INSERM, UMR1287, Villejuif, France.
Gustave Roussy, Villejuif, France.
Br J Haematol. 2022 Jul;198(1):131-136. doi: 10.1111/bjh.18165. Epub 2022 Mar 30.
Myeloproliferative neoplasms (MPN) are mainly sporadic but inherited variants have been associated with higher risk development. Here, we identified an EPOR variant (EPOR ) in a large family diagnosed with JAK2 -positive polycythaemia vera (PV) or essential thrombocytosis (ET). We investigated its functional impact on JAK2 clonal amplification in patients and found that the variant allele fraction (VAF) was low in PV progenitors but increase strongly in mature cells. Moreover, we observed that EPOR alone induced a constitutive phosphorylation of STAT5 in cell lines or primary cells. Overall, this study points for searching inherited-risk alleles affecting the JAK2/STAT pathway in MPN.
骨髓增殖性肿瘤（MPN）主要为散发性，但已发现遗传性变异与更高的发病风险相关。在此，我们在一个被诊断为 JAK2 阳性真性红细胞增多症（PV）或原发性血小板增多症（ET）的大家族中发现了一个 EPOR 变异（EPOR ）。我们研究了它对患者 JAK2 克隆扩增的功能影响，发现变异等位基因分数（VAF）在 PV 祖细胞中较低，但在成熟细胞中强烈增加。此外，我们观察到 EPOR 单独诱导细胞系或原代细胞中 STAT5 的组成性磷酸化。总的来说，这项研究指出了在 MPN 中寻找影响 JAK2/STAT 通路的遗传风险等位基因。
