Differential effect of transforming growth factor beta 1 on the proliferation of human lymphoid and myeloid leukemia cells

BACKGROUND. Transforming Growth Factor beta (TGF beta) exerts different effects on the hemopoietic system which range from the growth stimulation of more mature myeloid progenitors to the growth inhibition of more immature and multilineage hemopoietic precursors. TGF beta is also an inhibitor of the proliferation and functional activities of normal T and B lymphocytes. The aim of this study was to evaluate its effect on the growth of a human leukemic cells of lymphoid and myeloid origin. METHODS. We tested its activity on the doubling time, the DNA synthesis rate and the clonal growth of a panel of lymphoid and myeloid leukemic cell lines. RESULTS. Among the myeloid cell lines, the proliferation in liquid cultures as well as the clonal growth of KG1, HL60 and U937 were suppressed by TGF beta 1 at doses ranging from 0.025 to 2.5 ng/ml; the degree of inhibition was, however, variable. BV 137, a Ph1-positive cell line derived from a very undifferentiated stem cell, was also highly responsive to TGF beta 1 inhibition. Among the six lymphoid neoplastic cell lines, only Nalm 6, a pre-B leukemic cell line, was consistently and reproducibly inhibited by the same doses of TGF beta 1. Conversely, two Burkitt lymphoma cell lines, Raji and Daudi, and three T-cell leukemias (Molt 4, Jurkat and PF 382) were insensitive to TGF beta inhibition.