Home Cellular and plasma nitrite levels in myeloid leukemia: a pathogenetic decrease
Article
Licensed
Unlicensed Requires Authentication

Cellular and plasma nitrite levels in myeloid leukemia: a pathogenetic decrease

  • Mili Jain EMAIL logo , Ashutosh Kumar , Uma Shankar Singh , Rashmi Kushwaha , Abhishek Kumar Singh , Madhu Dikshit and Anil Kumar Tripathi
Published/Copyright: June 15, 2017

Abstract

Nitric oxide (NO) has a contributory role in hemopoietic cell growth and differentiation. The effects of NO on leukemic cell growth have been predominantly studied in in vitro settings. This study was done to assess the alterations in nitrite level in myeloid leukemias. Thirty-six newly diagnosed cases of myeloid leukemia (16 AML and 20 CML) were enrolled in the study. Neutrophil precursors from the marrow aspirate and peripheral blood were separated into cell bands using the Percoll density gradient method of Borregard and Cowland. The blood plasma and marrow fluid was also collected. Nitrite (stable non-volatile end product of NO) was estimated in the cell bands, blood plasma and marrow fluid using Griess reagent. The mean nitrite level in all cell bands from peripheral blood, bone marrow, blood plasma, and marrow fluid of cases was significantly lower as compared to corresponding value in the controls. No significant difference between AML and CML was seen. On follow-up, analysis of 13 CML patients higher nitrite levels were seen (p>0.05). The significant decrease in nitrite levels in myeloid leukemia suggests a decrease in nitric oxide synthase (NOS) activity. Further work may unfold molecular targets for therapeutic role of NO modulators.

Acknowledgement

The authors thank Dr. Ayush Shukla for valuable input during the drafting of the manuscript.

References

Aicher, A., Heeschen, C., Mildner-Rihm, C., Urbrich, C., Ihling, C., Technau-Ihling, K., Zeiher, A.M., and Dimmeler, S. (2003). Essential role of endothelial nitric oxide synthase for mobilization of stem and progenitor cells. Nat. Med. 9, 1370–1376.10.1038/nm948Search in Google Scholar

Amin, A.R., Attur, M., Vyas, P., Leszczynska-Piziak, J., Levartovsky, D., Rediske, J., Clancy, R.M., Vora, K.A., and Abramson, S.B. (1995). Expression of nitric oxide synthase in human peripheral blood mononuclear cells and neutrophils. J. Inflamm. 47, 190–205.Search in Google Scholar

Awasthi, D., Singh, A.K., Dubey, M., Nagarkoti, S., Barthwal, M.K., and Dikshit, M. (2016). iNOS over expression reduces K562 cell proliferation and promotes neutrophilic defferentiatin. J. Immunol. 202, 23.Search in Google Scholar

Bain, B.J., and Lewis, S.M. (2006). Preparation and staining methods for blood and bone marrow films. In: Dacie & Lewis Practical Hematology, S.M. Lewis, B.J. Bain and I. Bates, eds. (Philadelphia: Churchill Livingstone), pp. 59–77.10.1016/B0-44-306660-4/50008-8Search in Google Scholar

Bennett, J.M., Catovsky, D., Daniel, M.T., Flandrin, G., Galton, D.A., Gralnick, H.R., and Sultan, C. (1985). Proposed revised criteria for the classification of acute myeloid leukemia. A report of the French-American-British Cooperative Group. Ann. Intern. Med. 103, 620–625.10.7326/0003-4819-103-4-620Search in Google Scholar

Boyum, A. (1968). Isolation of mononuclear cells and granulocytes from human blood. Isolation of mononuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g. Scand. J. Clin. Lab. Invest. 97, 77–89.Search in Google Scholar

Brandão, M.M., Soares, E., Salles, T.S., and Saad, S.T. (2001). Expression of inducible nitric oxide synthase is increased in acute myeloid leukaemia. Acta Haematol. 106, 95–99.10.1159/000046596Search in Google Scholar

