Myelodysplastic syndrome (MDS) is believed to be a stem-cell disorder involving 
cytopenia and dysplastic changes in three hematopoietic lineages. However, the 
involvement of pluripotent stem cells and progenitor cells has not been 
clarified conclusively. To address this issue, we used fluorescence in situ 
hybridization (FISH) of blood and bone marrow (BM) smears for mature cells and 
FISH of cells sorted by fluorescence-activated cell sorting for progenitor 
cells. Seven patients with MDS associated with trisomy 8 were studied. FISH 
showed +8 in granulocytes, monocytes, and erythroblasts, but not in lymphocytes. 
Sorted cells of T (CD3(+)), B (CD19(+)), and NK cells (CD3(-)CD56(+)) from 
peripheral blood did not contain +8, nor did CD34(+) subpopulations from BM 
including B (CD34(+)CD19(+)), T/NK (CD34(+)CD7(+)) progenitors, and pluripotent 
stem cells (CD34(+)Thy1(+)). The +8 chromosome abnormality was identified in 
stem cells only at the level of colony-forming unit of 
granulocyte-erythrocyte-macrophage-megakaryocyte (CFU-GEMM; CD34(+)CD33(+)). It 
may thus be concluded that cells affected by trisomy 8 in the context of MDS are 
at the CFU-GEMM level and that cells of lymphoid lineage are not involved. These 
results provide new insights into the biology of MDS and suggest that intensive 
chemotherapy and autologous BM transplantation may become important therapeutic 
strategies.