Role of glucocorticoids in myeloid leukemia cells

MICAELA SILBERMINS; ADALI PECCI; LUCIANA ROCHA VIEGAS

Mar del Plata

Congreso; LXI Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2016

Sociedad Argentina de Investigación Clínica (SAIC)

The main goal of this project is to study the role of glucocorticoids in RA-induced human promyelocytic leukemia cell differentiation. Undifferentiated HL60 cells were treated with RA in the presence or absence of Dex over 72h in medium containing steroid stripped serum. Our results showed that Dex markedly enhances a RA-induced cell differentiation response, observed as a potentiated expression of the cell surface marker CD11b by flow cytometry analysis (control: 1.54 % RA: 28.6 % RA+Dex: 38.1 %) and as the ability to reduce NBT. To gain functional insights into this differentiation process, the expression of hox genes, pscd4 and meis2 was monitored in RT-qPCR assays.Notably, upon 24h of combined treatment the up-regulation of hoxA3 expression was observed. Finally, the addition of Dex seems to potentiate RA-induced expression of hoxA3 and pscd4 genes after 48h of treatment, and the expression of hoxA4 gene after 72h. Overall, our data suggests the existence of a synergistic effect of Dex and RA on HL60 cell differentiation. Further characterization of this molecular context could thus be instrumental in defining a general molecular mechanism that identifies attractive targets for therapeutic strategies in myeloid leukemia.