Cedergren, J., Follin, P., Forslund, T., Lindmark, M., Sundqvist, T., and Skogh, T. (2003). Inducible nitric oxide synthase (NOS II) is constitutive in human neutrophils. Acta Pathol. Microbiol. Immunol. Scand. 111, 963–968.10.1034/j.1600-0463.2003.1111008.xSearch in Google Scholar

Chlichlia, K., Peter, M.E., Rocha, M., Scaffidi, C., Bucur, M., Krammer, P.H., Schirrmacher, V., and Umansky, V. (1998). Caspase activation is required for nitric oxide–mediated, CD95 (APO-1/Fas)–dependent and independent apoptosis in human neoplastic lymphoid cells. Blood 91, 4311–4320.10.1182/blood.V91.11.4311Search in Google Scholar

Cowland, J.B. and Borregaard, N. (1999). Isolation of neutrophil precursors from bone marrow for biochemical and transcriptional analysis. J. Immunol. Methods 232, 191–200.10.1016/S0022-1759(99)00176-3Search in Google Scholar

Crowell, J.A., Steele, V.E., Sigman, C.C., and Fay, J.R. (2003). Is inducible nitric oxide synthase a target for chemoprevention? Mol. Cancer Ther. 2, 815–823.Search in Google Scholar

Ferry-Dumazet, H., Mamani-Matsuda, M., Dupouy, M., Belloc, F., Thiolat, D., Marit, G., Arock, M., Reiffers, J., and Mossalayi, M.D. (2002). Nitric oxide induces the apoptosis of human BCR-ABL-positive myeloid leukemia cells: evidence for the chelation of intracellular iron. Leukemia 16, 708–715.10.1038/sj.leu.2402404Search in Google Scholar PubMed

Förstermann, U., Boissel, J.P., and Kleinert, H. (1998). Expressional control of the ‘constitutive’ isoforms of nitric oxide synthase (NOS I and NOS III). FASEB J. 12, 773–790.10.1096/fasebj.12.10.773Search in Google Scholar

Fujimoto, H., Ando, Y., Yamashita, T., Terazaki, H., Tanaka, Y., Sasaki, J., Matsumoto, M., Suga, M., and Ando, M. (1997). Nitric oxide synthase activity in human lung cancer. Jpn. J. Cancer Res. 88, 1190–1198.10.1111/j.1349-7006.1997.tb00348.xSearch in Google Scholar PubMed PubMed Central

Geng, Y.J., Hellstrand, K., Wennmalm, A., and Hansson, G.K. (1996). Apoptotic death of human leukemic cells induced by vascular cells expressing nitric oxide synthase in response to gamma-interferon and tumor necrosis factor α. Cancer Res. 56, 866–874.Search in Google Scholar

Ghaffari, M.A., Kadkhodaei-Elyaderani, M., Saffari, M.R., and Pedram M. (2005). Monitoring of serum nitric oxide in patients with acute leukemia. Iran J. Pharm. Res. 4, 233–237.Search in Google Scholar

Ghalaut, V.S., Sangawan, L., Dahiya, K., Ghalaut, P.S., Dhankar, R., and Saharan, R. (2012). Effect of imatinib therapy with and without turmeric powder on nitric oxide levels in chronic myeloid leukemia. J. Oncol. Pharm. Pract. 18, 186–190.10.1177/1078155211416530Search in Google Scholar

Guistarini, D., Rossi, R., Milzani, A., and Dalle-Donne, I. (2008). Nitrite and nitrate measurement by Griess reagent in human plasma: evaluation of interferences and standardization. Methods Enzymol. 440, 361–380.10.1016/S0076-6879(07)00823-3Search in Google Scholar

Jea, J.C., Liu, T.C., Wang, S.Y., and Sung, Y.J. (1998). Nitric oxide enhances the growth of U937 human leukemic cells through a cyclooxygenase-mediated pathway. J. Leukoc. Biol. 64, 451–458.10.1002/jlb.64.4.451Search in Google Scholar

Kelm, H., Priek-Steinhoff, H., Priek, M., and Straurer, B.E. (1999). Serum nitrite sensitively reflects endothelial NO formation in human forearm vasculature: evidence for biochemical assessment of the endothelial L-arginine-NO pathway. Cardiovasc. Res. 41, 765–772.10.1016/S0008-6363(98)00259-4Search in Google Scholar

