首页    期刊浏览 2024年12月06日 星期五
登录注册

文章基本信息

  • 标题:Mechanical phenotyping reveals unique biomechanical responses in retinoic acid-resistant acute promyelocytic leukemia
  • 本地全文:下载
  • 作者:Brian Li ; Annie Maslan ; Sean E. Kitayama
  • 期刊名称:iScience
  • 印刷版ISSN:2589-0042
  • 出版年度:2022
  • 卷号:25
  • 期号:2
  • 页码:1-22
  • DOI:10.1016/j.isci.2022.103772
  • 语种:English
  • 出版社:Elsevier
  • 摘要:SummaryAll-trans retinoic acid (ATRA) is an essential therapy in the treatment of acute promyelocytic leukemia (APL), but nearly 20% of patients with APL are resistant to ATRA. As there are no biomarkers for ATRA resistance that yet exist, we investigated whether cell mechanics could be associated with this pathological phenotype. Using mechano-node-pore sensing, a single-cell mechanical phenotyping platform, and patient-derived APL cell lines, we discovered that ATRA-resistant APL cells are less mechanically pliable. By investigating how different subcellular components of APL cells contribute to whole-cell mechanical phenotype, we determined that nuclear mechanics strongly influence an APL cell’s mechanical response. Moreover, decondensing chromatin with trichostatin A is especially effective in softening ATRA-resistant APL cells. RNA-seq allowed us to compare the transcriptomic differences between ATRA-resistant and ATRA-responsive APL cells and highlighted gene expression changes that could be associated with mechanical changes. Overall, we have demonstrated the potential of “physical” biomarkers in identifying APL resistance.Graphical abstractDisplay OmittedHighlights•Mechanical phenotyping of acute promyelocytic leukemia (APL) cells•All-trans retinoic acid (ATRA) resistance in APL is associated with cell rigidity•RNA-seq of APL cells reveals genes that may potentially contribute to cell mechanicsCellular physiology; Molecular biology; Cell biology; Biomechanics
国家哲学社会科学文献中心版权所有