Inhibition of bone marrow stem cell growth in vitro by methylmalonic acid: a mechanism for pancytopenia in a patient with methylmalonic acidemia.
A 7-week-old infant with methylmalonic acidemia had pancytopenia and hypoplastic bone marrow. The patient responded to large doses of vitamin B12 treatment, and within 3 wk, the blood counts and bone marrow cellularity returned to normal. To understand the mechanism of marrow depression in this infant, we examined the effect of the patient's plasma and methylmalonic acid itself on the in vitro growth of bone marrow-committed stem cells. The patient's plasma obtained before B12 treatment completely inhibited the marrow cell growth, whereas the posttreatment plasma showed no inhibition. Methylmalonic acid when added to the culture dishes in concentrations comparable to those reported in plasma of methylmalonic acidemia patients, inhibited growth of marrow stem cells in a concentration-dependent fashion. On the other hand, 16 to 18 hr incubation of cells in the same concentration of methylmalonic acid did not affect the recovery of viability of the cells. The observations suggest that methylmalonic acid is inhibitory to the proliferation of marrow stem cells. The mechanism of inhibition is yet to be elucidated.
D001853:Bone Marrow / Q000187:drug effects*; D001854:Bone Marrow Cells; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D007223:Infant; D008314:Malonates / Q000097:blood*; D008661:Metabolism, Inborn Errors / Q000097:blood* / Q000209:etiology; D008764:Methylmalonic Acid / Q000097:blood* / Q000494:pharmacology; D010198:Pancytopenia / Q000209:etiology*
D008314:Malonates; D008764:Methylmalonic Acid