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Updated: Jan 25, 2026

In Ovo Xenografting of Patient-Derived Acute Lymphoblastic Leukemia (ALL) Cells (PDX-ALL)
Published on: August 1, 2025
A genome-wide CRISPR/Cas9 screen reveals novel positive regulators of FTY720 sensitivity in acute lymphoblastic
Jaira Ferreira de Vasconcellos1, Leah Friedman2, Isha Satapathy2
1Department of Biology, James Madison University, 951 Carrier Drive, MSC 7801, 22807, Harrisonburg, VA, USA. vasconjf@jmu.edu.
Objective:
Acute lymphoblastic leukemia (ALL) is the most common form of childhood cancer. Fingolimod (FTY720) is a sphingosine-1-phosphate (S1P) receptor agonist that prevents lymphocytes from egressing from lymphoid tissues and has shown a cytotoxic effect on T-cell ALL (T-ALL) cells. However, the mechanism of action of FTY720 cytotoxicity in hematological malignancies is still unclear, and cell-specific effects have been reported. Here, we investigated the mechanism of cytotoxicity of FTY720 in T-ALL cells using a CRISPR-Cas9 genomic screening. Our goal was to identify novel positive regulators for the cytotoxic effect of FTY720 in T-ALL.
Results:
Cells treated with FTY720 were enriched for single-guide RNAs (sgRNAs) such as ZNF575, GPX3, FBXL15, DNAJB5, UBE2D1, ATXN7, C6orf201, RIC8A, RAB13, and C10orf12 when compared to the DMSO (vehicle control) samples. Altogether, our study identified novel genes that, when silenced, were positively correlated with the survival of T-ALL cells treated with FTY720.
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