Comparison of clonal architecture between primary and immunodeficient mouse-engrafted acute myeloid leukemia cells View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2022-03-25

AUTHORS

Naomi Kawashima, Yuichi Ishikawa, Jeong Hui Kim, Yoko Ushijima, Akimi Akashi, Yohei Yamaguchi, Hikaru Hattori, Marie Nakashima, Seara Ikeno, Rika Kihara, Takahiro Nishiyama, Takanobu Morishita, Koichi Watamoto, Yukiyasu Ozawa, Kunio Kitamura, Hitoshi Kiyoi

ABSTRACT

Patient-derived xenografts (PDX) are widely used as human cancer models. Previous studies demonstrated clonal discordance between PDX and primary cells. However, in acute myeloid leukemia (AML)-PDX models, the significance of the clonal dynamics occurring in PDX remains unclear. By evaluating changes in the variant allele frequencies (VAF) of somatic mutations in serial samples of paired primary AML and their PDX bone marrow cells, we identify the skewing engraftment of relapsed or refractory (R/R) AML clones in 57% of PDX models generated from multiclonal AML cells at diagnosis, even if R/R clones are minor at <5% of VAF in patients. The event-free survival rate of patients whose AML cells successfully engraft in PDX models is consistently lower than that of patients with engraftment failure. We herein demonstrate that primary AML cells including potentially chemotherapy-resistant clones dominantly engraft in AML-PDX models and they enrich pre-existing treatment-resistant subclones. More... »

PAGES

1624

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41467-022-29304-6

    DOI

    http://dx.doi.org/10.1038/s41467-022-29304-6

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1146558100

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/35338146


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