Kitagawa, M., Takahashi, M., Yamaguchi, S., Inoue, M., Ogawa, S., Hirokawa, K., and Kamiyama, R. (1999). Expression of inducible nitric oxide synthase (NOS) in bone marrow cells of myelodysplastic syndromes. Leukemia 13, 699–703.10.1038/sj.leu.2401407Search in Google Scholar PubMed

Koistinen, P., Siitonen, T., Mäntymaa, P., Säily, M., Kinnula, V., Savolainen, E.R., and Soini, Y.(2001). 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, 1433–1441.10.1038/sj.leu.2402217Search in Google Scholar PubMed

Kolb, J.P. (2000). Mechanisms involved in the pro and antiapoptotic role of NO in human leukemia. Leukemia 14, 1685–1694.10.1038/sj.leu.2401896Search in Google Scholar PubMed

Krasnov, P., Michurina, T., Packer, M.A., Stasiv, Y., Nakaya, N., Moore, K.A., Drazan, K.E., and Enikolopov, G. (2008). Neuronal nitric oxide synthase contributes to the regulation of hematopoiesis. Mol. Med. 14, 141–149.10.2119/2007-00011.KrasnovSearch in Google Scholar PubMed PubMed Central

Kucukkaya, B., Ozturk, O.G., and Yalcintepe, B. (2006). Nitric oxide levels during erythroid differentiation in K562 cell line. Ind. J. Biochem. Biophys. 43, 251–253.Search in Google Scholar

Kumar, S., Barthwal, M.K., and Dikshit, M. (2010a). CDK2 nitrosylation and loss of mitochondrial potiential mediate NO-dependent biphasic effect on HL-60 cell cycle. Free Radic. Biol. Med. 48, 851–861.10.1016/j.freeradbiomed.2010.01.004Search in Google Scholar PubMed

Kumar, S., Jyoti, A., Keshari, R.S., Singh, M., Barthwal, M.K., and Dikshit, M. (2010b). Functional and molecular characterization of NOS isoforms in rat neutrophil precursor cells. Cytometry A 77, 467–477.10.1002/cyto.a.20852Search in Google Scholar PubMed

Lee, J.W., Beckham, C., Michel, B.R., Rosen, H., and Deeg, H.J. (1997). HLA-DR – mediated signals for hematopoiesis and induction of apoptosis involve but are not limited to a nitric oxide pathway. Blood 90, 217–225.10.1182/blood.V90.1.217Search in Google Scholar

Maciejewski, J.P., Selleri, C., Sato, T., Cho, H.J., Keefer, L.K., Nathan, C.F., and Young, N.S. (1995). Nitric oxide suppression of human hematopoiesis in vitro. Contribution to inhibitory action of interferon-γ and tumor necrosis factor-α. J. Clin. Invest. 96, 1085–1092.10.1172/JCI118094Search in Google Scholar

Michurina, T., Krasnov, P., Balazs, A., Nakaya, N., Vasilieva, T., Kuzin, B., Khrushchov, N., Mulligan, R.C., and Enikolopov, G. (2004). Nitric oxide is a regulator of hematopoietic stem cell activity. Mol. Ther. 10, 241–248.10.1016/j.ymthe.2004.05.030Search in Google Scholar

Peláez, B., Campillo, J.A., López-Asenjo, J.A., and Subiza, J.L. (2001). Cyclophosphamide induces the development of early myeloid cells suppressing tumor cell growth by a nitric oxide-dependent mechanism. J. Immunol. 166, 6608–6615.10.4049/jimmunol.166.11.6608Search in Google Scholar

Punjabi, C.J., Laskin, D.L., Heck, D.E., and Laskin, J.D. (1992). Production of nitric oxide by murine bone marrow cells. Inverse correlation with cellular proliferation. J. Immunol. 149, 2179–2184.10.4049/jimmunol.149.6.2179Search in Google Scholar

