A genome-wide CRISPR/Cas9 screen reveals novel positive regulators of FTY720 sensitivity in acute lymphoblastic leukemia cells

  • BMC Res Notes. 2026 Jan 23;19(1):75. doi: 10.1186/s13104-026-07654-4.
Jaira Ferreira de Vasconcellos  1 ,  Leah Friedman  2 ,  Isha Satapathy  2 ,  Nicole Cubbage  2 ,  Jasmin Palmer  2 ,  Saurav Majumder  3 ,  Mari Kono  3
Affiliations
  • 1. Department of Biology, James Madison University, 951 Carrier Drive, MSC 7801, 22807, Harrisonburg, VA, USA. [email protected].
  • 2. Department of Biology, James Madison University, 951 Carrier Drive, MSC 7801, 22807, Harrisonburg, VA, USA.
  • 3. Genetics and Biochemistry Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 10 Center Dr, MD, 20892, Bethesda, USA.
PMID: 41578398 DOI: 10.1186/s13104-026-07654-4
Abstract

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.

Keywords
ALL; Acute lymphoblastic leukemia; CRISPR/Cas9 screen; FTY720.
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