Abstract
The nm23 gene is overexpressed in many hematological malignancies and other neoplasms. Some tumor cell lines that overexpress NM23 secrete this protein into extracellular environment. In this study, we found that the serum concentration of NM23-H1 protein was significantly higher in patients with various hematological malignancies. The serum level of NM23-H1 protein was clinically useful as a prognostic factor in malignant lymphoma and acute myelogeneous leukemia (AML). The level of NM23-H1 protein in all of the normal serum samples examined was lower than 10 ng/mL, while those in the tumors varied from about 0 to 1000 ng/mL. Exogenously added NM23-H1 protein did not affect the growth or survival of various leukemia and lymphoma cell lines. However, NM23-H1 protein inhibited the survival of adherent normal peripheral blood mononuclear cells (PBMNC) at 100–1000 ng/mL, and slightly stimulated the survival of nonadherent PBMNC. These results suggest that the effect of NM23-H1 protein on normal PBMNC may be associated with a poor prognosis in hematological malignancies.
Similar content being viewed by others
References
Anzinger, J., Malmquist, N. A., Gould, J., and Buxton, I. L. O. (2001). Proc. West. Pharmacol. Soc. 44, 61-63.
Huwer, H., Kalweit, G., Engel, M., Welter, C., Dooley, S., and Gams, E. (1997). Eur. J. Cardiothorac. Surg. 11, 206-209.
Ito, Y., Okabe-Kado, J., Honma, Y., Iwase, O., Shimamoto, T., Ohyashiki, J. H., and Ohyashiki, K. (2001). Leukemia 16, 165-169.
Lacombe, M.-L., Milon, L., Munier, A., Mehus, J. G., and Lambeth, D. O. (2000). J. Bioenerg. Biomembr. 32, 247-258.
Lacombe, M.-L., Sastre-Garau, X., Lascu, I., Vonica, A., Wallet, V., Thiery, J. P., and Veron, M. (1991). Eur. J. Cancer 27, 1302-1307.
Leone, A., Seeger, R. C., Hong, C. M., Hu, Y. Y., Arboleda, M. J., Brodeur, G. M., Stram, D., Slamon, D. J., and Steeg, P. S. (1993). Oncogene 8, 855-865.
Malmquist, N. A., Anzinger, J. J., Hirzel, D., and Byxton, I. O. L. (2001). Proc. West. Pharmacol. Soc. 44, 57-59.
Niitsu, N., Honma, Y., Iijima, K., Takagi, T., Higashihara, M., Sawada, U., and Okabe-Kado, J. (2003). Leukemia. 17, 196-202.
Niitsu, N., Okabe-Kado, J., Kasukabe, T., Yamamoto-Yamaguchi, Y., Umeda, M., and Honma, Y. (1999). Blood 94, 3541-3550.
Niitsu, N., Okabe-Kado, J., Nakayama, M., Wakimoto, N., Sakashita, A., Maseki, N., Motoyoshi, K., Umeda, M., and Honma, Y. (2000). Blood 96, 1080-1086.
Niitsu, N., Okabe-Kado, J., Okamoto, M., Takagi, T., Yoshida, T., Aoki, S., Hirano, M., and Honma, Y. (2001a). Blood 97, 1202-1210.
Niitsu, N., Okamoto, M., Okabe-Kado, J., Takagi, T., Yoshida, T., Aoki, S., Honma, Y., and Hirano, M. (2001b). Leukemia 15, 832-839.
Okabe-Kado, J. (2002). Leuk. Lymphoma 43, 859-867.
Okabe-Kado, J., Hayashi, M., Honma, Y. and Hozumi, M. (1985, 1988). Cancer Res. 45, 4848-4852.
Okabe-Kado, J., Kasukabe, T., Honma, Y., Hayashi, M., Henzel, W. J. and Hozumi, M. (1992). Biochem. Biophys. Res. Commun. 182, 987-994.
Okabe-Kado, J., Kasukabe, T., Honma, Y., and Hozumi, M. (1988). J. Biol. Chem. 263, 10994-10999.
Urano, T., Furukawa, K., and Shiku, H. (1994). Oncogene 8, 1371-1376.
Wakimoto, N., Yokoyama, A., Okabe-Kado, J., Nagata, K., Motoyoshi, K., and Honma, Y. (1998). Br. J. Cancer 77, 2298-2303.
Willems, R., Van Bockstaele, D. R., Landon, F., Lenjou, M., Nijs, G., Snoeck, H.-W., Berneman, Z. N., and Slegers, H. (1998). J. Biol. Chem. 273, 13663-13668.
Yokoyama, A., Okabe-Kado, J., Wakimoto, N., Kobayashi, H., Sakashita, A., Maseki, N., Nakamaki, T., Hino, K., Tomoyasu, S., Tsuruoka, N., Motoyoshi, K., Nagata, N., and Honma, Y. (1998). Blood 91, 1845-1851.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Okabe-Kado, J., Kasukabe, T. Physiological and Pathological Relevance of Extracellular NM23/NDP Kinases. J Bioenerg Biomembr 35, 89–93 (2003). https://doi.org/10.1023/A:1023402125186
Issue Date:
DOI: https://doi.org/10.1023/A:1023402125186