IN-VITRO RESPONSE OF NORMAL AND APLASTIC-ANEMIA BONE-MARROW TO MAST-CELL GROWTH-FACTOR AND IN COMBINATION WITH GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR AND INTERLEUKIN-3

We have examined the effect of mast cell growth factor (MGF), granuloc yte-macrophage colony-stimulating factor (GM-CSF), and interleukin-3 ( IL-3), singly or in combination, on the growth of normal and aplastic anemia (AA) bone marrow in clonogenic assay and long-term bone marrow culture (LTBMC). MGF stimulated colony-forming unit-granulo-cyte/macro phage (CFU-GM), burst-forming unit-erythroid (BFU-E), and mixed colony -forming unit (consisting of granulocyte-macrophage and erythroid elem ents) (CFU-GEM) colony formation from both normal and AA marrow. The t hree-factor combination stimulated the greatest number of colonies. Ma rrow from less severely affected AA patients was stimulated to produce the highest number of colonies, and a normal response was possible if progenitors were present. When added to LTBMC, MGF alone had little e ffect. GM-CSF and IL-3 stimulated increased numbers of progenitor cell s harvested each week from normal and AA LTBMC. This resulted in norma l colony numbers in some patients, the majority of whom were less seve rely affected than the patients who did not respond in LTBMC. The thre e-factor combination was additive for normal CFU-GM production. Howeve r, no further increases in AA LTBMC resulted from the addition of MGF to GM-CSF and IL-3. The partial correction in clonogenic assay with MG F in some AA patients raises the possibility of therapeutic benefit. W e failed to demonstrate increased progenitor cell numbers in AA LTBMC, however. Further studies may overcome possible limitations to progeni tor cell proliferation.