VITAMIN E ACTIVATES EXPRESSION OF C/EBP ALPHA TRANSCRIPTION FACTOR AND G-CSF RECEPTOR IN LEUKEMIC K562 CELLS

Abstract

Chronic myeloid leukemia (CML) is a clonal hematopoietic stem cell disorder associated with the activity of BCR-ABL fusion oncogene. Tyrosine kinase inhibitors are the current treatment of CML, but secondary mutations finally contribute to therapy resistance and blast crisis of the disease. The search for the novel compounds for the effective control of CML is now in the spotlight. The progression of CML to blast crisis is correlated with down-modulation of C/EBP alpha. Therefore, C/EBP alpha may be considered as a putative target in differentiation therapies in myeloid leukemias. The aim of the study was to assess the potential of vitamin E as the possible inducer of C/EBP alpha expression in BCR-ABL-positive CML K562cells. RNA extracted from K562cells cultured with valproic acid or vitamin E was converted to cDNA, RT-PCR reactions were carried out using HotStarTaq DNA polymerase with primers for C/EBP alpha and granulocyte colony-stimulating factor receptor (G-CSFR). We have not found detectable expression of C/EBP alpha in K562cells. Upon 48-h culture with vitamin E at a dose of 100µM, K562cells expressed both C/EBP alpha and G-CSFR. VitaminE restored the expression of C/EBP alpha mRNA in chronic myelogenous leukemia K562cells. In this setting, G-CSFR expression in vitaminE treated K562cells seems to suggest the activation to granulocytic differentiation. It should be further elucidated whether such effects of vitamin E on C/EBP alpha transcription factor are direct or mediated indirectly due to antioxidant properties of vitamin E.