We presume that defects in the NFAT pathway, reflected by the i/r -associated overexpression of CHN2/ b2-chimerin, downregulation of NFATC2 and dysregulation of several NFAT/NRON-related genes, may collectively lead to a downmodulation of the transcriptional activity of NFATC2. This ultimately results in a transcriptional dysregulation of NFATC2 targets, including genes controlling cell cycle, cell death and proliferation, and likely NFATC2 itself, and eventually to malignant proliferation of cd T-cells. In summary, our study provides further insight on the genetics and the pathogenic mechanisms of HSTL. We proved that HSTL cases harboring either a typical i or variant r are characterized by a constant loss. As RNAseq has not identified any disease-defining mutations and/or gene fusions, chromosome 7 imbalances remain the only driver genetic events found in this tumor. Based on the integrated genomic and transcriptomic data, we hypothesize that loss of 7p sequences is critical for the development of HSTL. This aberration associates with an Isoforskolin enhanced transcription of CHN2 and overexpression of b2-chimerin, what likely affects the NFATC2 related pathway and leads to a proliferative response. On the other hand, gain of 7q correlates with upregulation of several genes, including ABCB1, RUNDC3B and PPP1R9A, providing growth advantage to malignant cells and contributing to their intrinsic chemoresistance and aggressiveness. The latter process is probably also enhanced by genes activated by the frequently acquired trisomy 8, the set of dysregulated molecules previously discussed by Travert et al. and by an impaired immune synapse formation in neoplastic dcT-cells caused by an Benzyl alcohol overexpressed b2-chimerin and a downmodulated RAC1. The proposed here model of the pathogenesis of HSTL needs experimental validation. Further studies are also required to determine whether the mechanism underlying the i /r -driven pathogenesis of human HSTL are related to the id3-driven neoplastic transformation of murine cdT-cells. They are heavily infected by different vital viruses. Chinese sacbrood virus is the most stricken pathogen of Ac, which results in severe and deadly infections of the colony and eventually losses of the entire colony.