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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.
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
html.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.


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