Autologous lymphocytes inhibit hemopoiesis in long-term culture in patients with myelodysplastic syndrome.

2.50
Hdl Handle:
http://hdl.handle.net/10541/81293
Title:
Autologous lymphocytes inhibit hemopoiesis in long-term culture in patients with myelodysplastic syndrome.
Authors:
Baumann, Irith; Scheid, Christof; Koref, Mauro Santibanez; Swindell, Ric; Stern, Peter L; Testa, Nydia G
Abstract:
OBJECTIVE: The current therapy of myelodysplastic syndrome (MDS) is unsatisfactory and comprises mainly supportive treatment or antileukemic chemotherapy. Recent studies about successful immunosuppressive therapy suggest an autoimmune mechanism in subtypes of myelodysplastic syndrome. PATIENTS AND METHODS: To investigate this hypothesis, bone marrow mononuclear cells (MNC) from 15 patients with low-grade MDS, refractory anemia, and refractory anemia with ringed sideroblasts (RA and RARS), and from 7 normal donors were depleted of CD2(+), CD5(+), and CD7(+) lymphocytes using magnetic cell sorting. Depleted and nondepleted MNC were seeded onto irradiated allogeneic bone marrow stroma and the generation of colony-forming-cells (CFC), the clonal origin of hemopoietic progenitor cells in long-term bone marrow culture (LTC), was compared. RESULTS: The capacity of MNC from 7 healthy donors to generate hemopoiesis remained unchanged in the lymphocyte-depleted LTC. In contrast, cultures initiated with lymphocyte-depleted MNC from patients with RA and RARS exhibited a significantly increased generation of CFC compared with the corresponding nondepleted cultures. Microsatellite analysis in 6 patients revealed that a significantly increased number of CFC grown in lymphocyte-depleted LTC showed no allelic loss, suggesting an outgrowth of normal hemopoietic cells. CONCLUSION: These results provide a rationale for the recently described successful treatment of MDS with immunosuppressive therapy. We suggest that in certain subtypes of MDS the residual normal hemopoiesis is suppressed by autoimmune mechanisms, eventually allowing the expansion of the abnormal clone.
Affiliation:
Department of Experimental Haematology, Christie Hospital NHS Trust, Manchester, England, UK. irith.baumann@patho.imed.uni-erlangen.de
Citation:
Autologous lymphocytes inhibit hemopoiesis in long-term culture in patients with myelodysplastic syndrome. 2002, 30 (12):1405-11 Exp. Hematol.
Journal:
Experimental Hematology
Issue Date:
Dec-2002
URI:
http://hdl.handle.net/10541/81293
PubMed ID:
12482502
Type:
Article
Language:
en
ISSN:
0301-472X
Appears in Collections:
All Christie Publications ; All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorBaumann, Irith-
dc.contributor.authorScheid, Christof-
dc.contributor.authorKoref, Mauro Santibanez-
dc.contributor.authorSwindell, Ric-
dc.contributor.authorStern, Peter L-
dc.contributor.authorTesta, Nydia G-
dc.date.accessioned2009-09-16T13:31:34Z-
dc.date.available2009-09-16T13:31:34Z-
dc.date.issued2002-12-
dc.identifier.citationAutologous lymphocytes inhibit hemopoiesis in long-term culture in patients with myelodysplastic syndrome. 2002, 30 (12):1405-11 Exp. Hematol.en
dc.identifier.issn0301-472X-
dc.identifier.pmid12482502-
dc.identifier.urihttp://hdl.handle.net/10541/81293-
dc.description.abstractOBJECTIVE: The current therapy of myelodysplastic syndrome (MDS) is unsatisfactory and comprises mainly supportive treatment or antileukemic chemotherapy. Recent studies about successful immunosuppressive therapy suggest an autoimmune mechanism in subtypes of myelodysplastic syndrome. PATIENTS AND METHODS: To investigate this hypothesis, bone marrow mononuclear cells (MNC) from 15 patients with low-grade MDS, refractory anemia, and refractory anemia with ringed sideroblasts (RA and RARS), and from 7 normal donors were depleted of CD2(+), CD5(+), and CD7(+) lymphocytes using magnetic cell sorting. Depleted and nondepleted MNC were seeded onto irradiated allogeneic bone marrow stroma and the generation of colony-forming-cells (CFC), the clonal origin of hemopoietic progenitor cells in long-term bone marrow culture (LTC), was compared. RESULTS: The capacity of MNC from 7 healthy donors to generate hemopoiesis remained unchanged in the lymphocyte-depleted LTC. In contrast, cultures initiated with lymphocyte-depleted MNC from patients with RA and RARS exhibited a significantly increased generation of CFC compared with the corresponding nondepleted cultures. Microsatellite analysis in 6 patients revealed that a significantly increased number of CFC grown in lymphocyte-depleted LTC showed no allelic loss, suggesting an outgrowth of normal hemopoietic cells. CONCLUSION: These results provide a rationale for the recently described successful treatment of MDS with immunosuppressive therapy. We suggest that in certain subtypes of MDS the residual normal hemopoiesis is suppressed by autoimmune mechanisms, eventually allowing the expansion of the abnormal clone.en
dc.language.isoenen
dc.subjectRefractory Anaemiaen
dc.subjectHaematopoiesisen
dc.subjectHaematopoietic Stem Cellsen
dc.subject.meshAdolescent-
dc.subject.meshAdult-
dc.subject.meshAged-
dc.subject.meshAged, 80 and over-
dc.subject.meshAnemia, Refractory-
dc.subject.meshBone Marrow-
dc.subject.meshCase-Control Studies-
dc.subject.meshChild-
dc.subject.meshClone Cells-
dc.subject.meshCoculture Techniques-
dc.subject.meshHematopoiesis-
dc.subject.meshHematopoietic Stem Cells-
dc.subject.meshHumans-
dc.subject.meshImmunophenotyping-
dc.subject.meshLeukocytes, Mononuclear-
dc.subject.meshLoss of Heterozygosity-
dc.subject.meshLymphocyte Depletion-
dc.subject.meshLymphocyte Subsets-
dc.subject.meshMiddle Aged-
dc.subject.meshMyelodysplastic Syndromes-
dc.subject.meshStromal Cells-
dc.titleAutologous lymphocytes inhibit hemopoiesis in long-term culture in patients with myelodysplastic syndrome.en
dc.typeArticleen
dc.contributor.departmentDepartment of Experimental Haematology, Christie Hospital NHS Trust, Manchester, England, UK. irith.baumann@patho.imed.uni-erlangen.deen
dc.identifier.journalExperimental Hematologyen

Related articles on PubMed

All Items in Christie are protected by copyright, with all rights reserved, unless otherwise indicated.