Study of PI3/AKT signaling pathway role in Acute myeloid Leukemia through assessment of long non-coding RNAs, GAS6-AS1 and TINCR expression

Abstract

Background Acute myeloid leukemia (AML) involves genetic and epigenetic changes that have a pivotal role in cancer progression. The PI3K/AKT pathway is involved in AML pathogenesis, including drug resistance, making it a possible diagnostic marker and a potential target for new treatments. Patients and methods Our study tested the impact of the long noncoding RNAs, growth-arrest-specific antisense RNA1 (GAS6-AS1) and tissue differentiation-induced non-coding RNA (TINCR) on the PI3K/AKT signaling pathway. We included 50 AML patients and 50 controls with nonhematological malignancies from July 2019 to January 2022 at Alexandria Main University Hospital’s hematology department. Risk evaluation, including karyotyping, FLT3 and Nucleophasmine mutation analyses was conducted according 2022 European Leukemia Net standards. Patients were followed-up for 12 months after diagnosis. Results GAS6-AS1 was significantly overexpressed in AML cases. Receiver operating characteristic curve showed levels above 2.69 to be AML cases (area under the curve = 0.829, sensitivity 70%, specificity 92%). In addition, GAS6-AS1 expression correlated significantly with long-term prognosis beyond consolidation therapy in AML. However, it did not affect the response to induction therapy. In contrast, TINCR expression was similar in AML patients (2.40±3.18) and controls (2.89±3.05), indicated its limited role in AML pathogenesis. Conclusions Our findings support that GAS6-AS1 overexpression is closely linked to AML and may enhance treatment effectiveness, particularly in consolidation phase. On the other hand, TINCR appears to have no impact of AML tumorigenesis, indicating it has a limited potential as a therapeutic target in AML.