Investigation of long non coding rnas effective on cell proliferation, cell differentiation and apoptosis in de novo adult patients with acute myeloid leukemia

Long non-coding RNAs (lncRNA) are RNAs longer than 200 nucleotides that have no protein-coding potential and function as regulators. The importance of lncRNAs in disease prognosis has been reported in relation to many diseases and cancers, and they have been suggested as biomarkers in some types of cancer. Acute myeloid leukemia (AML) is the cancer of hematopoietic cells with various genetic abnormalities that cause abnormal proliferation, differentiation, survival of myeloid progenitor cells. It is the most common type of leukemia in adults. Genetic background is important in AML disease. The heterogeneity of the disease limits complete elucidation of its molecular mechanism. Our study, the hox transcript antisens intergenic RNA (HOTAIR) in the elucidation of the molecular mechanisms of AML, H19, colon cancer associated transcript 1 (CCAT1) gastric carcinoma proliferation enhancing transcript 1 (GHET1), which increases proliferation of gastric carcinoma, and v-Myelocytomatosis viral oncogen homologous (c-MYC) and Ras, which are associated with these lncRNAs expression levels of protein 2B (RAP2B) were investigated. The effect of lncRNAs on the cell cycle by the expression cyclin-dependent kinase 4 (CDK4) and its effect on apoptosis by the expression Bcl-2-related X protein (BAX) were investigated. In our research, real-time polymerase chain reaction (PCR) method was used to determine expression levels. All results were evaluated by clinical conditions and genetic variations of the patients. Since we did not find any information on the difference between the expression rates of the lncRNAs we investigated in blood and bone marrow samples in AML, we first compared their expression levels in AML blood and bone marrow samples. The difference between the expression levels of HOTAIR, H19, CCAT1, GHET1, c-MYC, RAP2B, BAX and CDK4 in AML blood and bone marrow samples was not statistically significant (p>0.05). It was found that the expression HOTAIR and H19 were high in AML patients compared to healthy controls (p<0.05). The expression of HOTAIR was increased in AML patients carrying the NPM1 variant compared to wild-type patients (p<0.05). Expression levels of c-MYC and CDK4 were found to be higher in AML patients compared to healthy controls (p<0.05). The expressions of CCAT1, GHET1 and BAX were not statistically significant (p>0.05). The expression of RAP2B in AML patients was low than in healthy controls (p<0.05). H19 expression rates were positively correlated with c-MYC expression, monocyte levels, leukocyte levels, and blast percentages. There was a positive relationship between the expression rates of HOTAIR, H19, GHET1, CCAT1 and CDK4. When our results are evaluated together; results of HOTAIR, H19, GHET1, CCAT1, c-MYC, RAP2B, CDK4, and BAX obtained from bone marrow samples of patients with AML were comparable to results obtained from blood of healthy controls. In AML, the expression levels of HOTAIR, H19, GHET1, CCAT1 may play a role in leukemogenesis by contributing to the progression of the cell cycle through the increase in CDK4 gene expression, which is positively related. Our results need to verify with larger sample groups in AML. In light of these findings, HOTAIR and H19 can be used as a potential biomarker.