Increased Expression of the Nitric Oxide Synthase (iNOS) in the Bone Marrow of Myelodysplasia (MDS) Patients.

MDS constitutes a set of heterogeneous hematopoietic stem cell diseases that are manifested by cytopenias in spite of a cellular bone marrow. MDS carries an increased risk of acute myeloid leukemia (AML). Data suggest that overproduction of inflammatory cytokines in the marrow plays a role in the cytopenias of MDS. Nitric oxide (NO) has important functions in the immune system. Inflammatory cytokines trigger the expression of the inducible nitric oxide synthase (iNOS) and NO production. NO inhibits bone marrow progenitor cell growth and induces DNA mutations. Consequently, NO could play a role in the pathophysiology of MDS. We have evaluated iNOS expression in the bone marrow of MDS patients. Archival bone marrow biopsy samples from 10 MDS patients were compared to 10 normal bone marrow biopsies. The distribution by cases according to the FAB classification was 4 RA, 2 RARS, 3 RAEB, and 1 RAEB-T (Table). Immunohistochemical studies for human iNOS expression were performed using a polyclonal rabbit antibody. A sample was considered positive for iNOS expression when 10% or more cells were positive. Using this criterion, 7/10 MDS samples expressed iNOS while none of the normal bone marrows did (Table). iNOS expression was found exclusively in the myeloid lineage cells. Overexpression of iNOS in the bone marrow of MDS patients could lead to local overproduction of NO and therefore contribute to the ineffective hematopoiesis and cytopenias seen in early MDS. Chronic exposure to high levels of NO could enhance the risk of evolution to AML. iNOS could therefore constitute a new therapeutic target for MDS.