虽然 T 细胞淋巴瘤被归类为成熟肿瘤，但新出现的证据表明恶性转化可能发生在 T 细胞成熟的早期阶段。在这项研究中，我们确定了多种 T 细胞淋巴瘤的克隆结构。我们的多维分析表明，这些淋巴瘤的很大一部分实际上是由未成熟的淋巴 T 细胞前体产生的，该前体处于 V(D)J 重排之前的成熟阶段，经历了分支进化。因此，在单细胞分辨率下，我们在选择性治疗压力下观察到相当多的克隆潮汐。 T 细胞受体下一代测序表明，TRBV20-1 基因片段的使用存在高度偏差，作为每位患者多个抗原受体重排的一部分。在分析的所有主要 T 细胞淋巴瘤亚型中均发现 TRBV20-1 占主导地位。这表明这个特定的 V 基因——独立于互补决定区 3 (CDR3) 的配置——可能代表恶性转化的驱动因素。总之，我们的数据表明，T 细胞淋巴瘤源自未成熟的淋巴前体细胞，并表现出相当大的瘤内异质性，这可能为这些难以治疗的癌症的复发和耐药提供基础。

While T cell lymphomas are classified as mature neoplasms, emerging evidence indicates that malignant transformation may occur at an earlier stage of T cell maturation. In this study, we determined clonal architectures in a broad range of T cell lymphomas. Our multidimensional profiling indicates that a large part of these lymphomas in fact emerge from an immature lymphoid T cell precursor at a maturation stage prior to V(D)J rearrangement that undergoes branching evolution. Consequently, at single cell resolution we observed considerable clonal tiding under selective therapeutic pressure. T cell receptor next-generation sequencing suggested a highly biased usage of TRBV20-1 gene segments as part of multiple antigen receptor rearrangements per patient. The predominance of TRBV20-1 was found across all major T cell lymphoma subtypes analyzed. This suggested that this particular V gene - independently of complementarity-determining region 3 (CDR3) configuration - may represent a driver of malignant transformation. Together, our data indicate that T cell lymphomas derive from immature lymphoid precursors and display considerable intratumoral heterogeneity that may provide the basis for relapse and resistance in these hard-to-treat cancers.