DEFICIENT PROLIFERATION OF MYELOID, ERYTHROID, AND MULTIPOTENT PROGENITOR CELLS IN LONG-TERM MARROW CULTURES FROM PATIENTS WITH APLASTIC-ANEMIA TREATED WITH IMMUNOSUPPRESSIVE THERAPY

By using Dexter-type long-term marrow cultures (D-LTMC), it has been s hown previously that hematopoietic progenitor cells (HPC) from patient s with aplastic anemia (AA) have a deficient proliferation in vitro. T he studies reported to date, however, have focused exclusively on gran ulomonocytic progenitors and no information exists on erythroid or mul tipotent progenitor cells. On the other hand, in such studies, the inp ut progenitor cell numbers were significantly below normal levels, thu s suggesting that the rapid disappearance of myeloid progenitor cells from AA D-LTMC could also be due, at least in part, to their reduced n umber at culture onset. In the present study, we have followed the kin etics of myeloid, erythroid, and multipotent progenitors, from 24 AA p atients subjected to immunosuppressive therapy (including patients tha t achieved complete, partial, or no remission at all), throughout a se ven-week culture period. For analysis, we grouped all the patients bas ed on their initial content of all three types of progenitors, Thus, w e were able to evaluate separately the kinetics of these cells in D-LT MC from patients with normal and subnormal levels of progenitor cells, At the time of marrow sampling, most patients showed decreased levels of HPC; in fact, only 21%, 8%, and 16% of them showed normal levels o f myeloid, erythroid, and multipotent progenitors, respectively. When cultured in D-LTMC, HPC from all AA patients analyzed showed a relativ ely fast disappearance from the cultures. Indeed, myeloid progenitors could be detected for only six weeks, whereas erythroid and multipoten t progenitors disappeared from the cultures after two and one weeks of culture, respectively. In contrast, in normal marrow D-LTMC, myeloid, erythroid, and multipotent progenitors were detected for at least sev en, five, and three weeks, respectively. Such a deficient proliferatio n was observed even in cultures of AA patients that contained normal l evels of HPC at culture onset, Interestingly, no correlation was found between HPC proliferation in D-LTMC and response to treatment. Thus, the results of this study indicate the presence of a functional in vit ro deficiency in the hematopoietic system of patients with AA, includi ng those that achieved partial or complete remission after immunosuppr essive treatment. Furthermore, this work suggests that such a prolifer ation deficiency is more pronounced in erythroid and multipotent proge nitors than in their myeloid counterparts. Am. J. Hematol. 59:149-155 1998, (C) 1998 Wiley-Liss, Inc.