Abstract 2021: Integrin-alpha 8 as a potential therapeutic target in multiple myeloma early relapse

Abstract

Abstract Introduction: Multiple myeloma (MM) is an incurable neoplastic plasma cell disorder and many studies about MM biologic complexity have been reported. Despite the advances of treatment for MM, still many patients of MM exhibit early relapses and the mechanism of MM relapse is not well understood Patient with early relapse after autologous bone marrow transplantation need to be biologically characterized to better understand and reach complete remission. Materials and Methods: To define altered gene expression and pathways, we performed microarray with bone marrow from 16 relapsed MM patients who underwent autologous bone marrow transplantation. Gene expression profile was compared (P < 0.01) in 16 MM patients divided into two groups on the basis of their progression-free survival (PFS) at the point of 12 months or only four patients with shortest and longest duration of PFS. Results: 77 genes over two fold up-regulated were identified and inputted in pathway enrichment analysis. To ascertain of the result, only four patients with shortest and longest duration of PFS were examined with same way of analysis that 163 genes over two fold up-regulated were inputted in KEGG pathway database. Interestingly, both of the analysis showed common up-regulated Integrin-α8 (ITGA8) and its associated pathway, ECM receptor interaction and focal adhesion, was identified (P < 0.05). Several integrin family members are well documented to involve in MM disease progression but ITGA8 in MM is largely unknown. Functionally, we have investigated ITGA8 in MM cell lines that ITAG8 mediates MM cell adhesion, migration and drug resistance through bone marrow microenvironment which is regarded as leading events of MM relapse. Furthermore, its expression in MM is correlated with poor survival outcomes after autologous bone marrow transplantation. Conclusion: Our study demonstrated that gene expression in MM patients showed distinctly different pattern between early relapse and late relapse. Additionally, our speculated specific gene up-regulated in early relapse in MM, ITGA8, is a potential prognostic marker and suggests attractive target for future research. Citation Format: Jiyeon Ryu, Youngil Koh, Hyun Jung Lee, Hyun Sub Chung, Sung-Soo Yoon. Integrin-alpha 8 as a potential therapeutic target in multiple myeloma early relapse. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2021. doi:10.1158/1538-7445.AM2015-2021