Serum nm23-H1 protein as a prognostic factor for indolent non-Hodgkin's lymphoma

Abstract

Standard chemotherapy has been ineffective for improving the poor 10-year survival rate of patients with indolent lymphoma. However, a wider choice of therapeutic modalities has become recently available, including immunotherapy with monoclonal antibodies and allogeneic peripheral blood stem cell transplantation. Accordingly, a sensitive prognostic indicator is required to identify high-risk patients and to help design new therapeutic approaches for them. We previously reported that the serum nm23-H1 protein level was an independent prognostic factor for aggressive lymphoma. The present study was performed to assess the clinical implications of this protein on indolent lymphoma and whether it can be used to classify the aggressiveness of the disease in order to assist in the individualization of therapy. A total of 130 patients with indolent lymphoma were enrolled in this multicenter study. The serum nm23-H1 protein level was significantly higher in patients with indolent lymphoma than in a normal control group. In addition, indolent lymphoma patients with higher nm23-H1 levels had worse overall and progression-free survival rate than those with lower nm23-H1 levels. Therefore, nm23-H1 in serum may be useful for identifying a distinct group of patients at high risk. Leukemia (2001) 15, 832-839.

Clinical significance of nm23-H1 proteins expressed on cell surface in non-Hodgkin's lymphoma

“…The expression of cell surface nm23-H1 was high in NK/T cell lymphomas compared with B cell lymphomas and we reported similar results for serum nm23-H1. 8 A significant correlation was found between cell surface nm23-H1 and serum nm23-H1, which may suggest the possibility of cell surface nm23-H1 being liberated into serum. We also identified a significant correlation between serum nm23-H1, but not cell surface nm23-H1, and Leukemia certain other prognostic factors, namely LDH or sIL-2R.…”

“…[7][8][9] Briefly, 96-well plates (Corning, Corning, NY, USA) were coated with a monoclonal anti-nm23-H1 antibody (Seikagakukougyo, Tokyo, Japan), washed four times with PBS, and incubated with 25% Block Ace solution (Dainihon Seiyaku, Osaka, Japan). Serum samples were diluted two-fold with PBS and 50 l aliquots were added to the wells.…”

“…We previously reported that serum levels of nm23-H1 in aggressive NHL and acute myelogenous leukemia (AML) were significantly higher than those in controls, and that high nm23-H1 levels correlated with poor prognosis in both aggressive NHL and AML. [7][8][9] In a collaborative study between many institutions involving a large number of patients, we found that serum nm23-H1 was an important independent prognostic factor in NHL for diffuse large B cell lymphoma (DLBCL) and peripheral T cell lymphoma (PTCL). 8 We also examined four distinct risk groups defined by the widely used clinical international prognostic index (IPI) and demonstrated that when serum nm23-H1 protein levels are high, prognosis is poor in all four risk groups.…”

“…[7][8][9] In a collaborative study between many institutions involving a large number of patients, we found that serum nm23-H1 was an important independent prognostic factor in NHL for diffuse large B cell lymphoma (DLBCL) and peripheral T cell lymphoma (PTCL). 8 We also examined four distinct risk groups defined by the widely used clinical international prognostic index (IPI) and demonstrated that when serum nm23-H1 protein levels are high, prognosis is poor in all four risk groups. Given these results, measurement of nm23-H1 protein may be useful in the treatment method selection process.…”

Clinical Significance of Intracytoplasmic nm23-H1 Expression in Diffuse Large B-Cell Lymphoma

“…We previously reported that serum levels of nm23-H1 in aggressive nonHodgkin's lymphomas and acute myelogenous leukemia were significantly higher than those in controls, and that high nm23-H1 levels correlated with poor prognosis in both aggressive non-Hodgkin's lymphomas and acute myelogenous leukemia (5,6). In a multi-institutional study involving a large number of patients, we found that serum nm23-H1 was an important and independent prognostic factor for patients with DLBCL and with peripheral T-cell lymphoma (9). Although there were still several unknowns, including the question of whether serum nm23-H1 is produced by lymphoma cells directly, and whether there is a correlation between serum nm23-H1 and intracellular nm23-H1 expression by the tumor cells, our subsequent studies (10,11) indicated that these factors are possible.…”