Extracellular NM23 Protein as a Therapeutic Target for Hematologic Malignancies.pdfVIP

Hindawi Publishing Corporation Advances in Hematology Volume 2012, Article ID 879368, 10 pages doi:10.1155/2012/879368 Review Article Extracellular NM23 Protein as a Therapeutic Target for Hematologic Malignancies Junko Okabe-Kado, Takashi Kasukabe, and Yasuhiko Kaneko Research Institute for Clinical Oncology, Saitama Cancer Center, Komuro 818, Ina-machi, Saitama 362-0806, Japan Correspondence should be addressed to Junko Okabe-Kado, jkado@cancer-c.pref.saitama.jp Received 25 May 2011; Accepted 29 June 2011 Academic Editor: Kevin D. Bunting Copyright © 2012 Junko Okabe-Kado et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. An elevated serum level of NM23-H1 protein is a poor prognostic factor in patients with various hematologic malignancies. The extracellular NM23-H1 protein promotes the in vitro growth and survival of acute myelogenous leukemia (AML) cells and inversely inhibits the in vitro survival of normal peripheral blood monocytes in primary culture at concentrations equivalent to the levels found in the serum of AML patients. The growth and survival promoting activity to AML cells is associated with cytokine production and activation of mitogen-activated protein kinases (MAPKs) and signal transducers and activators of transcription (STAT) signaling pathways. Inhibitors specific for MAPK signaling pathways inhibit the growth/survival-promoting activity of NM23-H1. These findings indicate a novel biological action of extracellular NM23-H1 and its association with poor prognosis. These results suggest an important role of extracellular NM23-H1 in the malignant progression of leukemia