Burkitt lymphoma (BL) is the most frequent B-cell lymphoma in pediatric patients. While most patients are cured, a fraction of them are resistant to therapy. To investigate BL heterogeneity and the features distinguishing therapy responders (R) from non-responders (NR), we analyzed by single-cell (sc)-transcriptomics diagnostic EBV-negative BL specimens. Analysis of the non-tumor component revealed a predominance of immune cells and a small representation of fibroblasts, enriched in NR. Tumors displayed patient-specific features, as well as shared subpopulations that expressed transcripts related to cell cycle, signaling pathways and cell-of-origin signatures. Several transcripts were differentially expressed in R versus NR. The top candidate, Tropomyosin 2 (TPM2), a member of the tropomyosin actin filament binding protein family, was confirmed to be significantly higher in NR both at the transcript and protein level. Stratification of patients based on TPM2 expression at diagnosis significantly correlated with prognosis, independently of TP53 mutations. These results indicate that BL displays transcriptional heterogeneity and identify candidate biomarkers of therapy resistance.

伯基特淋巴瘤 （BL） 是儿科患者中最常见的 B 细胞淋巴瘤。虽然大多数患者被治愈，但其中一小部分患者对治疗有抵抗力。为了研究 BL 异质性以及区分治疗反应者 （R） 和无反应者 （NR） 的特征，我们通过单细胞 （sc） 转录组学诊断 EBV 阴性 BL 标本进行了分析。非肿瘤成分的分析显示，免疫细胞占主导地位，成纤维细胞数量少，富含 NR。肿瘤显示出患者特异性特征，以及表达与细胞周期、信号通路和细胞来源特征相关的转录本的共享亚群。几个转录本在 R 与 NR 中差异表达。最佳候选者原肌球蛋白 2 （TPM2） 是原肌球蛋白肌动蛋白丝结合蛋白家族的成员，被证实在转录本和蛋白质水平上 NR 均显著升高。根据诊断时 TPM2 表达对患者进行分层与预后显著相关，与 TP53 突变无关。这些结果表明 BL 表现出转录异质性并识别治疗耐药的候选生物标志物。