Emerging evidence indicates that thymocyte self-renewal induced by progenitor deprivation carries an oncogenic risk that is modulated by intra-thymic competition from differentiation-committed cells. Here we discuss formative studies demonstrating that, in mice, early thymocytes acquire self-renewing potential when thymic progenitor supply is sub-physiological and the importance of cellular competition with this at-risk cell population to prevent lymphoid malignancy. We also consider the possibility that increased thymic residency time, established under conditions of limited cellular competition, may have contributed to oncogenesis observed in early SCID-X1 trials when combined with insertional activation of proto-oncogenes such as LMO2.

中文翻译：

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免疫缺陷小鼠模型中胸腺细胞的自我更新和致癌风险：与针对造血干细胞群体的人类基因治疗临床试验相关吗？

越来越多的证据表明，祖细胞剥夺诱导的胸腺细胞自我更新具有致癌风险，该风险由分化分化细胞的胸腺内竞争调节。在这里，我们讨论形成性研究，这些研究表明，在小鼠中，当胸腺祖细胞供应低于生理状态时，早期胸腺细胞具有自我更新的潜能，并且细胞与这种高危细胞群竞争以预防淋巴恶性肿瘤非常重要。我们还考虑了在有限的细胞竞争条件下建立的胸腺驻留时间增加，可能与早期致癌基因（如LMO2）的插入激活相结合，可能有助于早期SCID-X1试验中观察到的肿瘤发生。