小柯机器人

英国威康桑格研究所Sam Behjati等研究人员合作揭示KMT2A重排的婴儿B细胞急性淋巴细胞白血病的独特发育状态。相关论文于2022年3月14日在线发表在《自然—医学》杂志上。

通过使用大量信使RNA（mRNA）元分析和检查单个淋巴细胞转录组与发育中的骨髓参照物，研究人员调查了KMT2A重排的婴儿B细胞急性淋巴细胞白血病（B-ALL）的发育状态。KMT2A排列的婴儿B-ALL独特地以早期淋巴细胞前体（ELP）状态为主，而较不利的NUTM1重排婴儿ALL表现出后期发育的B细胞信号，与大多数其他儿童B-ALL一致。研究人员将婴儿淋巴细胞与ELP细胞进行了比较，发现这种癌症具有混合骨髓-淋巴细胞的特征，包括非生理性的抗原组合，有可能成为实现癌症特异性的目标。研究人员通过流式细胞仪验证了经典组合的表面共表达。通过分析共同突变，研究人员确定KMT2A重排发生在非常早期的发育过程中，在造血分化之前，并强调了不能从转录状态推断出起源细胞。

据悉，KMT2A重排的婴儿白血病是一种侵袭性的儿童白血病，预后不佳。

附：英文原文

Title: Single-cell transcriptomics reveals a distinct developmental state of KMT2A-rearranged infant B-cell acute lymphoblastic leukemia

Author: Khabirova, Eleonora, Jardine, Laura, Coorens, Tim H. H., Webb, Simone, Treger, Taryn D., Engelbert, Justin, Porter, Tarryn, Prigmore, Elena, Collord, Grace, Piapi, Alice, Teichmann, Sarah A., Inglott, Sarah, Williams, Owen, Heidenreich, Olaf, Young, Matthew D., Straathof, Karin, Bomken, Simon, Bartram, Jack, Haniffa, Muzlifah, Behjati, Sam

Issue&Volume: 2022-03-14

Abstract: KMT2A-rearranged infant ALL is an aggressive childhood leukemia with poor prognosis. Here, we investigated the developmental state of KMT2A-rearranged infant B-cell acute lymphoblastic leukemia (B-ALL) using bulk messenger RNA (mRNA) meta-analysis and examination of single lymphoblast transcriptomes against a developing bone marrow reference. KMT2A-rearranged infant B-ALL was uniquely dominated by an early lymphocyte precursor (ELP) state, whereas less adverse NUTM1-rearranged infant ALL demonstrated signals of later developing B cells, in line with most other childhood B-ALLs. We compared infant lymphoblasts with ELP cells and revealed that the cancer harbored hybrid myeloid–lymphoid features, including nonphysiological antigen combinations potentially targetable to achieve cancer specificity. We validated surface coexpression of exemplar combinations by flow cytometry. Through analysis of shared mutations in separate leukemias from a child with infant KMT2A-rearranged B-ALL relapsing as AML, we established that KMT2A rearrangement occurred in very early development, before hematopoietic specification, emphasizing that cell of origin cannot be inferred from the transcriptional state. Single-cell transcriptomic and phylogenetic analyses reveal new insights into the developmental origin and potential therapeutic targets for a particularly aggressive form of B-cell acute lymphoblastic leukemia in infants.

DOI: 10.1038/s41591-022-01720-7

Source: https://www.nature.com/articles/s41591-022-01720-7

Nature Medicine：《自然—医学》，创刊于1995年。隶属于施普林格·自然出版集团，最新IF：87.241
官方网址：https://www.nature.com/nm/
投稿链接：https://mts-nmed.nature.com/cgi-bin/main.plex