Elucidating minimal residual disease of paediatric B-cell acute lymphoblastic leukaemia by single-cell analysis
Elucidating minimal residual disease of paediatric B-cell acute lymphoblastic leukaemia by single-cell analysis
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通过单细胞分析阐明儿童 B 细胞急性淋巴细胞白血病的微小残留病
DOI：
10.1038/s41556-021-00814-7
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发表时间：
2022-02
影响因子：
21.3
通讯作者：
Xiaofa
中科院分区：
文献类型：
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作者：
Yingchi Zhang;Shicheng Wang;Jingliao Zhang;Chao Liu;Xinqi Li;Wenbo Guo;Yongjuan Duan;Xiaoyan Chen;Suyu Zong;Jiarui Zheng;Yixuan Wu;Xiaoli Chen;Xuelian Cheng;Yanxia Chang;Yue Wang;Feng Ding;Wenyu Yang;Xiaojuan Chen;Ye Guo;Li Zhang;Yumei Chen;Yao Zou;Xiaofa
化疗后残留的微小病变是血液系统恶性肿瘤和实体癌最有价值的预后标志。不幸的是，由于残留细胞的稀有和异质性，我们对微小残留病引起的耐药性的了解是有限的。在这里，我们产生了161,986个单细胞转录本，结合单细胞RNA测序和B细胞受体测序，分析了B细胞急性淋巴细胞白血病(B-ALL)在诊断、残留和复发时的动态变化。与初诊时相比，复发时的白血病细胞倾向于向低分化状态转变，而残留细胞的变化则更为复杂。差异分析强调了残留细胞、抗性克隆和带有MLL重排的B-ALL中缺氧通路的激活。体外和体内模型均表明，抑制低氧途径可使白血病细胞对化疗敏感。这种对微小残留疾病的单细胞分析为确定B-ALL的有效治疗机会开辟了一条途径。
Minimal residual disease that persists after chemotherapy is the most valuable prognostic marker for haematological malignancies and solid cancers. Unfortunately, our understanding of the resistance elicited in minimal residual disease is limited due to the rarity and heterogeneity of the residual cells. Here we generated 161,986 single-cell transcriptomes to analyse the dynamic changes of B-cell acute lymphoblastic leukaemia (B-ALL) at diagnosis, residual and relapse by combining single-cell RNA sequencing and B-cell-receptor sequencing. In contrast to those at diagnosis, the leukaemic cells at relapse tended to shift to poorly differentiated states, whereas the changes in the residual cells were more complicated. Differential analyses highlighted the activation of the hypoxia pathway in residual cells, resistant clones and B-ALL with MLL rearrangement. Both in vitro and in vivo models demonstrated that inhibition of the hypoxia pathway sensitized leukaemic cells to chemotherapy. This single-cell analysis of minimal residual disease opens up an avenue for the identification of potent treatment opportunities for B-ALL.
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影响因子：
5.8
作者：
Liberzon, Arthur;Subramanian, Aravind;Mesirov, Jill P.
通讯作者：
Mesirov, Jill P.
来自1,092个人基因组的遗传变异的综合图。
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
50.3
作者：
Roberts KG;Morin RD;Zhang J;Hirst M;Zhao Y;Su X;Chen SC;Payne-Turner D;Churchman ML;Harvey RC;Chen X;Kasap C;Yan C;Becksfort J;Finney RP;Teachey DT;Maude SL;Tse K;Moore R;Jones S;Mungall K;Birol I;Edmonson MN;Hu Y;Buetow KE;Chen IM;Carroll WL;Wei L;Ma J;Kleppe M;Levine RL;Garcia-Manero G;Larsen E;Shah NP;Devidas M;Reaman G;Smith M;Paugh SW;Evans WE;Grupp SA;Jeha S;Pui CH;Gerhard DS;Downing JR;Willman CL;Loh M;Hunger SP;Marra MA;Mullighan CG
通讯作者：
Mullighan CG
Rictor 是骨髓早期 B 细胞发育所必需的
影响因子：
3.7
作者：
Zhang Y;Hu T;Hua C;Gu J;Zhang L;Hao S;Liang H;Wang X;Wang W;Xu J;Liu H;Liu B;Cheng T;Yuan W
通讯作者：
Yuan W
影响因子：
64.5
作者：
Malta TM;Sokolov A;Gentles AJ;Burzykowski T;Poisson L;Weinstein JN;Kamińska B;Huelsken J;Omberg L;Gevaert O;Colaprico A;Czerwińska P;Mazurek S;Mishra L;Heyn H;Krasnitz A;Godwin AK;Lazar AJ;Cancer Genome Atlas Research Network;Stuart JM;Hoadley KA;Laird PW;Noushmehr H;Wiznerowicz M
通讯作者：
Wiznerowicz M