Biological effects of stroma-derived factor-1 alpha on normal and CML CD34+ haemopoietic cells.

2.50
Hdl Handle:
http://hdl.handle.net/10541/90132
Title:
Biological effects of stroma-derived factor-1 alpha on normal and CML CD34+ haemopoietic cells.
Authors:
Dürig, J; Rosenthal, C; Elmaagacli, A; Heyworth, Clare M; Halfmeyer, K; Kasper, Christoph; Novotny, J; Dührsen, U
Abstract:
We compared the biological effects of the CXC chemokine SDF-1alpha on immunomagnetically purified CD34+ cells isolated from human normal bone marrow (NBM), leukapheresis products (LP) and patients with chronic myeloid leukaemia (CML). LP CD34+ cells showed a significantly stronger migration response to SDF-1alpha (100 ng/ml) than CD34+ cells isolated from the peripheral blood (PB) of CML patients (P < 0.05). The chemotactic response to SDF-1alpha was also reduced in CML BM CD34+ cells in comparison to NBM CD34+ cells but the observed differences were not statistically significant. In analogy to normal CD34+ cells circulating CML PB CD34+ cells were less responsive to SDF-1alpha than their BM counterparts (P < 0.05). Furthermore, SDF-1alpha elicited similar concentration-dependent growth suppressive effects on normal and CML CD34+ cells (P > 0.05) in colony-forming cell assays. We then demonstrated that SDF-1alpha triggers intracellular calcium increases in CD34+ cells and there were no differences in the time course and dose response characteristics of normal and CML CD34+ cells. The reduced migration response to SDF-1alpha in CML CD34+ cells was not due to a down-regulation of the SDF-1alpha receptor CXCR-4 as flow cytometric analysis revealed similar CXCR-4 expression levels on NBM, LP, CML PB and CML BM CD34+ cells (P > 0.05). Finally, no differences in the modulation of CXCR-4 levels in response to SDF-1alpha and serum were observed in CML and normal CD34+ cells. Our data suggest that the impaired chemotactic response of CML CD34+ cells to SDF-1alpha is not caused by a lack or complete uncoupling of CXCR-4, but may be due to an intracellular signalling defect downstream of the receptor.
Affiliation:
Department of Haematology, University Hospital Essen, Germany.
Citation:
Biological effects of stroma-derived factor-1 alpha on normal and CML CD34+ haemopoietic cells. 2000, 14 (9):1652-60 Leukemia
Journal:
Leukemia
Issue Date:
Sep-2000
URI:
http://hdl.handle.net/10541/90132
PubMed ID:
10995013
Type:
Article
Language:
en
ISSN:
0887-6924
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorDürig, Jen
dc.contributor.authorRosenthal, Cen
dc.contributor.authorElmaagacli, Aen
dc.contributor.authorHeyworth, Clare Men
dc.contributor.authorHalfmeyer, Ken
dc.contributor.authorKasper, Christophen
dc.contributor.authorNovotny, Jen
dc.contributor.authorDührsen, Uen
dc.date.accessioned2010-01-20T15:09:05Z-
dc.date.available2010-01-20T15:09:05Z-
dc.date.issued2000-09-
dc.identifier.citationBiological effects of stroma-derived factor-1 alpha on normal and CML CD34+ haemopoietic cells. 2000, 14 (9):1652-60 Leukemiaen
dc.identifier.issn0887-6924-
dc.identifier.pmid10995013-
dc.identifier.urihttp://hdl.handle.net/10541/90132-
dc.description.abstractWe compared the biological effects of the CXC chemokine SDF-1alpha on immunomagnetically purified CD34+ cells isolated from human normal bone marrow (NBM), leukapheresis products (LP) and patients with chronic myeloid leukaemia (CML). LP CD34+ cells showed a significantly stronger migration response to SDF-1alpha (100 ng/ml) than CD34+ cells isolated from the peripheral blood (PB) of CML patients (P < 0.05). The chemotactic response to SDF-1alpha was also reduced in CML BM CD34+ cells in comparison to NBM CD34+ cells but the observed differences were not statistically significant. In analogy to normal CD34+ cells circulating CML PB CD34+ cells were less responsive to SDF-1alpha than their BM counterparts (P < 0.05). Furthermore, SDF-1alpha elicited similar concentration-dependent growth suppressive effects on normal and CML CD34+ cells (P > 0.05) in colony-forming cell assays. We then demonstrated that SDF-1alpha triggers intracellular calcium increases in CD34+ cells and there were no differences in the time course and dose response characteristics of normal and CML CD34+ cells. The reduced migration response to SDF-1alpha in CML CD34+ cells was not due to a down-regulation of the SDF-1alpha receptor CXCR-4 as flow cytometric analysis revealed similar CXCR-4 expression levels on NBM, LP, CML PB and CML BM CD34+ cells (P > 0.05). Finally, no differences in the modulation of CXCR-4 levels in response to SDF-1alpha and serum were observed in CML and normal CD34+ cells. Our data suggest that the impaired chemotactic response of CML CD34+ cells to SDF-1alpha is not caused by a lack or complete uncoupling of CXCR-4, but may be due to an intracellular signalling defect downstream of the receptor.en
dc.language.isoenen
dc.subjectHaematopoietic Stem Cellsen
dc.subjectLeukaemiaen
dc.subjectTumour Stem Cell Assayen
dc.subject.meshAntigens, CD19-
dc.subject.meshAntigens, CD34-
dc.subject.meshB-Lymphocytes-
dc.subject.meshCalcium-
dc.subject.meshCell Movement-
dc.subject.meshChemokine CXCL12-
dc.subject.meshChemokines, CXC-
dc.subject.meshChemotactic Factors-
dc.subject.meshFusion Proteins, bcr-abl-
dc.subject.meshHematopoietic Stem Cells-
dc.subject.meshHumans-
dc.subject.meshLeukapheresis-
dc.subject.meshLeukemia, Myelogenous, Chronic, BCR-ABL Positive-
dc.subject.meshNeprilysin-
dc.subject.meshReceptors, CXCR4-
dc.subject.meshStem Cells-
dc.subject.meshTumor Stem Cell Assay-
dc.subject.meshUp-Regulation-
dc.titleBiological effects of stroma-derived factor-1 alpha on normal and CML CD34+ haemopoietic cells.en
dc.typeArticleen
dc.contributor.departmentDepartment of Haematology, University Hospital Essen, Germany.en
dc.identifier.journalLeukemiaen

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