Email this article Regulatory mechanisms of iron metabolism in patients with acute leukemia
- Authors: Makeshova A.B.1, Levina A.A.1, Mamukova Y.I.1, Savchenko V.G.1, Makeshova AB1, Levina AA1, Mamukova Y.I1, Savchenko VG1
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- Issue: Vol 81, No 7 (2009)
- Pages: 16-20
- Section: Editorial
- URL: https://ter-arkhiv.ru/0040-3660/article/view/30352
- ID: 30352
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Abstract
Material and methods. Thirty eight patients with newly diagnosed acute leukemia (AL) were divided into three groups by anemia severity: group 1 (Hb > 90 g/l), group 2 (Hb 90-70 g/l), group 3 (Hb < 70 g/l). Erythropoietin concentration was measured with enzyme immunoassay, serum ferritin (SF) - by radioimmunoassay; HIF-1alpha, hepsidine - by sandvich enzyme immunoassay with use of monospecific antisera and monoclonal antibodies against relevant antigens.
Results. In AL patients SF before treatment was 10 times higher than in healthy subjects, administration of cytostatics elevated this concentration even more. Hepsidine and HIF-1alpha are also elevated. Treatment reduces hepsidine level twice in all the groups. This may be due to reduction of the tumor mass. Erythropoietin was 20-35 times higher in all the patients, especially in myelotoxic agranulocytosis (up to 1000 mU/ml) with reduction after recovery of hemopoiesis (in some patients to normal values 20-30 mU/ml). Hepsidine and HIF-1alpha concentrations were also maximal in myelotoxic agranulocytosis (20-28 pg/ml). After recovery of hemopoiesis these values fell to initial values 7-9 pg/ml). Transfusion of donor erythrocytic mass normalized HIF-1alpha concentration and decreased that of hepsidine. Its elevation and high HIF-1alpha were observed after the transfusion in 17% patients.
Conclusion. Disorders in regulatory mechanisms in AL patients throughout the observation confirm the role of the proteins studied in homeostasis. Changes in HIF-1alpha and hepsidine concentrations can be used as indicators of transfusion efficacy.
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About the authors
Aynura Bekbolotovna Makeshova
Email: ainuramak@mail.ru
Alla Arkad'evna Levina
Yuliya Iosifovna Mamukova
Email: hloe@rambler.ru
Valeriy Grigor'evich Savchenko
Email: svg.@blood.ru
A B Makeshova
A A Levina
Yu I Mamukova
V G Savchenko
References
- Leong W., Lonnerdal B. Hepcidin the recently identified peptid that appears to regulate iron absorption. J. Nutr. 2004; 134: 1-4.
- Ganz T. Hepcidin and its role in regulating systemic iron metabolism. Hematology 2006; 11: 29-35.
- Semenza G. L. HIF-1 and human disease: one highly involved factor. Genes Dev. 2000; 14: 1983-1991.
- Nemeth E., Rivera S., Gabayan V. et al. IL-6 mediates hypoferremia inflammation inducing the synthesis of the iron regulatory hormone hepcidin. J. Clin. Invest. 2004; 113: 1271-1276.
- Yoon D., Pastore Y. D., Divoky V. et al. Hypoxia-inducible factor 1 deficience results in dysregulated erythropoiesis signaling and iron homeostasis in mouse development. J. Biol. Chem. 2006; 281: 25703-25711.
- Haase V. H. The VHL tumor suppressor in development and disease: functional studies in mise by conditional gene targeting. Semin. Cell. Dev. Biol. 2005; 16: 564-574.
- Carroll V. A., Ashcroft M. Role hypoxia-inducible factor (HIF)-1α versus HIF-2α in the regulation of HIF target genes in response to hypoxia, insulin-like growth factor-1 or loss of von Hippel-Lindau function: implicatins for targeting the HIF pathway. Cancer Res. 2006; 66 (12): 6264-6270.
- Haase V. H. Hypoxia-inducible factors in the kidney. Am. J. Physiol. Renal Physiol. 2006; 291: F271-F281.
- Hirota K., Semenza G. L. Regulation of angiogenesis by hypoxia-inducible factor 1, Crit. Rev. Oncol. Hematol. 2006; 59: 15-26.
- Maxwell P. H., Wiesener M. S., Chang G. W. et al. The tumor suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature 1999; 399: 271-275.
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