肥大细胞增多症患者中 KIT M541L 变异的患病率和影响。

Q2 Medicine Oncotarget Pub Date : 2024-07-22 DOI:10.18632/oncotarget.28614
Luisa N Dominguez Aldama, Eric Karlins, Xiaoping Sun, Daniel Veltri, Hirsh D Komarow, Irina Maric, Dean D Metcalfe, Melody C Carter
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引用次数: 0

摘要

KIT 的激活突变(尤其是 D816V)与肥大细胞增多症有关。此外,杂合子 KIT M541L 的表达主要见于小儿肥大细胞增多症患者。因此,我们与祖先匹配的 1000 基因组对照组(500 人)和特发性过敏性休克患者(23 人)相比,研究了这种变异在儿童和成人肥大细胞增多症患者(100 人)中的患病率。然后,我们比较了全身性和皮肤性肥大细胞增多症患者的临床症状和实验室数据,以及具有和不具有 KIT M541L 变异的匹配队列的骨髓组织病理学。总体而言,在 19 人中发现了 KIT M541L 变异体;大多数人被诊断为伴有 KIT D816V 突变的全身性肥大细胞增多症(89.4%)。各组间的外周血参数无明显差异。携带 KIT M541L 变异的肥大细胞增多症患者的症状与无 KIT M541L 变异的匹配参照组群(n = 13/81)相比无明显差异。在特发性过敏性休克患者中,没有观察到明显的关联。这项研究独特地研究了 KIT M541L 变体在成人和儿童肥大细胞增多症患者中的患病率和影响,并根据疾病变体进行了进一步分层。据我们所知,这是第一项显示 KIT M541L 位点与肥大细胞增多症存在显著遗传关联的病例/对照研究。
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Prevalence and impact of the KIT M541L variant in patients with mastocytosis.

Activating mutations in KIT, particularly D816V, have been associated with mastocytosis. Additionally, expression of heterozygous KIT M541L has been primarily reported in patients with pediatric mastocytosis. We thus examined the prevalence of this variant in pediatric and adult patients with mastocytosis (n = 100) compared to ancestry-matched 1000 genomes controls (n = 500) and patients with idiopathic anaphylaxis (n = 23). We then compared clinical symptoms and laboratory data on patients with systemic and cutaneous mastocytosis and bone marrow histopathology on a matched cohort with and without the KIT M541L variant. Overall, the KIT M541L variant was identified in 19 individuals; the majority were diagnosed with systemic mastocytosis (89.4%) with an associated KIT D816V mutation. There were no significant differences in peripheral blood parameters between groups. Patients with mastocytosis carrying the KIT M541L variant did not demonstrate significant differences in symptomatology compared to a matched reference cohort (n = 13/81) without KIT M541L. In patients with idiopathic anaphylaxis, no significant associations were observed. This study uniquely examines the prevalence and impact of the KIT M541L variant in both adult and pediatric patients with mastocytosis further stratified by disease variant. To our knowledge, this is the first case/control study to show a significant genetic association with mastocytosis at the KIT M541L locus.

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来源期刊
Oncotarget
Oncotarget Oncogenes-CELL BIOLOGY
CiteScore
6.60
自引率
0.00%
发文量
129
审稿时长
1.5 months
期刊介绍: Information not localized
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