ) and Lin ) CD34 + cells were isolated from granulocyte colony-stimulating factor-primed peripheral blood (PB) cells of healthy donors. The CD34 ) cell fraction did not contain either clonogenic cells in semisolid culture or long-term culture initiating cells (LTC-IC). However, stroma-dependent liquid cultures and cytokines induced CD34 expression on a minority of stem cells, acquisition of clonogenic capacity and generation of LTC-IC. Significantly higher percentages of quiescent G 0 cells and lower percentages of cycling G 1 cells were found in Lin ) CD34 ) cells when compared with Lin ) CD34 + cells. Kinetic quiescence of Lin ) CD34 ) cells was associated with a significantly higher expression of the negative regulators of the cell cycle, p27 Kip1 and p21 cip1/waf1 . Cytokine-mediated induction of CD34, in vitro, resulted in cycling of stem cells and downregulation of p27. There was a higher rate of human long-term engraftment in immunocompromised non-obese diabetic (NOD)/recombination activating gene 1 null and NOD/severe combined immunodeficient-b 2 microglobulin null mice injected with CD34 + cells. Thus, our study indicated that CD34 expression on human PB stem cells was associated with haematopoietic activity, cell-cycle recruitment and downregulation of p27 Kip1 in vitro and higher engraftment capacity in vivo.

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CD34: structure, biology, and clinical utility [see comments]

Cited by 756 publications

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Expression and modulation of cellular receptors for interferon‐γ, tumour necrosis factor, and Fas on human bone marrow CD34⁺ cells

Expression and modulation of cellular receptors for interferon‐γ, tumour necrosis factor, and Fas on human bone marrow CD34⁺ cells

Differences in the distribution of CD34 epitopes on normal haemopoietic progenitor cells and leukaemic blast cells

Functional and kinetic characterization of granulocyte colony‐stimulating factor‐primed CD34⁻ human stem cells

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CD34: structure, biology, and clinical utility [see comments]

Cited by 756 publications

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Expression and modulation of cellular receptors for interferon‐γ, tumour necrosis factor, and Fas on human bone marrow CD34+ cells

Expression and modulation of cellular receptors for interferon‐γ, tumour necrosis factor, and Fas on human bone marrow CD34+ cells

Differences in the distribution of CD34 epitopes on normal haemopoietic progenitor cells and leukaemic blast cells

Functional and kinetic characterization of granulocyte colony‐stimulating factor‐primed CD34− human stem cells

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Expression and modulation of cellular receptors for interferon‐γ, tumour necrosis factor, and Fas on human bone marrow CD34⁺ cells

Expression and modulation of cellular receptors for interferon‐γ, tumour necrosis factor, and Fas on human bone marrow CD34⁺ cells

Functional and kinetic characterization of granulocyte colony‐stimulating factor‐primed CD34⁻ human stem cells