Expression of circadian genes in lymphocytes in erythremia

Biological rhythms are important in the regulation of almost all aspects of the life of most organisms. Biological clock controls wide spectra both physiological and metabolic processes supporting energy balance, cyclic character of hormone secretion and immune response as well as cell proliferation. Circadian system of biological clock represents a complex program of tightly interconnected direct and feed-back pathways for supporting of metabolic homeostasis. Its dysregulation leads to development of various diseases. Biological rhythms are tightly interconnected with endoplasmic reticulum stress and play an important role in the regulation of immune system, especially in tumor growth. Moreover, alterations in BMAL1, PER1, and PER2 genes expression are related to tumor growth including development of acute myeloid leukemia. Thus, the aim of this study was investigation of the expression of key genes of biological clock in lymphocytes of patients with erythremia (рolycythemia vera), which is mostly prevalent myeloproliferative disease, in comparison to lymphocytes of healthy donors. The expression level of PER1, PER2, CLOCK, BMAL1, BMAL2, and CRY1 genes, which are the major components of biological clock in human and animals, were measured in blood lymphocytes of patients with erythremia in comparison to control (lymphocytes of healthy donors) using quantitative polymerase chain reaction in real time. It was shown that in lymphocytes of erythremia patients significantly increases the expression level of PER1 (almost in 2.5 fold), CLOCK (+42 %), BMAL1 (+19 %), BMAL2 (+16 %) and CRY1 (+27 %) mRNA as compared to lymphocytes of healthy donors. At the same time, the expression level of PER2 mRNA in lymphocytes of patients with erythremia significantly does not changed compared to healthy donors. Results of this study are shown significant dysregulations in the function of major circadian genes in lymphocytes of peripheral blood of patients with erythremia and may help to identify target genes for creation of new strategies for cancer treatment including erythremia.