Transcriptomic validation of a 7,12 Dimethylbenz(a)anthracene (DMBA)-induced leukemia rat model: Parallels with human leukemogenesis.

BACKGROUND

Experimental animal models are essential for understanding the molecular mechanisms of human leukemia and testing potential therapies. Chemical induction using 7,12-dimethylbenz[a]anthracene (DMBA) has shown promise in recapitulating features of leukemogenesis in rodents, but its molecular fidelity to human disease remains underexplored. The aim of this study was to evaluate the transcriptomic landscape of a DMBA-induced leukemia rat model and assess its alignment with known gene expression signatures and oncogenic pathways in human leukemia.

METHODS

Male Wistar rats were treated with DMBA to induce leukemia. RNA was extracted from whole blood and subjected to RNA sequencing. Differentially expressed genes (DEG) were identified using RNA-seq by expectation-maximization and NOISeq. Functional enrichment analysis, Gene Ontology mapping, and protein interaction networks were analyzed via STRING. Prognostic relevance of key DEGs was explored using data from the Human Protein Atlas.

RESULTS

The DMBA-induced model showed significant upregulation of leukemia-associated genes, including FLT3, NRAS, KRAS, ABL1, BCR, and NPM1. The top 10 up- and downregulated genes were enriched in pathways related to cell fate, proliferation, apoptosis, and immune regulation. Particularly, genes such as MEIS2, CXCL9, and WIF1 were linked to hematopoietic dysregulation and poor prognosis in various cancers. Comparative analysis revealed strong transcriptomic overlap with human leukemia/carcinogenesis gene signatures, supporting the model's translational validity.

CONCLUSION

In conclusion, the DMBA-induced leukemia rat model exhibits a transcriptomic profile that closely mirrors key oncogenic and prognostic features of human leukemia. This model holds significant promise for preclinical studies targeting leukemogenesis and therapeutic intervention strategies.