Abstract
This experimental study was conducted in bone marrow (BM) samples collected from 25 patients with newly diagnosed ALL. In addition, we cultured the RPMI-8402, Jurkat, Ramos, and Daudi cell lines and assessed the effects of internal (hypoxia) and external (chemotherapy medications L-asparaginase [ASP] and vincristine [VCR]) factors on h19 expression. The expressions of H19, P53, c-Myc, HIF-1α and β-actin were performed using quantitative real-time polymerase chain reaction (qRT-PCR) method. There was significantly increased H19 expression in the B-cell ALL (B-ALL, P<0.05), T-cell ALL (T-ALL, P<0.01) patients and the cell lines. This upregulation was governed by the P53, HIF-1α, and c-Myc transcription factors. We observed that increased c-Myc expression induced H19 expression; however, P53 adversely affected H19 expression. In addition, the results indicated that chemotherapy changed the gene expression pattern. There was a considerable decrease in H19 expression after exposure to chemotherapy medications; nonetheless, hypoxia induced H19 expression through P53 downregulation. Our findings suggest that H19 may have an important role in pathogenesis in ALL and may act as a promising and potential therapeutic target.
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