Fast, In Vivo Model for Drug-Response Prediction in Patients with B-Cell Precursor Acute Lymphoblastic Leukemia
Only half of patients with relapsed B-cell precursor (BCP) acute lymphoblastic leukemia (ALL) currently survive with standard treatment protocols. Predicting individual patient responses to defined drugs prior to application would help therapy stratification and could improve survival. With the purp...
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| Format: | Article |
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MDPI AG
2020-07-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/7/1883 |
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| author | Anton Gauert Nadine Olk Helia Pimentel-Gutiérrez Kathy Astrahantseff Lasse D. Jensen Yihai Cao Angelika Eggert Cornelia Eckert Anja I.H. Hagemann |
| author_facet | Anton Gauert Nadine Olk Helia Pimentel-Gutiérrez Kathy Astrahantseff Lasse D. Jensen Yihai Cao Angelika Eggert Cornelia Eckert Anja I.H. Hagemann |
| author_sort | Anton Gauert |
| collection | DOAJ |
| description | Only half of patients with relapsed B-cell precursor (BCP) acute lymphoblastic leukemia (ALL) currently survive with standard treatment protocols. Predicting individual patient responses to defined drugs prior to application would help therapy stratification and could improve survival. With the purpose to aid personalized targeted treatment approaches, we developed a human–zebrafish xenograft (ALL-ZeFiX) assay to predict drug response in a patient in 5 days. Leukemia blast cells were pericardially engrafted into transiently immunosuppressed <i>Danio rerio</i> embryos, and engrafted embryos treated for the test case, venetoclax, before single-cell dissolution for quantitative whole blast cell analysis. Bone marrow blasts from patients with newly diagnosed or relapsed BCP-ALL were successfully expanded in 60% of transplants in immunosuppressed zebrafish embryos. The response of BCP-ALL cell lines to venetoclax in ALL-ZeFiX assays mirrored responses in 2D cultures. Venetoclax produced varied responses in patient-derived BCP-ALL grafts, including two results mirroring treatment responses in two refractory BCP-ALL patients treated with venetoclax. Here we demonstrate proof-of-concept for our 5-day ALL-ZeFiX assay with primary patient blasts and the test case, venetoclax, which after expanded testing for further targeted drugs could support personalized treatment decisions within the clinical time window for decision-making. |
| first_indexed | 2024-03-10T18:31:06Z |
| format | Article |
| id | doaj.art-f7f95eb95934422ea756de925ffd04f0 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T18:31:06Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-f7f95eb95934422ea756de925ffd04f02023-11-20T06:39:39ZengMDPI AGCancers2072-66942020-07-01127188310.3390/cancers12071883Fast, In Vivo Model for Drug-Response Prediction in Patients with B-Cell Precursor Acute Lymphoblastic LeukemiaAnton Gauert0Nadine Olk1Helia Pimentel-Gutiérrez2Kathy Astrahantseff3Lasse D. Jensen4Yihai Cao5Angelika Eggert6Cornelia Eckert7Anja I.H. Hagemann8Department of Hematology/Oncology, Charité–Universitätsmedizin Berlin, 13353 Berlin, GermanyDepartment of Hematology/Oncology, Charité–Universitätsmedizin Berlin, 13353 Berlin, GermanyDepartment of Hematology/Oncology, Charité–Universitätsmedizin Berlin, 13353 Berlin, GermanyDepartment of Hematology/Oncology, Charité–Universitätsmedizin Berlin, 13353 Berlin, GermanyDepartment of Health, Medical and Caring Sciences, Linköping University, 58183 Linköping, SwedenDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 17165 Stockholm, SwedenDepartment of Hematology/Oncology, Charité–Universitätsmedizin Berlin, 13353 Berlin, GermanyDepartment of Hematology/Oncology, Charité–Universitätsmedizin Berlin, 13353 Berlin, GermanyDepartment of Hematology/Oncology, Charité–Universitätsmedizin Berlin, 13353 Berlin, GermanyOnly half of patients with relapsed B-cell precursor (BCP) acute lymphoblastic leukemia (ALL) currently survive with standard treatment protocols. Predicting individual patient responses to defined drugs prior to application would help therapy stratification and could improve survival. With the purpose to aid personalized targeted treatment approaches, we developed a human–zebrafish xenograft (ALL-ZeFiX) assay to predict drug response in a patient in 5 days. Leukemia blast cells were pericardially engrafted into transiently immunosuppressed <i>Danio rerio</i> embryos, and engrafted embryos treated for the test case, venetoclax, before single-cell dissolution for quantitative whole blast cell analysis. Bone marrow blasts from patients with newly diagnosed or relapsed BCP-ALL were successfully expanded in 60% of transplants in immunosuppressed zebrafish embryos. The response of BCP-ALL cell lines to venetoclax in ALL-ZeFiX assays mirrored responses in 2D cultures. Venetoclax produced varied responses in patient-derived BCP-ALL grafts, including two results mirroring treatment responses in two refractory BCP-ALL patients treated with venetoclax. Here we demonstrate proof-of-concept for our 5-day ALL-ZeFiX assay with primary patient blasts and the test case, venetoclax, which after expanded testing for further targeted drugs could support personalized treatment decisions within the clinical time window for decision-making.https://www.mdpi.com/2072-6694/12/7/1883pediatric cancerpersonalized therapyBCP-ALLzebrafishpatient-derived xenograft |
| spellingShingle | Anton Gauert Nadine Olk Helia Pimentel-Gutiérrez Kathy Astrahantseff Lasse D. Jensen Yihai Cao Angelika Eggert Cornelia Eckert Anja I.H. Hagemann Fast, In Vivo Model for Drug-Response Prediction in Patients with B-Cell Precursor Acute Lymphoblastic Leukemia Cancers pediatric cancer personalized therapy BCP-ALL zebrafish patient-derived xenograft |
| title | Fast, In Vivo Model for Drug-Response Prediction in Patients with B-Cell Precursor Acute Lymphoblastic Leukemia |
| title_full | Fast, In Vivo Model for Drug-Response Prediction in Patients with B-Cell Precursor Acute Lymphoblastic Leukemia |
| title_fullStr | Fast, In Vivo Model for Drug-Response Prediction in Patients with B-Cell Precursor Acute Lymphoblastic Leukemia |
| title_full_unstemmed | Fast, In Vivo Model for Drug-Response Prediction in Patients with B-Cell Precursor Acute Lymphoblastic Leukemia |
| title_short | Fast, In Vivo Model for Drug-Response Prediction in Patients with B-Cell Precursor Acute Lymphoblastic Leukemia |
| title_sort | fast in vivo model for drug response prediction in patients with b cell precursor acute lymphoblastic leukemia |
| topic | pediatric cancer personalized therapy BCP-ALL zebrafish patient-derived xenograft |
| url | https://www.mdpi.com/2072-6694/12/7/1883 |
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