作为I型干扰素（IFN）反应的重要调节因子，TMEM173参与免疫调节和细胞死亡诱导。最近的研究表明，激活TMEM173被认为是癌症免疫治疗的一种有前途的策略。然而，TMEM173在B细胞急性淋巴细胞白血病（B-ALL）中的转录组特征尚不清楚。采用定量实时聚合酶链式反应（qRT-PCR）和蛋白免疫印迹（WB）技术，确定了外周血单个核细胞（PBMCs）中TMEM173的mRNA和蛋白水平。采用Sanger测序评估了TMEM173的突变状态。进行单细胞RNA测序（scRNA-seq）分析，探索了不同类型的骨髓（BM）细胞中TMEM173的表达。B-ALL患者的PBMCs中TMEM173的mRNA和蛋白水平增加。此外，2名B-ALL患者的TMEM173序列中出现了移码突变。ScRNA-seq分析确定了高风险B-ALL患者BM中TMEM173的特定转录谱。具体来说，粒细胞、祖细胞、肥大细胞和类浆细胞树突状细胞（pDCs）中的TMEM173表达水平高于B细胞、T细胞、自然杀伤细胞（NK细胞）和树突状细胞（DCs）。子集分析进一步揭示了TMEM173和火山喷发效应因子气孔素D（GSDMD）在异相B（pre-B）细胞中受到限制，这些细胞在B-ALL进展过程中表达核因子kappa-B（NF-κB）、CD19和Bruton酪氨酸激酶（BTK）等增殖特征。此外，TMEM173与B-ALL中NK细胞和DCs的功能激活相关。我们的发现为高风险B-ALL患者BM中TMEM173的转录特征提供了见解。针对特定细胞中TMEM173的靶向激活可能为B-ALL患者提供新的治疗策略。© 2023年作者。

As an essential regulator of type I interferon (IFN) response, TMEM173 participates in immune regulation and cell death induction. In recent studies, activation of TMEM173 has been regarded as a promising strategy for cancer immunotherapy. However, transcriptomic features of TMEM173 in B-cell acute lymphoblastic leukemia (B-ALL) remain elusive.Quantitative real-time PCR (qRT-PCR) and western blotting (WB) were applied to determine the mRNA and protein levels of TMEM173 in peripheral blood mononuclear cells (PBMCs). TMEM173 mutation status was assessed by Sanger sequencing. Single-cell RNA sequencing (scRNA-seq) analysis was performed to explore the expression of TMEM173 in different types of bone marrow (BM) cells.The mRNA and protein levels of TMEM173 were increased in PBMCs from B-ALL patients. Besides, frameshift mutation was presented in TMEM173 sequences of 2 B-ALL patients. ScRNA-seq analysis identified the specific transcriptome profiles of TMEM173 in the BM of high-risk B-ALL patients. Specifically, expression levels of TMEM173 in granulocytes, progenitor cells, mast cells, and plasmacytoid dendritic cells (pDCs) were higher than that in B cells, T cells, natural killer (NK) cells, and dendritic cells (DCs). Subset analysis further revealed that TMEM173 and pyroptosis effector gasdermin D (GSDMD) restrained in precursor-B (pre-B) cells with proliferative features, which expressed nuclear factor kappa-B (NF-κB), CD19, and Bruton's tyrosine kinase (BTK) during the progression of B-ALL. In addition, TMEM173 was associated with the functional activation of NK cells and DCs in B-ALL.Our findings provide insights into the transcriptomic features of TMEM173 in the BM of high-risk B-ALL patients. Targeted activation of TMEM173 in specific cells might provide new therapeutic strategies for B-ALL patients.© 2023. The Author(s).