Iron metabolism regulatory mechanisms in initial leukocytosis in patients with acute leukemia

Aim. To study levels of hepsidine (Hp), hypoxia-inducible factor-1alpha (HIF-1α), erythropoietin (EP) and ferritin in patients with acute leukemia (AL), effects of protein fractions of homogenate of blastic cells (BC) on regulatory proteins studied.
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.

acute leukemia, ferritin, hepsidin, hypoxia-inducible factor, erythropoietin