Alpha V Beta 3 Integrin Expression And Mitogenic Effects By Thyroid Hormones In Chronic Lymphocytic Leukemia

Background: Chronic lymphocytic leukemia (CLL) is the most common adult leukemia. The thyroid hormones, T3 and T4, bind the alpha v beta 3 integrin and activate phosphorylates ERK (pERK). These tumor-promoting actions were reported in a number of malignancies, but not in CLL. Methods: Primary cells from 22 CLL patients were verified for disease markers (CD5/CD19/CD23) and analyzed for alpha v beta 3 by flow cytometry (FC), ImageStream, Western blots (WB), and immunohistochemistry (IHC) in archival bone marrow (BM, n = 6) and lymph node (LN, n = 5) tissues. Selected samples (n = 8) were incubated with T3 (1-100 nM) or T4 (0.1-10 mu M) for 30 min, and the expression levels of alpha v beta 3, pERK and PCNA (cell proliferation marker) were determined (WB). Results: alpha v beta 3 was detected on the membrane of circulating CLL cells and in the BM but not in the LN. T3 and T4 enhanced alpha v beta 3 protein levels in primary CLL cells. Similarly, pERK and PCNA were rapidly induced in response to T3 and T4 exposure. Conclusions: alpha v beta 3 integrin is expressed on primary CLL cells and is induced by thyroid hormones. We further suggest that the hormones are mitogenic in these cells, presumably via alpha v beta 3-mediated signaling.