Identification of novel therapeutic target molecules and the molecular mechanism for refractory multiple myeloma

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K19059
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pathological medical chemistry
• Research Institution: Keio University
• Principal Investigator: ICHIKAWA Daiju 慶應義塾大学, 薬学部(芝共立), 助教 (60462793)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: 多発性骨髄腫 / IMiDs

Outline of Final Research Achievements

In this study, we focused on the mechanism of IMiDs resistance in MM. We examined gene profiles in lenalidomide-sensitive and -resistant cell lines with or without lenalidomide using DNA microarray following GSEA and cluster analyses. In GSEA, P53 PATHWAY gene group is enriched in lenalidomide- treated sensitive MM cells as compared to resistant cell line. In cluster analyses, 50 spots were down-regulated and 132 spots were upregulated under lenalidomide-treated sensitive MM cells. In those genes, BNIP3, DCAF4L2, and STAP2 proteins are concordantly increased. We next attempted knockdown of BNIP3, DCAF4L2, and STAP2 in lenalidomide-sensitive cells using retroviral delivery of shRNA against human those genes. However those genes knockdown did not rescue lenalidomide-induced cell. We need to reveal that P53 PATHWAY gene group and another up- or down-regulated genes in cluster analyses regulated the sensitivity of MM cells to IMiDs in the future.

Free Research Field

がん免疫