PB1893: THE STUDY OF SET GENE AND PROTEIN PHOSPHATASE 2A IN CHRONIC MYELOID LEUKEMIA AND THEIR ROLE IN DISEASE PROGRESSION

Abstract

Background: Chronic myeloid leukemia (CML) is characterized by three stages, chronic, accelerated and blastic phases. Tyrosine kinase inhibitors (TKIs) delay the progression of CML into blastic phase. However, resistance to TKIs has emerged due to different factors. Protein phosphatase 2A (PP2A) is a tumor suppressor protein that affect many cellular pathways. Inhibition of PP2A by PP2A inhibitors such as SET is one mechanism responsible for CML progression. Moreover, phosphorylation of C-terminal tyrosine residue (Tyr307) on the PP2A catalytic subunit was associated with decreased protein activity and consequently, loss of its tumor suppression function. Aims: This work studied the role of SET gene expression as well as phosphorylated PP2A expression in CML progression Methods: The study included 50 CML patients under TKI therapy for at least 18 months, and 50 healthy controls. All study participants were tested for SET gene expression level in peripheral blood by RQ-PCR and PP2A (Tyr307) in serum by ELISA. Moreover, patients were analyzed for complete blood count, BCR-ABL1 in peripheral blood by RQ-PCR and bone marrow examination. Results: High SET gene expression in patients was found to be significantly associated with advanced disease phase and worse clinical and laboratory findings while low expression was significantly associated with better molecular response assessed by BCR-ABL1 level. High levels of PP2A (Tyr307) was significantly associated with blastic phase. Moreover, significant positive correlations was found between BCR-ABL1 level and both SET gene expression and PP2A Tyr307 levels. Image:Summary/Conclusion: SET gene and PP2A are important factors in CML progression and can be used as possible targets for treatment in TKI-resistant cases.