PB1647 EXPRESSION OF PHOSPHORYLATED AKT AND CLASS I PI3K ISOFORMS IN CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA

Background : Acute lymphoblastic leukemia (ALL) is the most common neoplastic disease in children and represents 30% of all childhood malignancies. Although more than 80% of ALL cases are long term survivors, there is still a percentage of resistant or relapsed disease. The identification of genes and molecular pathways that are involved is crucial for targeted therapy design. The intracellular signaling pathway PI3K/AKT gets induced by growth factors and plays an important role in triggering many biological processes of the cell such as cell growth, metabolism, proliferation, survival, metabolism of insulin, protein synthesis and apoptosis. Recently it has been found that changes in the expression and mutations in many molecules of that pathway are involved in tumor genesis, which makes them an attractive target for cancer therapy. Aims: The study of the expression of the P110β, P110δ and P‐Akt proteins in leukemic blasts of bone marrow from children with ALL at diagnosis and lymphomononuclear cells from children in remission, compared to the expression in lymphomononuclear cells from bone marrow of children with solid tumors without marrow involvement. Methods: Bone marrow mononuclear cells from 31 children with ALL at diagnosis, 25 children with ALL in remission and 20 children with solid tumors without bone marrow involvement was collected. Proteins were extracted and were analyzed with Western blot. The detection of P‐Akt, P110β and P110δ was done with Thermo Scientific™ Pierce™ ECL Western Blotting Substrate,.The analysis of the results was performed with Image Lab and the statistical analysis with IBM SPSS Statistics version 25 (Kruskal‐Wallis test and Mann‐Whitney test). Results: The expression level of P‐Akt in ALL diagnosis was significantly lower compared with ALL in remission (0.66 ± 0.21 vs 1.97 ± 0.41, p = 0.004) as well as with the solid tumors without bone marrow involvement (0.66 ± 0.21 vs 1.03 ± 0.25, p = 0.019). Additionally, the expression of P110δ estimated significantly lower in ALL diagnosis compared with ALL remission (0.92 ± 0.37 vs 1.52 ± 0.41, p = 0.012). On the other hand, there was no statistically significant difference of P110β expression values between ALL diagnosis, remission and solid tumors. Summary/Conclusion: P‐Akt and P110δ expression was estimated decreased in ALL diagnosis although P110β expression was not found to be different between ALL diagnosis, ALL remission and solid tumors. Further studies are needed in order to clarify the relation of these proteins’ expression with other established prognostic factors and their role to the leukemia course, outcome and prognosis.