Bone marrow stroma from refractory anemia of myelodysplastic syndrome is defective in its ability to support normal CD34-positive cell proliferation and differentiation in vitro

We examined the supportive function of stromal cells from patients with ref ractory anemia (RA) of myelodysplastic syndrome (MDS) on CD34-positive hema topoietic cell proliferation and differentiation using a long-term bone mar row culture (LTMC) system. Primary marrow stromal cells were obtained from 11 MDS RA patients and 12 healthy volunteers, and freshly prepared CD34-pos itive bone marrow cells from a normal subject were inoculated onto the stro ma. There seems to be three broad patterns of hematopoietic cell growth in the LTMCs. In one group, hematopoietic cells were maintained at near normal levels (type A). In the second group, the number of hematopoietic cells in creased within the first 5-10 days of culture, but declined to low levels a t 15-20 days of culture as compared with normal control (type B). In the th ird group, the incidence of hematopoietic cells steadily declined from the beginning of the culture (type C). Furthermore, apoptotic change of hematop oietic cells was very frequently observed in cultures with the type C strom a, which were especially defective for supporting CD34+ cell proliferation and differentiation. The expression of CD95 on hematopoietic cells was indu ced by the type C stroma, however, production of fas ligand by the stromal cells was not observed. These findings suggest a lack of hematopoietic supp ortive function in some cases of MDS RA and also indicate that there is het erogeneity of stromal function among MDS RA patients. (C) 1999 Elsevier Sci ence Ltd. All rights reserved.