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

Niitsu, Nozomi; Honma, Yoshio; Iijima, Kimiko; Takagi, Toshiyuki; Higashihara, Masaaki; Sawada, Umihiko; Okabe‐Kado, Junko

doi:10.1038/sj.leu.2402699

Cited by 23 publications

(23 citation statements)

References 26 publications

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“…3 We previously reported that the nm23-H1 protein was strongly expressed on the surface of neoplastic cells of PTCL and extranodal NK/T-cell lymphomas, 4 and we also observed a significant correlation between the serum nm23-H1 level and the degree of its cell surface expression. This suggested that the serum nm23-H1 level reflects the proliferation rate of lymphoma cells, and that, in PTCL and NK-NHL, large amounts of nm23-H1 molecules are secreted from the neoplastic cells.…”

Section: Figuresupporting

confidence: 59%

Serum levels of the nm23-H1 protein and their clinical implication in extranodal NK/T-cell lymphoma

et al. 2003

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Section: Figuresupporting

confidence: 59%

Serum levels of the nm23-H1 protein and their clinical implication in extranodal NK/T-cell lymphoma

et al. 2003

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“…Cell surface Nm23-H1 has been previously observed on NHL cells (18) and some myeloid cell lines (10,19). However, to our knowledge, this is the first time that binding of Nm23-H1 to AML cells from an exogenous soluble pool of protein, commensurate with that found in AML patients, has been shown.…”

Section: Discussionmentioning

confidence: 73%

“…In one study in non-Hodgkin's lymphoma (NHL), more than 20% of cells were positive for Nm23-H1 cell surface expression in more than 25% of cases (18). The authors went on to show that NHL patients with high Nm23-H1 cell surface expression had significantly reduced survival rates.…”

Section: Introductionmentioning

confidence: 99%

Nm23-H1 Indirectly Promotes the Survival of Acute Myeloid Leukemia Blast Cells by Binding to More Mature Components of the Leukemic Clone

et al. 2011

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Nm23-H1 plays complex roles in the development of diverse cancers including breast carcinoma, high-grade lymphomas, and acute myeloid leukemia (AML). In the case of AML and lymphomas, serum Nm23-H1 protein is elevated with the highest levels correlating with poorest prognosis. A recent study identified that this association is most likely causal in AML and that Nm23-H1 acts as an AML cell survival factor. In this study, we report heterogeneity in the ability of AML samples to bind and respond to Nm23-H1, and we offer evidence that binding is essential for improved survival. Further, we show that the subset of AMLs that bind Nm23-H1 do not do so through the putative Nm23-H1 receptor MUC1*. Although rNm23-H1 promoted the survival of the most primitive blasts within responding AMLs, it was not these cells that actually bound the protein. Instead, rNm23-H1 bound to more mature CD34 lo /CD34 À and CD11b þ cells, revealing an indirect survival benefit of Nm23-H1 on primitive blasts. In support of this finding, the survival of purified blast cells was enhanced by medium conditioned by more mature cells from the clone that had been stimulated by rNm23-H1. Levels of interleukin 1b (IL1b) and IL6 in rNm23-H1 conditioned medium mirrored the potency of the conditioned media to promote blast cell survival. Furthermore, Nm23-H1 expression was significantly associated with IL1b and IL6 expression in primary uncultured AML samples. These findings have implications for the role of Nm23-H1 in AML and its use as a prognostic marker. Additionally, they offer the first evidence of novel cross-talk between cell populations within the tumor clone. Cancer Res; 71(3); 1177-86. Ó2010 AACR.

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“…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. In the present study, we, therefore, evaluated intracellular nm23-H1 protein expression using immunohistochemistry.…”

Section: Introductionmentioning

confidence: 99%

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

Niitsu

Nakamine²,

Okamoto³

et al. 2004

Clinical Cancer Research

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Purpose: Recently, we established an ELISA technique for measuring nm23-H1 protein in serum and found that the serum nm23-H1 level is a potential prognostic factor for patients with non-Hodgkin's lymphoma.Experimental Design: We used immunohistochemistry to examine the expression of nm23-H1 by the lymphoma cells in patients with diffuse large B-cell lymphoma (DL-BCL).Results: By analyzing a consecutive series of 172 untreated DLBCL patients, we found that 100 (58.1%) were strongly positive. The cytoplasmic nm23 expression in lymphoma cells correlated significantly with the serum nm23-H1 level. There was a significant correlation between patients with cytoplasmic nm23-positive lymphoma and those with performance status 2-4, stage III/IV, bulky mass, B symptoms, elevated serum level of soluble interleukin 2 receptor, and elevated serum level of C-reactive protein.Overall and progression-free survival rates were significantly lower in patients with nm23-H1-positive lymphomas than in those with nm23-H1-negative lymphomas. Similar difference was seen between patients with high and low serum levels of nm23-H1. Thus, the correlation between presence or absence of cytoplasmic nm23-H1 expression and serum nm23-H1 levels suggests that serum nm23-H1 is produced directly by lymphoma cells. Conclusion:We suggest that nm23-H1 expression is a prognostic factor for DLBCL, and that it is as important as serum nm23-H1, both of which are useful for planning a treatment strategy.

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

Cited by 23 publications

References 26 publications

Serum levels of the nm23-H1 protein and their clinical implication in extranodal NK/T-cell lymphoma

Serum levels of the nm23-H1 protein and their clinical implication in extranodal NK/T-cell lymphoma

Nm23-H1 Indirectly Promotes the Survival of Acute Myeloid Leukemia Blast Cells by Binding to More Mature Components of the Leukemic Clone

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

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