Shedding by ADAM10 and ADAM17 is associated with progression of adult T-cell leukemia/lymphoma

Abstract

Adult T-cell leukemia/lymphoma (ATL) is a retrovirus-associated mature T-cell leukemia/lymphoma. It is speculated that ATL is an age-related disease and some changes are involved in malignant transformation and monoclonal expansion of the HTLV-1-infected cells. We previously reported that HTLV-1-infected cells and ATL cells exhibit CD30 and soluble CD30 (sCD30) is elevated in the sera of patients with ATL. Recently, we also evaluated the levels of sCD30 in ATL patients underwent chemotherapy and allogeneic hematopoietic stem cell transplantation (HSCT) to predict prognosis of ATL patients under 2 different clinical settings; before initiation therapy and before HSCT. Our results suggest that sCD30 may be a useful biomarker in HSCT therapy, because a high sCD30 level before HSCT was implicated in early death after HSCT. In addition, we report that sCD30 elevation was followed by acute crisis from chronic type of ATL. Previously, high levels of soluble proteins including cytokine receptor and membrane-binding protein were observed in patients with ATL. A disintegrin and metalloproteinase (ADAM)10 and ADAM17 worked as sheddases of CD30 as well as the other proteins. ADAM10/17 also cleaved collagen and elastin which are structural proteins of tissues and may cause the tissue injury of important organs. It seems that ADAM10/17 plays a role as oncoproteins for tumorigensis in ATL.