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

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    Authors
    Baumann, Irith
    Scheid, Christof
    Koref, Mauro Santibanez
    Swindell, Ric
    Stern, Peter L
    Testa, Nydia G
    Affiliation
    Department of Experimental Haematology, Christie Hospital NHS Trust, Manchester, England, UK. irith.baumann@patho.imed.uni-erlangen.de
    Issue Date
    2002-12
    
    Metadata
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    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.
    Citation
    Autologous lymphocytes inhibit hemopoiesis in long-term culture in patients with myelodysplastic syndrome. 2002, 30 (12):1405-11 Exp. Hematol.
    Journal
    Experimental Hematology
    URI
    http://hdl.handle.net/10541/81293
    PubMed ID
    12482502
    Type
    Article
    Language
    en
    ISSN
    0301-472X
    Collections
    All Christie Publications
    All Paterson Institute for Cancer Research

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