Analysis of CNS-ALL cell biology using PDX model and development of new therapeutic strategy

DOI
  • Kato Itaru
    Department of Pediatrics, Graduate School of Medicine, Kyoto University

Bibliographic Information

Other Title
  • PDXモデルによる中枢神経浸潤急性リンパ性白血病の解析と細胞療法の可能性

Description

<p>Central nervous system (CNS) involvement in acute lymphoblastic leukemia (ALL) has been considered as a feature of high-risk disease. Although this risk is mitigated by current intended CNS-directed treatments based on risk stratification strategies, currently 10% or more of children will die from relapsing or unresponsive ALL. CNS-directed treatments are effective; however, they do not specifically target CNS leukemic cells and are associated with both serious short-term toxicities and debilitating long-term morbidities. Understanding the biology of ALL cells that lodge in the CNS may lead to the development of drugs that specifically target them, and this could further improve outcomes with fewer complications. Using patient samples and patient-derived xenograft (PDX) models, we found that CNS-derived leukemic cells had transcriptional signatures indicative of physiological adaptation to hypoxic microenvironments, and VEGFA is one of the most up-regulated genes in CNS-derived leukemic cells. An in vivo preclinical assay showed that VEGFA could be targeted to treat patients with ALL and who have CNS involvement. We are now focusing on a therapeutic strategy against CNS leukemia using CART cells. These observations may be useful for not only further mechanistic research, but also future clinical trials.</p>

Journal

Related Projects

See more

Keywords

Details 詳細情報について

  • CRID
    1390285697589426560
  • NII Article ID
    130007896204
  • DOI
    10.11412/jspho.57.71
  • ISSN
    21895384
    2187011X
  • Text Lang
    ja
  • Article Type
    journal article
  • Data Source
    • JaLC
    • CiNii Articles
    • KAKEN
  • Abstract License Flag
    Disallowed

Report a problem

Back to top