Abstract 1603: Highly expressed integrin-α8 in multiple myeloma early relapse induces epithelial to mesenchymal transition-like features

Abstract

Abstract Multiple myeloma (MM) is characterized by clonal proliferation of malignant plasma cells in the bone marrow niches. Despite the remarkable advances of treatment for MM,still many patients of MM struggle early relapses and its mechanism is not well understood. Patients with early relapse after autologous bone marrow transplantation need to be biologically characterized to better understand and reach complete remission. To define altered gene expression in MM relapse, we performed microarray with whole bone marrow aspirates from 16 relapsed MM patients who underwent auto-BMT. Gene expression profile was compared (P < 0.01) and divided into two groups on the basis of their progression-free survival (PFS) at the point of 12 months. To discern the significance of the result, only four patients with shortest and longest duration of PFS was also nexamined, and interestingly both of the analysis showed common up-regulated genes including PDGFB, ITGA7, and ITGA8. Their associated pathways were focal adhesion, ECM-receptor interaction, and regulation of actin cytoskeleton (P < 0.05). By performing qRT-PCR, we validated three genes and only ITGA8 was corresponded with microarray data that early relapsed patients showed higher expression of ITGA8. Several integrin family members are well documented to involve in MM progression that it mediates MM cell adhesion, migration and homing through BM microenvironment. However, integrin-α8 is largely unknown in MM. Due to ITGA8 was highly expressed in MM relapse, we functionally overexpressed integrin-α8 in MM cell lines. Surprisingly, it activated genes showing stem-like features including HIF1a, VEGF, OCT4, and Nanog and EMT-related genes, such as N-cadherin, Slug, Snail and CXCR4. These, consequently enhanced invasion and migration abilities and reduced adhesion activity, indicating the mechanism of MM progression, metastasis as well as relapse. Our speculated specific gene, integrin-α8, up-regulated in MM early relapse, regulates EMT feature in MM that suggesting a potential marker for relapse and attractive clinical target to achieve complete remission. Citation Format: Jiyeon Ryu, Youngil Koh, Hyun Jung Lee, Hyun Sub Chung, Sung-Soo Yoon. Highly expressed integrin-α8 in multiple myeloma early relapse induces epithelial to mesenchymal transition-like features. [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 1603.