Induced lineage promiscuity undermines the efficiency of all-trans-retinoid-acid-induced differentiation of acute myeloid leukemia.
Induced lineage promiscuity undermines the efficiency of all-trans-retinoid-acid-induced differentiation of acute myeloid leukemia.
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诱导的谱系混杂破坏了全反式维A酸诱导的急性髓系白血病分化的效率
DOI：
10.1016/j.isci.2021.102410
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发表时间：
2021-05-21
期刊：
影响因子：
5.8
通讯作者：
Liu F
中科院分区：
文献类型：
--
作者：
Tang Y;Tian X;Xu Z;Cai J;Liu H;Liu N;Chen Z;Chen S;Liu F
全反式维甲酸（ATRA）可以诱导急性早幼粒细胞白血病（APL）（也称为急性髓系白血病（AML）的M3亚型）的终末分化。然而，非APL类型的AML对ATRA诱导的分化反应较差，并且细胞类型特异性抗ATRA的机制仍不清楚。在这里，我们使用单细胞转录组分析比较ATRA治疗期间两种AML细胞类型的分化轨迹。我们发现，在NB 4（APL/AML-M3）细胞中，ATRA激活典型的髓系因子，包括SPI 1，CEBPE和STAT 1，以指导向成熟粒细胞的近正常分化。相比之下，在HL 60（AML-M2）细胞中，ATRA诱导的分化是不完全的和混杂的，其特征在于骨髓和淋巴细胞生成基因表达程序的共诱导，以及与髓样分化相关的顺式调节元件的瞬时激活。我们的研究表明，ATRA在某些AML亚型中的分化诱导能力可能会受到治疗诱导的谱系混杂的影响。ATRA诱导两种AML细胞分化的单细胞分析在AML-M3/APL细胞中，ATRA诱导接近正常的粒细胞生成轨迹在AML-M2细胞中，ATRA诱导不完全分化和谱系混杂ATRA诱导的谱系混杂涉及瞬时顺式调节重编程癌症;转录组学
All-trans retinoid acid (ATRA) can induce terminal differentiation of acute promyelocytic leukemia (APL), also known as the M3 subtype of acute myeloid leukemia (AML). However, non-APL types of AML respond poorly to ATRA-induced differentiation, and the mechanism underlying cell-type-specific resistance against ATRA remains unclear. Here, we use single-cell transcriptome analysis to compare the differentiation trajectories of two AML cell types during ATRA treatment. We show that in NB4 (APL/AML-M3) cells, ATRA activates canonical myeloid lineage factors—including SPI1, CEBPE, and STAT1—to direct near-normal differentiation toward mature granulocytes. By contrast, in HL60 (AML-M2) cells, ATRA-induced differentiation is incomplete and promiscuous, which is characterized by coinduction of both myelopoiesis and lymphopoiesis gene expression programs, as well as transient activation of cis-regulatory elements associated with myeloid differentiation. Our study suggests that the differentiation inducing capacity of ATRA in certain subtypes of AML may be compromised by therapy-induced lineage promiscuity. Single-cell analysis of ATRA-induced differentiation in two AML cell types In AML-M3/APL cells, ATRA induces a near normal trajectory of granulopoiesis In AML-M2 cells, ATRA induces incomplete differentiation and lineage promiscuity ATRA-induced lineage promiscuity involves transient cis-regulatory reprogramming Cancer; Transcriptomics
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影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
DOI：
10.1073/pnas.75.5.2458
发表时间：
1978-01-01
影响因子：
11.1
作者：
COLLINS, SJ;RUSCETTI, FW;GALLO, RC
通讯作者：
GALLO, RC
DOI：
10.1073/pnas.0807297105
发表时间：
2008-09-30
影响因子：
11.1
作者：
Anderson, Ericka L.;Baltus, Andrew E.;Page, David C.
通讯作者：
Page, David C.
影响因子：
16
作者：
Heinz S;Benner C;Spann N;Bertolino E;Lin YC;Laslo P;Cheng JX;Murre C;Singh H;Glass CK
通讯作者：
Glass CK
DOI：
10.1073/pnas.1222863110
发表时间：
2013-02-26
影响因子：
11.1
作者：
Jiao, Bo;Ren, Zhi-Hong;Chen, Sai-Juan
通讯作者：
Chen, Sai-Juan