Blood: The contribution of Vav1 mutations in the occurrence of mature T-cell tumors.

Activation mutations in the Vav ostrich nucleotide exchange factor 1 (Vav1) gene are reported in different subsypes of mature T-cell tumors (TCN).
, however, the carcinogenic activity associated with the Vav1 mutation in TCN remains unclear.
to analyze the role of Vav1 mutations in TCN disease, Fukumoto and others established a genetically modified mouse that expresses vav1 mutants cloned by human TCN.
Although the researchers did not observe tumors in these mice for up to a year, the tumors did develop in mice of comparable age with p53-/-Vav1-TG, and the incubation period of death in p53-/-Vav1-TG mice was shorter than in mice with p53-loss (p53-/-).
note that there were various mature TCNs in p53-/-Vav1-TG mice, while only immature TCNs appeared in P53-/-mice.
mature TCN in P53-/-Vav1-TG mice simulated exothymic blood T-cell lymphoma (PTCL)-GATA3, showing the characteristics of type 2 auxiliary T-cells (TH2).
the espase observed after transplanting p53-/-Vav1 or p53-/- tumor cells into naked mice suggests that these tumor cells have the ability to initiate tumors autonomously.
total transcription group analysis (WTA) showed that p53-/-Vav1-TG mice had multiple Myc-related path-riches in TCN compared to p53-/- or wild T-cells.
addition, the amplification of Myc bits in TCN in p53-/-Vav1-TG mice was cyclical.
, JQ1, a bromine domain inhibitor targeted by the Myc path, treated naked mice transplanted with p53-/-Vav1-TG tumor cells, extending the survival time of mice.
, the researchers believe that Vav1 mutations play a role in the malignant transformation of T-cells in the body, and that mice that express Vav1 mutations can provide an effective tool for screening new therapeutic targets with these mutations.
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