Uhod-Uluslararasi Hematoloji-Onkoloji Dergisi, vol.30, no.2, pp.63-71, 2020 (Journal Indexed in SCI Expanded)
The promyelocytic leukemia-retinoic acid receptor alpha (PML-RARA) fusion gene is present in 98% of the patients with acute promyelocytic leukemia (APL), the M3 subtype of acute myeloid leukemia (AML). All-trans retinoic acid (ATRA) is widely used to treat patients
with APL. Nucleolar Protein 7 (NOL7) is a tumor suppressor gene regulated by retinoid X receptor (RXR). The 6p23 chromosomal
region, where NOL7 is located, is associated with many cancers, including AML. Here, we aimed to investigate the effect of NOL7 in
two AML cell lines (the PML-RARA-positive NB4 cell line and the PML-RARA-negative HL60 cell line) and in the resistance to ATRA.
For this purpose, we knocked down NOL7 expression by using short interfering RNA (siRNA) and stimulated the cells with ATRA.
Apoptosis, cell viability, proliferation, and granulocytic differentiation analyses were performed. Our findings show that granulocytic differentiation was blocked in ATRA-treated NB4 cells 24 hours after NOL7 siRNA transfection when the expression of NOL7 had been
reduced by 81%. Downregulation of NOL7 had no apparent effect on the cellular proliferation and apoptosis. Our study suggests that
ATRA-induced granulocytic differentiation is inhibited in NOL7-downregulated NB4 cells. These results suggest that NOL7 expression
contributes to ATRA-induced granulocytic differentiation and loss of NOL7 might be involved in the development of ATRA resistance.