Blood:谁是朗格汉斯细胞组织细胞增生症驱动突变的携带者?

2020-08-11 MedSci原创 MedSci原创

朗格汉斯细胞组织细胞增生症(LCH)是一种由MAPK通路中的偶发性激活突变驱动的髓系肿瘤。本研究研究了CD34+c-Kit+FLT3+髓系祖细胞群在所有LCH病表现中作为潜在突变携带者的可能性。

朗格汉斯细胞组织细胞增生症(LCH)是一种由MAPK通路中的偶发性激活突变驱动的髓系肿瘤。

“误导的髓系树突状细胞(DC)”模型认为,高危、多系统、危险器官阳性(MS-RO+)LCH是由骨髓(BM)内驻留的多潜能造血祖细胞的驱动突变引起的,而低风险、MS-RO-和单系统(SS)LCH则是由循环或组织内驻留的树突状细胞(DC)的前体细胞的驱动突变引起的。

本研究研究了CD34+c-Kit+FLT3+髓系祖细胞群在所有LCH病表现中作为潜在突变携带者的可能性。

该群体包含单核细胞(Mo)/巨噬细胞(MF)、破骨细胞(OC)和树突状细胞(DC)寡能祖细胞。MS-RO+LCH患者骨髓来源的CD34+c-Kit+FLT3+细胞,在体外可产生郎格汉斯细胞(LC)样细胞。该祖细胞来源的LC样和DC后代都携带BRAF突变,证实了它们的共同起源。

在高危和低危LCH患者中,CD34+c-Kit+FLT3+祖细胞在血液中的百分比均高于健康献血者。在1例MS-RO+LCH患者中,CD34+c-Kit+FLT3+细胞在血液中的百分比及其BRAF突变后代均随化疗而改变。

在体外,高危和低危LCH患者外周血来源的CD34+c-Kit+FLT3+祖细胞均可产生DC和LC样细胞,但其驱动突变不易被检测到,可能是由于突变的祖细胞的百分比较低所导致的。此外,研究人员还在多个低危患者的病灶Mo/MF、DC、LC和/或OC样细胞以及血Mo和DC中发现突变的BRAF等位基因。

综上所述,研究人员推测,在高危和低危LCH患者中,驱动突变都存在于BM内驻留的髓系祖细胞中,该祖细胞可以动员到血液中。

原始出处:

Yanling Xiao,et al. Bone marrow-derived myeloid progenitors as driver mutation carriers in high- and low-risk Langerhans cell histiocytosis. Blood. August 4,2020.

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    2021-12-28 云舒

    xuexi

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    2021-06-18 qblt
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