Rapid in vivo Drug Response Prediction Using Leukemia Cell Grafts in Zebrafish Embryos

Area of Science:

• Oncology
• Developmental Biology
• Pharmacology

Background:

• Zebrafish xenotransplantation models are crucial for cancer research and personalized medicine.
• Existing methods require optimization for leukemia and rapid drug response assessment.

Purpose of the Study:

• To introduce ZefiX, a streamlined zebrafish xenotransplantation protocol for B-cell precursor acute lymphoblastic leukemia (BCP-ALL).
• To enable high-resolution, single-cell analysis of drug responses within clinical decision-making timelines.

Main Methods:

• Utilizing transient immunosuppression in zebrafish embryos via morpholino antisense oligonucleotides to enhance leukemia cell engraftment.
• Employing flow cytometry for precise, per-cell quantification of cell count, proliferation, and vitality post-treatment.
• Validating the protocol with targeted therapeutics like venetoclax and dasatinib, comparing results to clinical data and 2D cultures.

Main Results:

• The ZefiX protocol successfully engrafts and allows analysis of primary BCP-ALL samples and cell lines in zebrafish embryos.
• Flow cytometry provides detailed single-cell readouts of treatment efficacy.
• Drug responses in zebrafish xenografts correlate with clinical outcomes and outperform 2D culture models.
• The entire protocol is completed within 7 days.

Conclusions:

• ZefiX offers a rapid and effective platform for personalized drug screening in BCP-ALL and potentially other cancers.
• The protocol's speed and precision support timely clinical therapeutic strategies.
• Adaptability to solid tumors suggests broader applications in personalized oncology.