Oliver's mTOR Atlas Evidence Platform
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SLC15A3-mediated dipeptide metabolism confers antimetabolite resistance in lymphoma via mTORC1 activation.

Yang X, Zingaro VA, Boardman AP · 2026 · Journal of Clinical Investigation · Atlas ID YAN2026

What this study shows

SLC15A3-mediated dipeptide import sustains mTORC1 activation in B cell lymphomas, enabling resistance to antimetabolite chemotherapy; inhibiting SLC15A3 or mTORC1 restores drug sensitivity.

Abstract

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Antimetabolite chemotherapy resistance is a major barrier in B cell lymphoma. This study demonstrates that SLC15A3, a dipeptide transporter, mediates import of dipeptides that sustain mTORC1 activation in lymphoma cells, providing a metabolic route to antimetabolite resistance independent of de novo nucleotide synthesis. SLC15A3 inhibition resensitized resistant lymphoma cells to antimetabolite treatment.

Read the full abstract on PubMed →

At a glance

Evidence type A Animal model Marked A because it is an animal intervention or observation study measuring an organismal outcome (model: Lymphoma cell lines / mouse); the code names the system studied -- animal work can be rigorous and still not be human data.
Study type4 - Animal Study
Model systemLymphoma cell lines / mouse
JournalJournal of Clinical Investigation
Year2026
Peer reviewedYes
Record last updated2026-08-22
SourceDOI 10.1172/JCI199709 · PMID 42454485 · Free full text (PMC13367966)

Extracted findings

InterventionSLC15A3 inhibition; mTORC1 inhibition
TargetmTORC1; SLC15A3 dipeptide transporter; nutrient sensing
ModelMouse; human lymphoma cell lines
EffectSLC15A3 imports dipeptides to activate mTORC1, conferring antimetabolite chemoresistance; SLC15A3 or mTORC1 inhibition reverses resistance

In the Atlas

Related topics

SLC15A3mTORC1

Cite this paper

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Yang, X., Zingaro, V. A., & Boardman, A. P. (2026). SLC15A3-mediated dipeptide metabolism confers antimetabolite resistance in lymphoma via mTORC1 activation. Journal of Clinical Investigation. https://doi.org/10.1172/JCI199709

@article{YAN2026,
  author       = {Yang, X. and Zingaro, V. A. and Boardman, A. P.},
  title        = {{SLC15A3-mediated dipeptide metabolism confers antimetabolite resistance in lymphoma via mTORC1 activation}},
  journal      = {Journal of Clinical Investigation},
  year         = {2026},
  doi          = {10.1172/JCI199709},
  note         = {PMID: 42454485},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper. 

Barton, O. (2026). Oliver's mTOR Atlas (record YAN2026) [Data set]. https://mtor-atlas.org/study/YAN2026/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_YAN2026,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record YAN2026},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/YAN2026/},
  doi          = {10.5281/zenodo.22059963}
}