Etude du rôle de Monoxyde d’azote (NO) dans la progression du myélome Multiple (MM) et son implication dans le développement des maladies osseuses associées au MM.

Abstract

Nitric oxide (NO) is sensitive marker of inflammation and it is widely associated with cancer development. Multiple myeloma (MM) is a hematological cancer of fully differentiated plasma cells in the bone marrow which is a favorable microenvironment for the promotion of communication between malignant plasma cells MPC (Myeloma plasma cells) and other cell types using pro-inflammatory mediators. Myeloma bone diseases (MBD) and monoclonal mmunoglobulin secretion are the most visible aspects in MM.The present work aims to study the role of (NO) as an inflammatory mediator in the progression of MM and its effect on the development of MBD. We evaluated in vivo, the NO concentration in the plasma of MM patients in the Algerian East, and its possible correlation with some prognostic marker evolution, the statue of the immune system, and some bone remodeling markers in these patients. We have also carried out a study in vitro to evaluate NO production by myeloma microenvironment using MPC (RPMI 8226 cell lines) co-culture withe osteoblast ( MG63 cell line) and to investigate anti-proliferative and cytotoxic effect of iNOS inhibitor on the two cell lines co-culture . The results showed a significant increase of NO concentration in the plasma of MM patients comparing with the plasma of positive and negative controls (p> 0.01). Hence, the profile of NO concentration allowed the revealing of a slight relation with some prognostic and bone remolding markers. Furthermore we found a significant relationship between NO concentration and monocytes (p> 0.01) as well as granulocytes rate (p> 0.01) in the MM patients. In addition, the studies realized in vitro confirmed an important production of NO by myeloma cell line (RPMI 8226), which was also noticed in the case of the co-culture of myeloma cell line (RPMI 8226 ) with the osteoblast (MG63). This work has elucidated the role of NO in MM cancer and its effect on some manifestations of the disease, including MBD.