Expression and phosphorylation status of retinoblastoma protein in adult T-cell leukemia/lymphoma

The deletion or hyperphosphorylation of the retinoblastoma protein (pRB), i s reported to progress various tumors. But its relevance to adult T-cell le ukemia/lymphoma (ATL) remains to be elucidated. To better understand the ro le of pRB in ATL, we examined the expression and phosphorylation status of pRB in three ATL cell lines and 43 clinical samples, eight peripheral blood samples and 35 lymph node samples, from patients with ATL by Western blott ing. In addition, 30 lymph node sections were also evaluated immunohistoche mically. As a result, Western blotting analysis revealed that the pRB in th e ATL cell lines was in the hyperphosphorylated, but that in 39 of 43 clini cal samples, pRB was exclusively in the hypophosphorylated form. Four perip heral blood samples were negative for pRB. Immunohistochemistry revealed th at the lymph nodes of all of 30 patients tested were positive for pRB at va rious staining levels, weak, mild, and strong. But weak expression may be e ssentially negative for pRB function. Patients with weak pRB expression in their lymph nodes lived significantly shorter lives than those with mild ex pression. Surprisingly, patients with strong expression also showed a signi ficantly worse prognosis than those with mild expression. Although only the absence of pRB expression was considered previously to be indicative of RE functional loss, it has been reported recently that overexpression of pRB is correlated with progression of disease in patients with advanced bladder carcinoma or follicular lymphoma. These findings indicate that pRB control s tumor proliferation not only as a cell cycle regulator but also by other mechanisms, possibly through the inhibition of apoptosis, as suggested by r ecent findings in an osteosarcoma cell line, Saos-2. In conclusion, pRB may play an essential role in its hypophosphorylated form for progression of A TL, as well as a cell cycle promoter in hyperphosphorylated or negative/exc essive reduced form. (C) 2000 Elsevier Science Ltd. All rights reserved.