論文

国際誌
2022年5月5日

Lenalidomide promotes the development of TP53-mutated therapy-related myeloid neoplasms.

Blood
  • Adam S Sperling
  • Veronica Analia Guerra
  • James A Kennedy
  • Yuanqing Yan
  • Joanne I Hsu
  • Feng Wang
  • Andrew T Nguyen
  • Peter G Miller
  • Marie E McConkey
  • Vanessa A Quevedo Barrios
  • Ken Furudate
  • Linda Zhang
  • Rashmi Kanagal-Shamanna
  • Jianhua Zhang
  • Latasha D Little
  • Curtis E Gumbs
  • Naval G Daver
  • Courtney D DiNardo
  • Tapan M Kadia
  • Farhad Ravandi
  • Hagop M Kantarjian
  • Guillermo Garcia-Manero
  • Andrew Futreal
  • Benjamin L Ebert
  • Koichi Takahashi
  • 全て表示

140
16
開始ページ
1753
終了ページ
1763
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1182/blood.2021014956

There is a growing body of evidence that therapy-related myeloid neoplasms (t-MNs) with driver gene mutations arise in the background of clonal hematopoiesis (CH) under the positive selective pressure of chemo- and radiation therapies (CRT). Uncovering the exposure relationships that provide selective advantage to specific CH mutations is critical to understanding the pathogenesis and etiololgy of t-MNs. In a systematic analysis of 416 patients with t-MN and detailed prior exposure history, we found that TP53 mutations were significantly associated with prior treatment with thalidomide analogs, specifically lenalidomide. We demonstrated experimentally that lenalidomide treatment provides a selective advantage to Trp53-mutant hematopoietic stem and progenitor cells (HSPCs) in vitro and in vivo, the effect of which was specific to Trp53-mutant HSPCs and was not observed in HSPCs with other CH mutations. Due to differences in CK1a degradation, pomalidomide treatment did not provide an equivalent level of selective advantage to Trp53-mutant HSPCs providing a biological rationale for its use in patients at high risk for t-MN. These findings highlight the role of lenalidomide treatment in promoting TP53-mutated t-MNs and offer a potential alternative strategy to mitigate the risk of t-MN development.

リンク情報
DOI
https://doi.org/10.1182/blood.2021014956
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/35512188
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9837415
ID情報
  • DOI : 10.1182/blood.2021014956
  • PubMed ID : 35512188
  • PubMed Central 記事ID : PMC9837415

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