Determination of expression levels of relapse-related genes at the time of diagnosis in childhood B precursor cell acute lymphoblastic leukemia

Objective: While approximately 85% of childhood precursor B-ALL cases go into remission with a good response to treatment, relapse is observed in 15% of cases leading to death. Level changes in the expression of some genes found to be associated with resistance to treatment and survival in B-ALL. We aimed to determine whether there is a change in the expression levels of relapse-related AURKA, CASP1, GPM6B, NUDT15, S100A8 and Survivin genes which cannot be determined by conventional cytogenetic and molecular cytogenetic methods in childhood pre-B ALL cases at the time of diagnosis. With this study, in order to determine the relapse risk, it is aimed to identify candidate biomarkers, via analysing the change in the expression level of indicated genes. Method: cDNA synthesis had been performed following RNA isolation from bone marrow aspiration materials of 15 childhood cases with Pre-B ALL at the time of first diagnosis and from bone marrow aspiration materials of 5 healthy bone marrow donors. mRNA expression levels of AURKA, CASP1, GPM6B, NUDT15, S100A8 and Survivin genes; and additionally as a "housekeeping" gene levels of the β-Actin gene had been investigated using Quantitative Real Time-PCR (qRT-PCR) method. The findings obtained as a result of qRT-PCR analysis had been statistically analyzed using Shapiro-Wilk and Kolmogorov Smirnov Z test. Results: As a result of this study, statistically significant increase had been found in the mRNA expression levels of AURKA (p<0.05), CASP1 (p<0.05) and Survivin (p<0.05) genes compared to the healthy group with 2-ΔΔCT analysis, which is the commonly preferred method. While there was an increase in ΔCT values, a statistically significant difference was determined only in the Survivin gene. In the GPM6B, NUDT15 and S100A8 genes, there was no statistically significant difference in mRNA expression levels both in terms of ΔCT values and 2-ΔΔCT analysis. Conclusion: The detection of statistically significant differences in the expression levels of AURKA, CASP1 and Survivin genes with 2-ΔΔCT analysis in childhood pre-B ALL cases suggests that these three genes can be used as biomarkers at the time of diagnosis to determine the risk of relapse. Key words: childhood precursor B-ALL, relapse, relapse-associated genes, qRT-PCR