論文

国際誌
2022年1月12日

Eliminating chronic myeloid leukemia stem cells by IRAK1/4 inhibitors.

Nature communications
  • Yosuke Tanaka
  • Reina Takeda
  • Tsuyoshi Fukushima
  • Keiko Mikami
  • Shun Tsuchiya
  • Moe Tamura
  • Keito Adachi
  • Terumasa Umemoto
  • Shuhei Asada
  • Naoki Watanabe
  • Soji Morishita
  • Misa Imai
  • Masayoshi Nagata
  • Marito Araki
  • Hitoshi Takizawa
  • Tomofusa Fukuyama
  • Chrystelle Lamagna
  • Esteban S Masuda
  • Ryoji Ito
  • Susumu Goyama
  • Norio Komatsu
  • Tomoiku Takaku
  • Toshio Kitamura
  • 全て表示

13
1
開始ページ
271
終了ページ
271
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/s41467-021-27928-8

Leukemia stem cells (LSCs) in chronic myeloid leukemia (CML) are quiescent, insensitive to BCR-ABL1 tyrosine kinase inhibitors (TKIs) and responsible for CML relapse. Therefore, eradicating quiescent CML LSCs is a major goal in CML therapy. Here, using a G0 marker (G0M), we narrow down CML LSCs as G0M- and CD27- double positive cells among the conventional CML LSCs. Whole transcriptome analysis reveals NF-κB activation via inflammatory signals in imatinib-insensitive quiescent CML LSCs. Blocking NF-κB signals by inhibitors of interleukin-1 receptor-associated kinase 1/4 (IRAK1/4 inhibitors) together with imatinib eliminates mouse and human CML LSCs. Intriguingly, IRAK1/4 inhibitors attenuate PD-L1 expression on CML LSCs, and blocking PD-L1 together with imatinib also effectively eliminates CML LSCs in the presence of T cell immunity. Thus, IRAK1/4 inhibitors can eliminate CML LSCs through inhibiting NF-κB activity and reducing PD-L1 expression. Collectively, the combination of TKIs and IRAK1/4 inhibitors is an attractive strategy to achieve a radical cure of CML.

リンク情報
DOI
https://doi.org/10.1038/s41467-021-27928-8
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/35022428
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8755781
ID情報
  • DOI : 10.1038/s41467-021-27928-8
  • PubMed ID : 35022428
  • PubMed Central 記事ID : PMC8755781

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