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Titolo:
Regulation of the acute myeloid leukemia cell line OCI/AML-2 by endothelial nitric oxide synthase under the control of a vascular endothelial growth factor signaling system
Autore:
Koistinen, P; Siitonen, T; Mantymaa, P; Saily, M; Kinnula, V; Savolainen, ER; Soini, Y;
Indirizzi:
Oulu Univ Hosp, Dept Internal Med, Oulu, Finland Oulu Univ Hosp Oulu Finland Univ Hosp, Dept Internal Med, Oulu, Finland Oulu Univ Hosp, Dept Clin Chem, Oulu, Finland Oulu Univ Hosp Oulu Finland lu Univ Hosp, Dept Clin Chem, Oulu, Finland Oulu Univ Hosp, Dept Pathol, Oulu, Finland Oulu Univ Hosp Oulu FinlandOulu Univ Hosp, Dept Pathol, Oulu, Finland
Titolo Testata:
LEUKEMIA
fascicolo: 9, volume: 15, anno: 2001,
pagine: 1433 - 1441
SICI:
0887-6924(200109)15:9<1433:ROTAML>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
IN-VITRO; INCREASED ANGIOGENESIS; HEMATOPOIETIC-CELLS; FACTOR VEGF; STEM-CELLS; EXPRESSION; APOPTOSIS; AKT; ACTIVATION; RECEPTOR;
Keywords:
AML; VEGF; Flk-1/KDR; Pl3-k; Akt kinase; eNOS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
57
Recensione:
Indirizzi per estratti:
Indirizzo: Koistinen, P Univ Oulu, Dept Internal Med, Kajaanintie 50, FIN-90220 Oulu,Finland Univ Oulu Kajaanintie 50 Oulu Finland FIN-90220 ulu, Finland
Citazione:
P. Koistinen et al., "Regulation of the acute myeloid leukemia cell line OCI/AML-2 by endothelial nitric oxide synthase under the control of a vascular endothelial growth factor signaling system", LEUKEMIA, 15(9), 2001, pp. 1433-1441

Abstract

It is generally accepted that the vascular endothelial growth factor (VEGF) signal system has no role in the maintenance of normal blood cell formation, although it obviously regulates the development of primitive hematopoiesis during an early stage of embryogenesis. The VEGF signaling pathway, however, might have some role in malignant hematopoiesis, since malignant hematopoietic cells, including acute myeloid leukemia (AML) cells, have been shown to express VEGF and its receptors. In endothelial cells, the VEGF/Flk-1/KDR signal system is a very important generator of nitric oxide (NO) through the activation of its downstream effectors phosphatidylinositol-3-OH-kinase (P13-K), Akt kinase and endothelial NO synthase (eNOS). It is known that NO regulates hematopoiesis and modulates AML cell growth. The role of theVEGF signaling pathway in the control of AML cell growth through eNOS, however, has not been studied. By using the OCI/AML-2 cell line, which expresses VEGF receptor-2, ie Flk-1/KDR, eNOS and VEGF, as analyzed by flow cytometry, and produces VEGF into growth medium, as analyzed by ELISA, we showed that the Akt kinase and NOS activities in these cells were decreased by theinhibitors of VEGF, Flk-1/KDR and P13-K, and NOS activity also by the direct inhibitor of NOS. The decreased NOS activity led to inhibition of clonogenic cell growth and, to some extent, induction of apoptosis. We also foundthat blast cells of bone marrow samples randomly taken from 14 AML patients uniformly expressed FIk-1/KDR and to varying degrees eNOS and VEGF, as analyzed by immunohistochemistry. We conclude that autocrine VEGF through FIk-1/KDR, by activating eNOS to produce NO through P13-K/Akt kinase, maintains clonogenic cell growth in the OCI/AML-2 cell line. Since the patient sampes did not express VEGF in all cases, it is possible that in vivo the regulatory connection between these two signal systems is also mediated via endocrine VEGF in addition to autocrine or paracrine VEGF.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 03/04/20 alle ore 13:42:57