Methionine requirement of normal and leukaemic haemopoietic cells in short term cultures

The in vitro l -methionine requirement of bone marrow cells from patients with leukaemia was compared with that from patients with non-malignant diseases by means of incorporation of (methyl 3 H) thymidine into acid-insoluble material. After 24 h in a medium in which l -methionine was substituted by l -homocysteine there was a lower incorporation of (methyl 3 H) thymidine by leukaemic marrow at either 0.1 mM (normal 84 ± 15; leukaemic 60 ± 11%, p l -homocysteine (normal 76 ± 13; leukaemic 58 ± 9%, p > 0.01). The response of bone marrow cells from leukaemic patients in regression was similar to that of normal marrow. Bone marrow cells from non-leukaemic patients required a lower concentration of l -methionine in the culture media for optimal incorporation of (methyl 3 H) thymidine than did those from leukaemic patients. Bone marrow cells from leukaemic patients had a decreased maximal initial rate of l -methionine transport ( V max ) when compared with marrow cells from normal subjects, though in all cases the Km value for l -methionine transport was lower in leukaemic cells. Saturation studies suggested that the size of the cytoplasmic pool for l -methionine was larger (about two times) in marrow cells from normal subjects. These results suggest a therapeutic strategy based on a reduction of the plasma l -methionine concentration.