Related Experiment Video

Updated: Feb 2, 2026

Murine Model of Leukemia Relapse to Induction Chemotherapy for Acute Lymphoblastic Leukemia
08:31

Murine Model of Leukemia Relapse to Induction Chemotherapy for Acute Lymphoblastic Leukemia

Published on: October 17, 2025

692

Targeting EIF4E signaling with ribavirin in infant acute lymphoblastic leukemia

Karen A Urtishak1,2, Li-San Wang3, Biljana Culjkovic-Kraljacic4

  • 1Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.

Oncogene
|November 28, 2018
PubMed

Insights

Elevated EIF4E protein in infant acute lymphoblastic leukemia (ALL) suggests targeting it with ribavirin. This repurposed drug inhibits EIF4E, reducing cancer cell growth and showing promise for treating infant ALL.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Infant acute lymphoblastic leukemia (ALL) has poor outcomes, necessitating novel therapeutic strategies.
  • EIF4E protein is frequently elevated in infant ALL, suggesting its potential as a therapeutic target.

Purpose of the Study:

  • To investigate EIF4E protein levels in infant ALL.
  • To evaluate the efficacy of ribavirin, an EIF4E inhibitor, as a potential treatment for infant ALL.

Main Methods:

  • Assessed EIF4E protein expression in infant ALL samples.
  • Treated infant ALL cells and cell lines (including KMT2A-rearranged and RS4:11) with ribavirin.
  • Utilized co-culture systems with bone marrow stromal cells (BMSCs) and xenograft mouse models.
  • Analyzed cell proliferation, protein expression, mRNA export, signaling pathways, and cell cycle progression.

Main Results:

  • Ribavirin significantly inhibited proliferation of actively dividing infant ALL cells in proportion to EIF4E expression.
  • Ribavirin treatment reduced levels of oncogenic EIF4E-regulated proteins (MYC, MCL1, NBN, BCL2, BIRC5) in KMT2A-R infant ALL and RS4:11 cells.
  • Ribavirin impaired EIF4E-dependent mRNA export and translation, induced S-phase cell cycle arrest, and caused EIF4E nuclear re-localization.
  • Ribavirin slowed peripheral blast increases in xenograft models and cooperated with L-asparaginase in reducing ALL cells.

Conclusions:

  • EIF4E is broadly elevated in infant ALL, validating it as a therapeutic target.
  • Ribavirin demonstrates preclinical activity by inhibiting EIF4E and reducing proliferation in KMT2A-R infant ALL.
  • Targeting EIF4E with ribavirin shows promise as a novel treatment strategy for infant ALL.

More Related Videos

In Ovo Xenografting of Patient-Derived Acute Lymphoblastic Leukemia (ALL) Cells (PDX-ALL)06:48

In Ovo Xenografting of Patient-Derived Acute Lymphoblastic Leukemia (ALL) Cells (PDX-ALL)

Published on: August 1, 2025

517
Isolation of the Side Population in Myc-induced T-cell Acute Lymphoblastic Leukemia in Zebrafish09:06

Isolation of the Side Population in Myc-induced T-cell Acute Lymphoblastic Leukemia in Zebrafish

Published on: May 4, 2017

7.0K

Related Concept Videos

What is Cell Signaling?02:03

What is Cell Signaling?

Despite the protective membrane that separates a cell from the environment, cells need the ability to detect and respond to environmental changes. Additionally, cells often need to communicate with one another. Unicellular and multicellular organisms use a variety of cell signaling mechanisms to communicate to respond to the environment.
130.4K
Endocrine Signaling01:45

Endocrine Signaling

Endocrine cells produce hormones to communicate with remote target cells found in other organs. The hormone reaches these distant areas using the circulatory system. This exposes the whole organism to the hormone but only those cells expressing hormone receptors or target cells are affected. Thus, endocrine signaling induces slow responses from its target cells but these effects also last longer.
68.1K
Paracrine Signaling01:21

Paracrine Signaling

Paracrine signaling allows cells to communicate with their immediate neighbors via secretion of signaling molecules. Such a signal can only trigger a response in nearby target cells because the signal molecules degrade quickly or are inactivated if not taken up. Prominent examples of paracrine signaling include nitric oxide signaling in blood vessels, synaptic signaling of neurons, the blood clotting system, tissue repair/wound healing, and local allergic skin reactions. Nitric oxide as a...
59.6K
Drug Dosing: Infants and Children01:29

Drug Dosing: Infants and Children

Pediatric patient dosages diverge from adults due to disparities in body surface area, total body water, and extracellular fluid per kilogram of body weight. The dosing regimen considers the variations in pharmacokinetics and pharmacology across distinct age groups, encompassing preterm newborns, infants, young children, older children, and adolescents. Calculation of pediatric patient doses is predicated on determining body surface area, which exhibits a superior correlation with the child's...
295
Bacterial Signaling01:30

Bacterial Signaling

Bacterial signaling can occur within bacteria (intracellular) or between bacteria (intercellular). At times, a group of bacteria behaves like a community. To achieve this, they engage in quorum sensing, the perception of higher cell density that causes changes in gene expression. Quorum sensing involves both extracellular and intracellular signaling. The signaling cascade starts with a molecule called an autoinducer (AI). Individual bacteria produce AIs that move out of the bacterial cell...
40.7K
Yeast Signaling01:28

Yeast Signaling

Yeasts are single-celled organisms, but unlike bacteria, they are eukaryotes (cells with a nucleus). Cell signaling in yeast is similar to signaling in other eukaryotic cells. A ligand, such as a protein or a small molecule released from a yeast cell, attaches to a receptor on the cell surface. The binding stimulates second-messenger kinases to activate or inactivate transcription factors that further regulate gene expression. Many of the yeast intracellular signaling cascades have similar...
17.3K