Fast, In Vivo Model for Drug-Response Prediction in Patients with B-Cell Precursor Acute Lymphoblastic Leukemia

Cancers
Anton GauertAnja I H Hagemann

Abstract

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 Danio rerio 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 blast...Continue Reading

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Citations

Mar 7, 2021·Cancers·Wytske M van Weerden
Nov 10, 2021·Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine·Jakob Ernst Luis JordanIngolf Sack

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Methods Mentioned

BETA
biopsies
xenografts
xenografting
xenograft
antisense oligonucleotides
transgenic
biopsy
density gradient centrifugation
FCS
Flow Cytometric

Clinical Trials Mentioned

NCT03236857
NCT00114348
NCT01802814

Software Mentioned

Leica Application Suite X
FlowJo
Fiji

Related Concepts