本研究では多発性骨髄腫におけるレナリドミド感受性株及び抵抗性株についてDNA microarrayより遺伝子発現量の差異をGSEA, クラスタリング解析を行った。その結果, それぞれレナリドミド処理のみでエンリッチされたものはP53 PATHWAY群のみ, レナリドミド感受性株で刺激依存的に減少するものとして50 spots, 刺激依存的に上昇するものとして132 spotsが得られた。そのうちタンパク質発現について同様の変動があったものとしてBNIP3, DCAF4L2, STAP2が得られた。
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.

研究種目 : 若手研究(B)
研究期間 : 2016～2017
課題番号 : 16K19059
研究分野 : がん免疫