T细胞急性淋巴细胞白血病（T-ALL）的发展与不同的驱动突变和/或染色体异常以及白血病细胞与免疫微环境之间的异常信号相互作用有关。为了更好地了解儿童T-ALL骨髓微环境和信号通路的变化，我们对来自单个中心的11名患者（10个诊断时点，5个诱导结束时点（EOI），1个复发时点）的骨髓进行了单细胞转录组分析。通过与健康骨髓细胞的比较，我们确定了T-ALL爆发细胞。T-ALL爆发相关的基因特征包括SOX4、STMN1、JUN、HES4、CDK6、ARMH1等最显著过表达的基因，其中一些与儿童T-ALL的不良预后有关。爆发细胞的转录组特征表现出显著的患者间异质性。诱导治疗后的免疫细胞表达谱显示出显著的变化。MRD+ EOI样本中的残存爆发细胞表现出PD-1和RhoGDI信号通路的显著上调（P < 0.01）。骨髓中T细胞和造血干细胞区的残存疾病存在细胞间的通信差异。总之，这些研究产生了关于儿童T-ALL骨髓景观的新见解，并扩展了我们对该疾病的认识。© 2023. 作者。

Different driver mutations and/or chromosomal aberrations and dysregulated signaling interactions between leukemia cells and the immune microenvironment have been implicated in the development of T-cell acute lymphoblastic leukemia (T-ALL). To better understand changes in the bone marrow microenvironment and signaling pathways in pediatric T-ALL, bone marrows collected at diagnosis (Dx) and end of induction therapy (EOI) from 11 patients at a single center were profiled by single cell transcriptomics (10 Dx, 5 paired EOI, 1 relapse). T-ALL blasts were identified by comparison with healthy bone marrow cells. T-ALL blast-associated gene signature included SOX4, STMN1, JUN, HES4, CDK6, ARMH1 among the most significantly overexpressed genes, some of which are associated with poor prognosis in children with T-ALL. Transcriptome profiles of the blast cells exhibited significant inter-patient heterogeneity. Post induction therapy expression profiles of the immune cells revealed significant changes. Residual blast cells in MRD+ EOI samples exhibited significant upregulation (P < 0.01) of PD-1 and RhoGDI signaling pathways. Differences in cellular communication were noted in the presence of residual disease in T cell and hematopoietic stem cell compartments in the bone marrow. Together, these studies generate new insights and expand our understanding of the bone marrow landscape in pediatric T-ALL.© 2023. The Author(s).