Expression of TGF-beta gene in adult T cell leukemia

Abstract

Peripheral mononuclear cells from adult T cell leukemia (ATL) patients were analyzed in comparison with other types of leukemia cells, for the expression of transforming growth factor-beta (TGF-beta) mRNA, for the presence of TGF-beta activity (colony stimulating activity for normal rat kidney fibroblasts [NRK]) in conditioned medium and for their susceptibility to exogenous TGF-beta. Highly elevated TGF-beta mRNA levels were observed in all five ATL cell samples tested; however, in three acute myelogenous leukemia (AML) samples, in one acute lymphatic leukemia (ALL), and one chronic myelogenous leukemia (CML), TGF-beta expression was relatively lower. In normal peripheral mononuclear cells TGF-beta mRNA was weakly detectable. Colony stimulating activity for NRK found in the conditioned medium from ATL cells as well as other leukemia cells correlated well with the levels of TGF-beta mRNA expression. In all three ATL samples tested, stimulation of 3H- thymidine uptake by purified TGF-beta from platelets was apparent. These results suggest that ATL cells are secreting active TGF-beta in a relatively high amount, as compared with other leukemia cells, and may proliferate in response to the factor via an autocrine manner. Furthermore, considering that TGF-beta stimulates bone resorption, we can speculate that the relatively high amount of TGF-beta in ATL cells contributes to the hypercalcemia frequently seen in ATL patients.