# Feline Alimentary Lymphomas: Established Concepts and an Underexplored Molecular Landscape

**Authors:** Laura A. Szafron, Maciej Parys, Magdalena Parys, Lukasz M. Szafron

PMC · DOI: 10.3390/cimb48020218 · 2026-02-16

## TL;DR

This review highlights the lack of molecular research on feline alimentary lymphoma and its potential as a model for human cancer.

## Contribution

The paper emphasizes the underexplored molecular landscape of feline alimentary lymphoma and its translational potential for human oncology.

## Key findings

- Feline alimentary lymphoma is common but poorly characterized at the molecular level.
- There is a notable absence of high-throughput multi-omics studies in feline alimentary lymphoma.
- Feline alimentary lymphoma shares molecular similarities with human gastrointestinal T-cell lymphoma.

## Abstract

Domestic cats are among the most popular companion animals worldwide, with steadily increasing ownership and life expectancy. Paradoxically, despite their high prevalence and shared environmental exposures with humans, cats remain markedly underrepresented in molecular oncology research. Cancer is a leading cause of feline mortality, and alimentary lymphoma (AL) has emerged as one of the most common feline malignancies, yet its molecular landscape remains poorly characterized. This review summarizes current knowledge on feline AL, including epidemiology, risk factors, classification schemes, diagnostic challenges, treatment outcomes, and survival, with particular emphasis on low-grade alimentary lymphoma (LGAL), the most prevalent subtype. We discuss the complex relationship between chronic inflammatory enteropathies and lymphoma, highlighting diagnostic ambiguities and the inflammatory–neoplastic continuum. Importantly, we provide a critical overview of existing genomic, transcriptomic, epigenomic, proteomic, and metabolomic studies in feline AL, revealing a striking paucity of high-throughput, multi-omics analyses based on clinical material. Recent advances in feline genome assembly and annotation offer new opportunities to address these gaps. Furthermore, we compare feline AL with its human gastrointestinal T-cell lymphoma counterparts, demonstrating substantial molecular homology across key oncogenic pathways, including JAK/STAT signaling. This comparative perspective underscores the potential of feline AL as a naturally occurring model for the human disease. We conclude that comprehensive molecular characterization of feline AL is urgently needed to improve diagnostics, prognostication, and targeted therapies, with likely translational benefits for both veterinary and human oncology. Aim: The goal of this review is to summarize the current knowledge on feline alimentary lymphoma, including its origin, risk, classification, treatment approaches, and especially molecular landscape, which still remains poorly investigated with modern high-throughput techniques.

