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.

Small RNA Profiling in an HTLV-1-Infected Patient with Acute Adult T-Cell Leukemia-Lymphoma at Diagnosis and after Maintenance Therapy: A Case Study

“…Their interactions and functions within the pathway are essential for proper cellular responses to TGF-β signaling [ 37 , 38 , 39 ]. Several studies have shown that abnormal expression of miRNAs can affect TGF-β signaling [ 40 ], which plays a critical role in ATLL development and progression [ 41 , 42 ]. For example, miR-26b was shown to downregulate the expression of SMAD-4, a negative regulator of TGF-β signaling, thereby promoting TGF-β signaling in affected cells [ 43 ] including leukemic cells [ 44 ].…”

Parasitism and Molecular Implication of HTLV-1 Pathogenesis

“…Decontrolled immune response for the most part by means of tolerogenic state enlistment has been recorded as an additional factor (Kannagi et al, 2012). A tolerogenic state is accomplished through the direct impact of Interleukin-10 (Mori et al, 1996) and Transforming growth factor-beta (TGFβ) (Niitsu et al, 1988) generated by infected cells. It is also achieved through the indirect activity of C-C theme chemokine ligand 22 (CCL22) produced by cells having an infection of HTLV-1 (Toulza et al, 2010).…”