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Blood：重编程与骨髓增生异常综合征的克隆进化阶段

2019-04-23 qinqiyun MedSci原创

骨髓增生异常综合征重编程克隆进化
关注

髓样肿瘤，包括骨髓增生异常综合征(MDS)，是由造血干/祖细胞(HPCs）克隆获得体细胞突变所引起的一类遗传异质性疾病。前恶性突变的顺序及其对HPC自我更新和分化的影响尚不甚明确。Jasper Hsu等人发现MDS患者样本的重编程可从携带部分补充性突变的单个癌前细胞中诱导产生多能干细胞(iPSCs)，直接指示单个患者的突变时间顺序。重编程优先捕获突变较少的较少见的早期亚克隆。为评估克隆进化的功能性

髓样肿瘤，包括骨髓增生异常综合征(MDS)，是由造血干/祖细胞(HPCs）克隆获得体细胞突变所引起的一类遗传异质性疾病。前恶性突变的顺序及其对HPC自我更新和分化的影响尚不甚明确。

Jasper Hsu等人发现MDS患者样本的重编程可从携带部分补充性突变的单个癌前细胞中诱导产生多能干细胞(iPSCs)，直接指示单个患者的突变时间顺序。重编程优先捕获突变较少的较少见的早期亚克隆。

为评估克隆进化的功能性影响，研究人员将MDS-iPSCs诱导分化，发现在分化过程中最多发生4次连续的克隆异常，随着克隆变异，造血分化潜能逐渐降低。在疾病进展过程中。SF3B1与表观遗传突变协同作用，扰乱线粒体功能，导致受损线粒体积累，最终导致细胞凋亡和无效的红细胞生成。

重编程还揭示了复杂核型患者癌前突变的顺序，并将5q缺失（del[5q]）定义为早期细胞遗传异常。Del（5q）与TP53突变协同调节基因组的稳定性，促进染色体结构和核型异常的发生。重编程还可对白血病前克隆进化进行分子和功能性研究，明确了线粒体功能和基因组稳定性是MDS获得性体细胞突变所影响的关键通路。


原始出处：

Jasper Hsu， et al.Reprogramming identifies functionally distinct stages of clonal evolution in myelodysplastic syndromes. Blood 2019 ：blood.2018884338； doi： https：//doi.org/10.1182/blood.2018884338 

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    2020-01-04 huangshifeng

    #骨髓增生异常#

    0

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    2019-10-20 晓辰

    #克隆进化#

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    2019-07-30 fengyqf

    #骨髓增生#

    0

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    2020-03-31 aids221

    #克隆#

    0

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    2020-01-27 xinmeili

    #骨髓增生异常综合#

    0

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    2019-04-25 zhouqu_8

    #综合征#

    0

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    2019-04-23 orangesking

    好

    0

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