Thiorphan stimulates clonal growth of GM-CFU in short term cultures of bone marrow from a healthy donor and from patients with non-Hodgkin lymphoma

Thiorphan, a specific inhibitor of membrane neutral endopeptidase (NEP, EC 3.4.24.11) also known as the common acute lymphoblastic leukemia antigen (C ALLA, CD10) was added into short-term clonal cultures of the buffy coat con centrates of human bone marrow obtained from a healthy donor (six experimen ts) and from ten patients with non-Hodgkin lymphoma (NHL) (eight in complet e remission, one in partial remission and one in relapse). Thiorphan concen trations ranged from 10(-5) to 10(-13) M. Nanomolar and higher concentratio ns of the drug mildly stimulated the granulocyte-macrophage colony-forming unit (GM-CFU counts in the cultures of normal bone marrow, reaching the sig nificance at 10(-7) M. Meaningful alterations of the GM-CFU counts were not ed in 31 of 79 thiorphan-treated cultures of NHL bone marrow (39%). In thos e cultures the stimulatory effects (33%) outnumbered the inhibitory ones (6 %). The stimulatory effects occurred mainly in the bone marrow samples of t he patients with highly malignant NHL. The observations are compatible with the idea that the membrane endopeptidase (CALLA, CD10) participates in pro cesses controlling the proliferation and differentiation of hematopoetic ce lls by cleaving the neuropeptides and related hemoregulatory peptides. (C) 1998 Elsevier, Paris.