Rakshit, S., Bagchi, J., Mandal, L., Paul, K., Ganguly, D., Bhattacharjee, S., Ghosh, M., Biswas, N., Chaudhuri, U., and Bandyopadhyay, S. (2009). N-acetyl cysteine enhances imatinib-induced apoptosis of Bcr- Abl+ cells by endothelial nitric oxide synthase-mediated production of nitric oxide. Apoptosis 14, 298–308.10.1007/s10495-008-0305-7Search in Google Scholar

Selleri, C., Maciejewski, J.P., Montuori, N., Ricci, P., Visconte, V., Serio, B., Luciano, L., and Rotoli, B. (2003). Involvement of nitric oxide in farnesyltransferase inhibitor–mediated apoptosis in chronic myeloid leukemia cells. Blood 102, 1490–1498.10.1182/blood-2003-01-0178Search in Google Scholar

Seth, P., Kumari, R., Dikshit, M., and Srimal, R.C. (1994). Modulation of rat peripheral polymorphonuclear leukocyte response by nitric oxide and arginine. Blood 84, 2741–2748.10.1182/blood.V84.8.2741.2741Search in Google Scholar

Shami, P.J. and Weinberg, J.B. (1996). Differential effects of nitric oxide on erythroid and myeloid colony growth from CD34+ human bone marrow cell. Blood 87, 977–982.10.1182/blood.V87.3.977.bloodjournal873977Search in Google Scholar

Shami, P.J., Moore, J.O., Gockerman, J.P., Hathorn, J.W., Misukonis, M.A., and Weinberg, J.B. (1995). Nitric oxide modulation of the growth and differentiation of freshly isolated acute non-lymphocytic leukemia cells. Leuk. Res. 19, 527–533.10.1016/0145-2126(95)00013-ESearch in Google Scholar

Swerdlow, S.H., Campo, E., Harris, N.L., Jaffe, E.S., Pileri, S.A., Stein, H., Theile, J., and Vardiman, J.W. (2008). WHO Classification of Tumours of Haematopoietic and Lymphoid Tissue, 4th ed., (Lyon, France: IARC).Search in Google Scholar

Taylor, E.L. and Megson, A.G. (2003). Nitric oxide: a key regulator of myeloid inflammatory cell apoptosis G. Cell Death Differ. 10, 418–430.10.1038/sj.cdd.4401152Search in Google Scholar PubMed

Thomsen, L.L., Scott, J.M.J., Topley, P., Knowles, R.G., Keerie, A.J., and Frend, A.J. (1997). selective inhibition of inducible nitric oxide synthase inhibits tumor growth in vivo: studies with 1400W, a novel inhibitor. Cancer Res. 57, 3300.Search in Google Scholar

Tripathi, A.K., Jain, M., Singh, A.K., Barthwal, M.K., Kumar, A., and Dikshit, M. (2012). Alteration in the circulating nitrite levels and expression of NOS isoforms in the neutrophils of AML patients. Blood 120, 4325.10.1182/blood.V120.21.4325.4325Search in Google Scholar

Tsumori, M., Tanaka, J., Koshimura, K., Kawaguchi, M., Murakami, Y., and Kato, Y. (2002). Cytotoxic effect of nitric oxide on human hematological malignant cells. Acta Biochim. Pol. 49, 139–144.10.18388/abp.2002_3830Search in Google Scholar

Ushmorov, A., Ratter, F., Lehmann, V., Dröge, W., Schirrmacher, V., and Umansky, V. (1999). Nitric oxide-induced apoptosis in human leukemic lines requires mitochondrial lipid degradation and cytochrome c release. Blood 93, 2342–2352.10.1182/blood.V93.7.2342Search in Google Scholar

Wallerath, T., Gath, I., Aulitzky, W.E., Pollock, J.S., Kleinert, H., and Forstermann, U. (1997). Identification of the NO synthase isoforms expressed in human neutrophil granulocytes, megakaryocytes and platelets. Thromb. Haemost. 77, 163–167.10.1055/s-0038-1655925Search in Google Scholar

Received: 2017-4-14
Accepted: 2017-6-2
Published Online: 2017-6-15
Published in Print: 2017-10-26

©2017 Walter de Gruyter GmbH, Berlin/Boston

Downloaded on 29.9.2025 from https://www.degruyterbrill.com/document/doi/10.1515/hsz-2017-0143/html
Scroll to top button