International Journal of Myeloma
Online ISSN : 2187-3143
10 巻, 1 号
選択された号の論文の3件中1~3を表示しています
ORIGINAL
  • Mariko ISHIBASHI, Keima UEDA, Yoichi IMAI, Koiti INOKUCHI, Rimpei MORI ...
    原稿種別: ORIGINAL
    2020 年 10 巻 1 号 p. 1-7
    発行日: 2020年
    公開日: 2022/07/06
    ジャーナル フリー

    The Notch signaling pathway plays a crucial role in the tumor microenvironment. We examined the expression of Notch receptors (Notch1, Notch2, Notch3, and Notch4) and its ligands (JAG1, JAG2, DLL1, DLL3, and DLL4) in multiple myeloma (MM) cells and the functions of Notch signaling in disease progression. NOTCH1, NOTCH2, and JAG1 mRNA were highly expressed in 17 MM cell lines and primary MM cells from 28 patients, although mRNA levels of NOTCH1 were significantly lower than those of NOTCH2. However, anti-Notch1 antibody inhibited MM cell proliferation and increased the percentage of bortezomib-induced apoptotic MM cells as compared with isotype control and cells cultured with anti-Notch2 antibody. Furthermore, Notch1+ MM cells showed greater proliferative potential and decreased drug susceptibility compared with Notch cells. Aggressive disease behaviors in Notch1+ MM cells were suppressed by anti-JAG1 antibody. Furthermore, gene expression in Notch1+ cells showed upregulation of p21 and CCND1/2 and downregulation of apoptotic genes compared with those in Notch cells. Those results demonstrate that the Notch1–JAG1 signaling pathway confers a high malignant potential, suggesting that its Notch signaling may be specifically associated with MM disease progression.

CASE REPORT
  • Kengo UDAKA, Shingen NAKAMURA, Shiro FUJII, Ryosuke MIYAMOTO, Naoko MA ...
    原稿種別: CASE REPORT
    2020 年 10 巻 1 号 p. 8-12
    発行日: 2020年
    公開日: 2022/07/06
    ジャーナル フリー

    We herein describe a 52-year-old man with multiple myeloma (MM) who developed progressive multifocal leukoencephalopathy (PML). He was diagnosed with MM in December 20XY, and underwent high-dose chemotherapy followed by autologous stem cell transplantation. He relapsed in October 20XY+2, and he was treated with the oral administration of cyclophosphamide and prednisolone (CP). He developed apraxia and visual disturbance in March 20XY+4. Since PML was suspected, we stopped CP and mirtazapine was initiated; however, his neurological symptoms did not improve. He was diagnosed with PML based on John Cunningham virus (JCV) DNA in his cerebrospinal fluid (CSF). He was treated with therapy involving of mirtazapine, cytarabine, and high-dose immunoglobulin; however, his neurological disorders did not improve despite the disappearance of JCV DNA in his CSF. Therefore, we started combination therapy of mirtazapine and mefloquine, which resulted in the ­significant improvement of both his neurological symptoms and MRI findings. Although we restarted the anti-MM treatment, his neurological symptoms remained stable for more than 2 years with the continuation of this com­bination therapy. The present case suggests that combination therapy of mirtazapine and mefloquine is effective for patients with PML, particularly those requiring immunosuppressive chemotherapy.

REVIEW
  • 池田 翔, 田川 博之
    2020 年 10 巻 1 号 p. 13-19
    発行日: 2020年
    公開日: 2022/07/06
    ジャーナル フリー

    多発性骨髄腫は難治性の形質細胞腫瘍であり,その治療法について多くの研究者が精力的に検討を進めてきた。新たな治療標的として,骨髄微小環境の様々な要素が考慮される。この中で低酸素応答は細胞の恒常性を保つための重要なプロセスであり,多発性骨髄腫を含むがん一般的に治療標的として検討されている。骨髄の酸素分圧は50~55 mmHgであるのに対し,低酸素ニッチは10 mmHg未満と想定されている。低酸素ニッチに適応する骨髄腫細胞は,低酸素誘導因子HIFを介した遺伝子発現変化を起こし治療抵抗性を獲得している。ただしHIFの阻害は正常細胞や組織への悪影響が懸念され臨床応用はいまだ困難であるため,その標的分子の機能解析が必要である。特に,低酸素応答が誘導する代謝経路の変化,播種,骨髄環境の悪性化などは有望な治療標的になりうる。今後,低酸素環境や低酸素誘導性遺伝子を標的とした治療薬の実用化が期待される。

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