Abstract 3120: B-Catenin gene expression and its mutations: promising and key component in the pathogenesis of acute myeloid leukemia (AML)

Abstract

Abstract INTRODUCTION AND AIM: Wnt signaling pathway plays a critical role in stem cell self-renewal and proliferation of leukemic stem cells and its association with the pathogenesis of acute myeloid leukemia (AML) has also been described. Beta-Catenin, a key regulator of Wnt signaling is highly expressed in cancers. Its role has been recently documented in AML however its prognostic significance in AML is not clear. The present study was carried to determine the potential prognostic implications of B-catenin expression and mutations in de novo AML patients. METHODS: We performed the gene expression of B-Catenin and its mutations analysis in exon 3. We investigated the expression of B-Catenin gene in bone marrow and/or blood samples by quantitative PCR using SYBR-Green chemistry and analysis was done by ΔΔCT Method. 18S RNA and B2M genes were used as reference genes. B-Catenin mutations analysis was by done direct DNA Sanger sequencing. RESULTS: Total 117 de novo non M3 AML patients and 40 healthy controls were included for the gene expression and analyzed for their clinicopathologic and prognostic significance. Median age for entire cohort (n = 117) was 17.0 years (Range 1-60 years) with male:female ratio of (1.8:1). FLT3-ITD mutation was positive in 11 (9.5%) patients. Only 4% of AML patients showed genetic alterations in exon 3 of B-catenin and no significant correlation with base line characteristics. B-catenin showed a significantly increased mRNA expression with a 5 fold rise as compared to healthy controls (p<0.05). B-catenin over expression was significantly associated with poor survival at median followup of 17 months and having less CR rates (p = 0.03). There was no significant correlation of B-catenin over expression vs baseline clinical characteristics like Hb, TLC, Platelets, Cyto group (p = 0.11), blast percentage (p = 0.28), Flt3-itd mutations (p = 0.42). CONCLUSION: These results provide the evidence for WNT signaling activation existence in AML patients and suggest that B-Catenin could be the key component in the pathogenesis and can be prognostically important marker in AML. However B-catenin expression in larger cohort of samples and with longer follow-up is required to confirm our findings. Citation Format: Mohsin Maqbool, Sobuhi Iqbal, Atul Sharma, Sameer Bakhshi, Sreenivas Vishnubhatla, Ashish Datt Upadhyay, Lalit Kumar. B-Catenin gene expression and its mutations: promising and key component in the pathogenesis of acute myeloid leukemia (AML). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3120.