title: Extracellular NM23-H1 protein inhibits the survival of primary cultured normal human peripheral blood mononuclear cells and activates the cytokine production.
abstract: An elevated serum level of NM23-H1 protein is found in acute myelogenous leukemia (AML) and predicts a poor treatment outcome for AML patients. To investigate the potential pathological link between the elevated serum level of this protein and poor prognosis, we examined the extracellular effects of recombinant NM23-H1 protein on the in vitro survival of primary cultured normal peripheral blood mononuclear cells (PBMNC) at concentrations equivalent to the levels found in the serum of AML patients. Extracellular NM23-H1 protein inhibited the in vitro survival of PBMNC and promoted the production of various cytokines, such as GM-CSF and IL-1beta, which in fact promoted the growth of primary cultured AML cells. These findings indicate a novel biological action of extracellular NM23-H1 and its association with poor prognosis of patients with elevated serum levels of NM23-H1 protein. These results suggest an important role of extracellular NM23-H1 in the malignant progression of leukemia and a potential therapeutic target for these malignancies.
authors: Research Institute for Clinical Oncology, Saitama Cancer Center, Komuro 818, Ina-machi, Kita-adachi-gun, Saitama, 362-0806, Japan. jkado@cancer-c.pref.saitama.jp.
authors: Junko
authors: J
authors: Okabe-Kado
authors: Research Institute for Clinical Oncology, Saitama Cancer Center, Komuro 818, Ina-machi, Kita-adachi-gun, Saitama, 362-0806, Japan.
authors: Takashi
authors: T
authors: Kasukabe
authors: Department of Life Science, Shimane University Faculty of Medicine, Shimane, Japan.
authors: Yoshio
authors: Y
authors: Honma
authors: Hematology Clinic, Saitama Cancer Center Hospital, Saitama, Japan.
authors: Hirofumi
authors: H
authors: Kobayashi
authors: Hematology Clinic, Saitama Cancer Center Hospital, Saitama, Japan.
authors: Nobuo
authors: N
authors: Maseki
authors: Research Institute for Clinical Oncology, Saitama Cancer Center, Komuro 818, Ina-machi, Kita-adachi-gun, Saitama, 362-0806, Japan.|Hematology Clinic, Saitama Cancer Center Hospital, Saitama, Japan.
authors: Yasuhiko
authors: Y
authors: Kaneko
mesh_terms: D001323:Autoantibodies / Q000097:blood; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology*; D016207:Cytokines / Q000097:blood / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood; D006801:Humans; D066298:In Vitro Techniques; D007948:Leukemia, Monocytic, Acute / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D054778:NM23 Nucleoside Diphosphate Kinases / Q000097:blood* / Q000235:genetics / Q000494:pharmacology; D011379:Prognosis; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D001323:Autoantibodies; D016207:Cytokines; D054778:NM23 Nucleoside Diphosphate Kinases; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C517938:NME1 protein, human