加拿大迈克尔-史密斯基因组科学中心Marco A. Marra研究组的研究揭示了小儿急性髓细胞白血病（pAML）治疗反应的纵向单细胞图谱。这一研究成果于2023年11月16日发表在国际学术期刊《癌细胞》上。

研究人员使用单细胞RNA测序和单细胞ATAC测序对28例代表不同pAML亚型的患者在诊断、缓解和复发时的情况进行了分析。在诊断时，不同基因亚组的细胞组成各不相同。复发时，无论亚型如何，细胞层次结构都向更原始状态过渡。与诊断时的细胞相比，复发肿瘤中的原始细胞截然不同，髓系转录程序不足，而其他系谱程序则过高。

在一些患者中，还出现了类似于B淋巴细胞的层次结构。因此，该数据揭示了pAML治疗后出现明显亚型特异性可塑性的原因，并为潜在的靶向治疗策略提供了信息。

据了解，小儿急性髓性白血病具有细胞组成、驱动基因改变和预后异质性的特点。对于这种异质性特征及其如何影响儿科患者治疗反应的研究仍然不足。

附：英文原文

Title: A longitudinal single-cell atlas of treatment response in pediatric AML

Author: Sander Lambo, Diane L. Trinh, Rhonda E. Ries, Dan Jin, Audi Setiadi, Michelle Ng, Veronique G. Leblanc, Michael R. Loken, Lisa E. Brodersen, Fangyan Dai, Laura M. Pardo, Xiaotu Ma, Suzanne M. Vercauteren, Soheil Meshinchi, Marco A. Marra

Issue&Volume: 2023-11-16

Abstract: Pediatric acute myeloid leukemia (pAML) is characterized by heterogeneous cellular composition, driver alterations and prognosis. Characterization of this heterogeneity and how it affects treatment response remains understudied in pediatric patients. We used single-cell RNA sequencing and single-cell ATAC sequencing to profile 28 patients representing different pAML subtypes at diagnosis, remission and relapse. At diagnosis, cellular composition differed between genetic subgroups. Upon relapse, cellular hierarchies transitioned toward a more primitive state regardless of subtype. Primitive cells in the relapsed tumor were distinct compared to cells at diagnosis, with under-representation of myeloid transcriptional programs and over-representation of other lineage programs. In some patients, this was accompanied by the appearance of a B-lymphoid-like hierarchy. Our data thus reveal the emergence of apparent subtype-specific plasticity upon treatment and inform on potentially targetable processes.

DOI: 10.1016/j.ccell.2023.10.008

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(23)00364-1