Iron metabolism regulatory mechanisms in initial leukocytosis in patients with acute leukemia
- Authors: Makeshova A.B.1, Levina A.A.1, Mamukova Y.I.1, Parovichnikova E.N.1, Savchenko V.G.1, Makeshova AB2, Levina AA2, Mamukova Y.I2, Parovichnikova EN2, Savchenko VG2
-
Affiliations:
- Hematological Research Center, Moscow
- Issue: Vol 83, No 10 (2011)
- Pages: 22-27
- Section: Editorial
- Submitted: 10.04.2020
- Published: 15.10.2011
- URL: https://ter-arkhiv.ru/0040-3660/article/view/30906
- ID: 30906
Cite item
Full Text
Abstract
Material and methods. Depending on leukocyte count in the onset of AL, 70 patients with first ever diagnosed AL were divided into two groups: group 1 - 17 patients with leukocyte count > 30109/l, group 2 - 53 patients with leukocyte count < 30109/l. Serum and leukocyte parameters were studied before treatment, during the treatment with cytostatic drugs, in the course of myelotoxic agranulocytosis (MTA), after normalization of hemograms. EP was detected with enzyme immunoassay, serum and leukocyte ferritin - with radioimmunoassay; HIF-1α, Hp - sandwich enzyme immunoassay using monospecific antisera and monoclonal antibodies against relevant antigens. Leukocytes were isolated in ficol and verografin solutions density gradient. Chromatographic division of the protein fractions in 3 patients with leukocytosis in AL onset and leukocytes of 3 donors was made by the method of preparative isoelectrofocusing of BC and leukocytes on LKB colon (Sweden). Effects of these fractions were studied on 11 plasma samples from hematological patients and 4 plasma samples from patients with normal hemopoiesis.
Results. Leukocytosis patients with initial AL have serum ferritin, Hp and HIF-1α levels about 2-5 times lower than patients without leukocytosis. Cytostatic treatment raises an HIF-1α level in BC about 15-fold (85.8±24.5 pg/ml), in the study group - 3-fold (15.2±3.3 pg/ml). The highest EP levels were seen in MTA. It is detected that protein fractions isolated from leukocytes of patients with leukocytosis in the disease onset raise HIF-1α content irrespective of HIF-1α presence in the fraction. Patients free of hematological diseases have no changes of the above proteins.
Conclusion. Great difficulties exist in ferritin and Hp levels between AL patients with leukocytosis in the onset of the disease and without of leukocytosis. The study of leukocytes suggests that tumor cells of such patients contain compounds which can regulate production of HIF-1α, Hp and ferritin.
Keywords
About the authors
Aynura Bekbolotovna Makeshova
Email: ainuramak@mail.ru
Alla Arkad'evna Levina
Email: yullevina@yandex.ru
Yuliya Iosifovna Mamukova
Email: julli72@mail.ru
Elena Nikolaevna Parovichnikova
Email: elenap@blood.ru
Valeriy Grigor'evich Savchenko
Email: svg@blood.ru
A B Makeshova
Hematological Research Center, MoscowHematological Research Center, Moscow
A A Levina
Hematological Research Center, MoscowHematological Research Center, Moscow
Yu I Mamukova
Hematological Research Center, MoscowHematological Research Center, Moscow
E N Parovichnikova
Hematological Research Center, MoscowHematological Research Center, Moscow
V G Savchenko
Hematological Research Center, MoscowHematological Research Center, Moscow
References
- Abdel-Wahab O., Levine R. L. Metabolism and the leukemic stem cell. J. Exp. Med. 2010; 207: 4677-4680.
- Roy C. N. Anemia of inflammation. In: Hematology. American Society of Hematology education program book. Washington; 2010. 276-280.
- Callens C., Coulon S. Targeting iron homeostasis induces cellular differentiation and synergizes with differentiating agents in acute myeloid leukemia. J. Exp. Med. 2010; 207: 4731- 4750.
- Vanasse G. J., Berliner N. Anemia in elderly patients: An emerging problem for the 21st century. In: Hematology American Society of Hematology education program book. Washington; 2010: 271-275.
- Young B, Zaritsky J. Hepsidin for clinicians. Clin. J. Am Soc. Nephrol. 2009; 4(8); 1384-1387.
- Li H., Ginzburg Y. Z. Crosstalk between iron metabolism and erythropoiesis. Advanc. Hematol. 2010; 2010: Article ID 605435. Epub. 2010. Jun 10.
- Ganz T. Hepcidin and its role in regulating systemic iron metabolism. Hematology 2006; 11: 29-35.
- Zhang J., Song L. P., Huang Y., Zhao Q. Accumulation of hypoxia-inducible factor-1 alpha protein and its role in the differentiation of myeloid leukemic cells induced by all-trans retinoic acid. Haematologica 2008; 93(10); 1480-1487.
- Hatfield K. J., Bedringsaas S. L., Ryningen A. Hypoxia increases HIF-1α expression and constitutive cytokine release by primary human acute myeloid leukaemia cells. Eur. Cytokine Netw. 2010; 21(3); 154-164.
- Peyssonnaus C., Zinkernagel A. S., Schuepbach R. A. et al. Regulation of iron homeostasis by the hypoxia-inducible transcription factors. J. Clin. Invest. 2007; 117(7): 1926-1932.