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Increased inducible nitric oxide synthase expression and nitric oxide concentration in patients with aplastic anemia

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Abstract

Nitric oxide (NO) is a biological mediator that is synthesized from L-arginine by the nitric oxide synthase (NOS) family. We investigated the expression of iNOS in bone marrow (BM) mononuclear cells (MNCs) using a reverse transcriptase polymerase chain reaction (RT-PCR) assay and the concentration of NO from BM serum by measuring the metabolite NO2 in 13 patients with aplastic anemia (AA) compared with 10 normal controls who were donors for allogeneic bone marrow transplantation (BMT). All samples of BM MNCs in patients with AA expressed iNOS mRNA, but iNOS was not expressed in patients who were treated successfully with allogeneic BMT. Normal control samples and samples from leukemia patients who had bone marrow aplasia after chemotherapy did not show significant iNOS expression. When we measured the density of bands for both iNOS and β2-microglobin expressed as the iNOS/β2-microglobin density ratio, there was a significant difference in the ratio between AA and normal controls (0.88±0.15 vs 0.26±0.05, P<0.001). The BM serum NO2 concentration in the patients with AA was significantly higher than that of normal controls (88.1±32.8 μM vs 48.8±8.6 μM, P=0.002). In addition, there was a significant correlation between the NO2 concentration and the calculated iNOS/β2-microglobin density ratio (r=0.567, P=0.01). These findings suggest that upregulation of iNOS expression for local NO production may contribute in part to the pathogenesis of AA.

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Acknowledgements

This study was supported by a grant of the Korea Health 21 R&D Project, Ministry of Health and Welfare, Republic of Korea (01-PJ10-PG6–01GN16–0005).

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Correspondence to H.-J. Kim.

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Chung, IJ., Lee, JJ., Nam, CE. et al. Increased inducible nitric oxide synthase expression and nitric oxide concentration in patients with aplastic anemia. Ann Hematol 82, 104–108 (2003). https://doi.org/10.1007/s00277-002-0602-0

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