Institute of Hematology.
Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Blood Adv. 2021 Jun 22;5(12):2563-2568. doi: 10.1182/bloodadvances.2020003783.
TEMPI syndrome (telangiectasias, elevated erythropoietin level and erythrocytosis, monoclonal gammopathy, perinephric fluid collections, and intrapulmonary shunting) is a newly defined multisystemic disease with its pathophysiology largely unknown. Here, we report the whole-genome sequencing (WGS) analysis on the tumor-normal paired cells from a patient with TEMPI syndrome. WGS revealed somatic nonsynonymous single-nucleotide variants, including SLC7A8, NRP2, and AQP7. Complex structural variants of chromosome 2 were found, particularly within regions where some putative oncogenes reside. Of potential clinical relevance, duplication of 22q11.23 was identified, and the expression of the located gene macrophage migration inhibitory factor (MIF) was significantly upregulated in 3 patients with TEMPI syndrome. Importantly, the level of serum MIF in one patient with TEMPI syndrome was significantly decreased in accordance with the downtrend of plasma cells, M-protein, hemoglobin, and erythropoietin and the improvement of telangiectasias, perinephric fluid collections, and intrapulmonary shunting after treatment with plasma cell-directed therapy. In conclusion, our study provides insights into the genomic landscape and suggests a role of MIF in the pathophysiology of TEMPI syndrome.
TEMPI 综合征（毛细血管扩张、红细胞生成素水平升高和红细胞增多症、单克隆丙种球蛋白病、肾周液体积聚和肺内分流）是一种新定义的多系统疾病，其病理生理学在很大程度上尚不清楚。在这里，我们报告了一名 TEMPI 综合征患者的肿瘤-正常配对细胞的全基因组测序（WGS）分析。WGS 揭示了体细胞非同义单核苷酸变异，包括 SLC7A8、NRP2 和 AQP7。发现染色体 2 的复杂结构变异，特别是在一些推定的癌基因所在的区域。具有潜在临床相关性的是，22q11.23 的重复被鉴定出来，并且位于该位置的基因巨噬细胞移动抑制因子（MIF）的表达在 3 名 TEMPI 综合征患者中显著上调。重要的是，一名 TEMPI 综合征患者的血清 MIF 水平随着浆细胞、M 蛋白、血红蛋白和红细胞生成素的下降以及毛细血管扩张、肾周液体积聚和肺内分流的改善而在浆细胞定向治疗后显著降低。总之，我们的研究提供了对基因组景观的深入了解，并表明 MIF 在 TEMPI 综合征的病理生理学中起作用。
