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


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.


CONCLUSIONS
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.
Baumann
Irith
I
Department of Experimental Haematology, Christie Hospital NHS Trust, Manchester, England, UK. irith.baumann@patho.imed.uni-erlangen.de
Scheid
Christof
C
Koref
Mauro Santibanez
MS
Swindell
Richard
R
Stern
Peter
P
Testa
Nydia G
NG
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000753:Anemia, Refractory / Q000209:etiology / Q000276:immunology / Q000473:pathology; D001853:Bone Marrow / Q000473:pathology; D016022:Case-Control Studies; D002648:Child; D002999:Clone Cells / Q000473:pathology; D018920:Coculture Techniques; D006410:Hematopoiesis / Q000276:immunology*; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D016130:Immunophenotyping; D007963:Leukocytes, Mononuclear / Q000473:pathology; D019656:Loss of Heterozygosity; D008212:Lymphocyte Depletion; D016131:Lymphocyte Subsets / Q000276:immunology / Q000473:pathology*; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D017154:Stromal Cells / Q000166:cytology