## Full-text entities

- **Genes:** IL-10 [NCBI Gene 493683], RIGI (RNA sensor RIG-I) [NCBI Gene 23586] {aka DDX58, RIG-I, RIG1, RLR-1, SGMRT2}, CDK9 (cyclin dependent kinase 9) [NCBI Gene 1025] {aka C-2k, CDC2L4, CTK1, PITALRE, TAK}, TP53 [NCBI Gene 493847], TRIM25 (tripartite motif containing 25) [NCBI Gene 7706] {aka EFP, RNF147, Z147, ZNF147}, STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774] {aka ADMIO, ADMIO1, APRF, HIES}, KCNB2 [NCBI Gene 101081116], CD79A (CD79a molecule) [NCBI Gene 973] {aka IGA, IGAlpha, MB-1, MB1}, CSMD3 [NCBI Gene 101092990], STAT5A (signal transducer and activator of transcription 5A) [NCBI Gene 6776] {aka MGF, STAT5}, TIA1 (TIA1 cytotoxic granule associated RNA binding protein) [NCBI Gene 7072] {aka ALS26, TIA-1, WDM}, NCAM1 (neural cell adhesion molecule 1) [NCBI Gene 4684] {aka CD56, MSK39, NCAM}, CR2 (complement C3d receptor 2) [NCBI Gene 1380] {aka C3DR, CD21, CR, CVID7, SLEB9}, FOXP3 (forkhead box P3) [NCBI Gene 50943] {aka AIID, DIETER, IPEX, JM2, PIDX, XPID}, IL-4 [NCBI Gene 751514], STAT5B (signal transducer and activator of transcription 5B) [NCBI Gene 6777] {aka GHISID2, STAT5}, NRAS (NRAS proto-oncogene, GTPase) [NCBI Gene 4893] {aka ALPS4, CMNS, N-ras, NCMS, NRAS1, NS6}, SAA [NCBI Gene 678660], NOTCH1 (notch receptor 1) [NCBI Gene 4851] {aka AOS5, AOVD1, TAN1, hN1}, IL-18 [NCBI Gene 493688], CDKN2A [NCBI Gene 101089220], THBS1 [NCBI Gene 101092689], TGF-beta [NCBI Gene 768263], IFN-gamma [NCBI Gene 493965], S100A12 [NCBI Gene 100526746], IL-2 [NCBI Gene 751114], BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596] {aka Bcl-2, PPP1R50}, CD79a [NCBI Gene 101083127], JAK3 [NCBI Gene 493680], TNFRSF8 (TNF receptor superfamily member 8) [NCBI Gene 943] {aka CD30, D1S166E, Ki-1}, ABL1 (ABL proto-oncogene 1, non-receptor tyrosine kinase) [NCBI Gene 25] {aka ABL, BCR-ABL, CHDSKM, JTK7, bcr/abl, c-ABL}, MDR1 [NCBI Gene 493707], TET2 [NCBI Gene 101092848], IL-5 [NCBI Gene 493803], COX2 [NCBI Gene 807936], JAK1 [NCBI Gene 101084377], CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, FSIP2 (fibrous sheath interacting protein 2) [NCBI Gene 401024] {aka SPGF34}, IL-6 [NCBI Gene 493687], SETD2 [NCBI Gene 101085029], ITGB2 (integrin subunit beta 2) [NCBI Gene 3689] {aka CD18, LAD, LCAMB, LFA-1, MAC-1, MF17}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, IFNA1 (interferon alpha 1) [NCBI Gene 3439] {aka IFL, IFN, IFN-ALPHA, IFN-alphaD, IFNA13, IFNA@}, GCSAM (germinal center associated signaling and motility) [NCBI Gene 257144] {aka GCAT2, GCET2, HGAL}, IGSF10 (immunoglobulin superfamily member 10) [NCBI Gene 285313] {aka CMF608}, CSMD2 [NCBI Gene 101084557], TNF-alpha [NCBI Gene 493755], IFNB1 (interferon beta 1) [NCBI Gene 3456] {aka IFB, IFF, IFN-beta, IFNB}, GNAI2 [NCBI Gene 101089679], GZMB (granzyme B) [NCBI Gene 3002] {aka C11, CCPI, CGL-1, CGL1, CSP-B, CSPB}, CD5 (CD5 molecule) [NCBI Gene 921] {aka LEU1, T1}
- **Diseases:** intestinal small-cell lymphomas (MESH:D015451), Enteropathy-associated T-cell lymphoma (MESH:D058527), CIE (MESH:D020277), injury to (MESH:D014947), bowel inflammation (MESH:D007249), T-cell anaplastic large-cell lymphoma (MESH:D017728), LGL (MESH:D054066), digestive neoplasm (MESH:D004067), Cancer (MESH:D009369), tubular carcinomas (MESH:D000230), PTCL-NOS (MESH:D016411), EATL I (MESH:D006969), GI-TLPD (MESH:D006470), squamous cell carcinoma (MESH:D002294), sarcoma (MESH:D012509), enteropathies (MESH:C538273), EATL II (MESH:C537730), death (MESH:D003643), ITCL-NOS (MESH:D016399), chronic infections (MESH:D000088562), immune-mediated disorders of the digestive tract (MESH:D004066), ALs (MESH:C536989), MALT (MESH:D018442), cytotoxic (MESH:D064420), EATL type II (MESH:D006938), gastrointestinal disease (MESH:D005767), LGAL (MESH:D008228), T-cell lymphoproliferative disorder of the gastrointestinal tract (MESH:D005770), B-cell gastrointestinal lymphoma (MESH:D016393), IBD (MESH:D015212), mammary cancer (MESH:D001943), LPE (MESH:D004751), thymic lymphoma (MESH:D013953), AL (MESH:D008223), CE (MESH:D002908), DLBCL (MESH:D016403)
- **Chemicals:** uridine (MESH:D014529), pinitol (MESH:C021730), venetoclax (MESH:C579720), Oncovin (MESH:D014750), chlorambucil (MESH:D002699), Omega-3 polyunsaturated fatty acids (MESH:D015525), arachidonate (MESH:D016718), gamma-glutamylglutamine (MESH:C047442), eicosapentaenoate (MESH:D015118), cyclophosphamide (MESH:D003520), hematoxylin (MESH:D006416), glucuronic acid (MESH:D020723), 2-hydroxyisobutyrate (MESH:C008039), polyunsaturated fatty acids (MESH:D005231), doxorubicin (MESH:D004317), 5-hydroxyindoleacetate (MESH:D006897), prednisolone (MESH:D011239), 2-oxindole-3-acetate (-), carbohydrates (MESH:D002241), phosphatidylcholine (MESH:D010713), lomustine (MESH:D008130), glutathione (MESH:D005978), 2-hydroxybutyrate (MESH:C031570), 3,4-dihydroxybenzoic acid (MESH:C009091), indole (MESH:C030374), tryptophan (MESH:D014364), sphingolipids (MESH:D013107)
- **Species:** Canis lupus familiaris (dog, subspecies) [taxon 9615], Nicotiana tabacum (American tobacco, species) [taxon 4097], Bacteroides sp. (species) [taxon 29523], Felis catus (cat, species) [taxon 9685], Homo sapiens (human, species) [taxon 9606], Fusobacterium (genus) [taxon 848], Enterobacteriaceae (enterobacteria, family) [taxon 543], Bacillota (clostridial firmicutes, phylum) [taxon 1239], Feline leukemia virus (no rank) [taxon 11768], Bacteroidia (class) [taxon 200643], gut metagenome (species) [taxon 749906], Feline immunodeficiency virus (no rank) [taxon 11673]
- **Mutations:** N642H, c.1924A > C, Q61K
- **Cell lines:** HEK293T — Homo sapiens (Human), Transformed cell line (CVCL_0063)

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12939859/full.md

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Source: https://tomesphere.com/paper/PMC12939859