International Journal of Hematology and Oncology
2023, Vol 33, Num 4 Page(s): 063-071
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The Role of NOL7 in All-Trans Retinoic Acid-Induced Acute Promyelocytic Leukemia Cells
Zeliha EMRENCE1, Melda SARIMAN1, Neslihan ABACI1, Suzan CINAR2, Burcu SALMAN1, Nezahat Ece BIBEROGLU1, Aris CAKIRIS1, Gunnur DENIZ2, Sema Sirma EKMEKCI1
1Istanbul University, Aziz Sancar Institute of Experimental Medicine, Department of Genetics
2Istanbul University, Aziz Sancar Institute of Experimental Medicine, Department of Immunology, Istanbul, TURKEY
Keywords: Acute myeloid leukemia, ATRA resistance, Granulocytic differentiation, NOL7, PML-RARA
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.
Zeliha EMRENCE1, Melda SARIMAN1, Neslihan ABACI1, Suzan CINAR2, Burcu SALMAN1, Nezahat Ece BIBEROGLU1, Aris CAKIRIS1, Gunnur DENIZ2, Sema Sirma EKMEKCI1
1Istanbul University, Aziz Sancar Institute of Experimental Medicine, Department of Genetics
2Istanbul University, Aziz Sancar Institute of Experimental Medicine, Department of Immunology, Istanbul, TURKEY
Keywords: Acute myeloid leukemia, ATRA resistance, Granulocytic differentiation, NOL7, PML-RARA
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.
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