Phenotypic and genotypic characteristics of mastocytosis according to the age of onset.
Phenotypic and genotypic characteristics of mastocytosis according to the age of onset.
复制标题
DOI：
10.1371/journal.pone.0001906
复制
发表时间：
2008-04-09
期刊：
影响因子：
3.7
通讯作者：
Lortholary, Olivier
中科院分区：
文献类型：
--
作者：
Lanternier, Fanny;Cohen-Akenine, Annick;Palmerini, Fabienne;Feger, Frederic;Yang, Ying;Zermati, Yael;Barete, Stephane;Sans, Beatrix;Baude, Cedric;Ghez, David;Suarez, Felipe;Delarue, Richard;Casassus, Philippe;Bodemer, Christine;Catteau, Adeline;Soppelsa, Frederique;Hanssens, Katia;Arock, Michel;Sobol, Hagay;Fraitag, Sylvie;Canioni, Daniele;Moussy, Alain;Launay, Jean Marie;Dubreuil, Patrice;Hermine, Olivier;Lortholary, Olivier
成人肥大细胞增多症通常与持续的全身受累和c-kit 816突变有关，而儿科疾病大多局限于皮肤，通常会自行消退。我们前瞻性地纳入了 142 名经组织学证实患有肥大细胞增多症的成年患者。我们比较了在儿童时期开始患病的成年患者（第 1 组，n = 28）与在成年时开始患病的患者（第 2 组，n = 114）的表型和基因型特征。通过对 c-kit 外显子 17 和 8 至 13 进行测序，对皮肤活检进行基因型分析。根据 WHO 分类，两组的全身性疾病百分比相似（75% vs. 73%）。第 1 组和第 2 组的患者中分别有 42% 和 77% 的患者发现 C-kit 816 突变（p<0.001）。 816 c-kit 突变与第 2 组中的系统性肥大细胞增多症相关（87% 的患者患有系统性肥大细胞增多症，而 45% 的患者患有皮肤肥大细胞增多症，p = 0.0001）。在 5 岁之前出现肥大细胞增多症的患者中，有 23% 存在其他 c-kit 激活突变，在 6 岁至 15 岁之间为 0%，在成人时为 2%（p<0.001）。总之，肥大细胞增多症的发病机制根据发病年龄的不同而显着不同。在考虑 c-kit 靶向治疗时，我们的数据可能具有重要的治疗相关性。
Adult's mastocytosis is usually associated with persistent systemic involvement and c-kit 816 mutation, while pediatrics disease is mostly limited to the skin and often resolves spontaneously. We prospectively included 142 adult patients with histologically proven mastocytosis. We compared phenotypic and genotypic features of adults patients whose disease started during childhood (Group 1, n = 28) with those of patients whose disease started at adult's age (Group 2, n = 114). Genotypic analysis was performed on skin biopsy by sequencing of c-kit exons 17 and 8 to 13. According to WHO classification, the percentage of systemic disease was similar (75 vs. 73%) in 2 groups. C-kit 816 mutation was found in 42% and 77% of patients in groups 1 and 2, respectively (p<0.001). 816 c-kit mutation was associated with systemic mastocytosis in group 2 (87% of patients with systemic mastocytosis vs. 45% with cutaneous mastocytosis, p = 0.0001). Other c-kit activating mutations were found in 23% of patients with mastocytosis' onset before the age of 5, 0% between 6 and 15 years and 2% at adults' age (p<0.001). In conclusion, pathogenesis of mastocytosis significantly differs according to the age of disease's onset. Our data may have major therapeutic relevance when considering c-kit-targeted therapy.
登录
查看更多内容
影响因子：
1.5
作者：
AZANA, JM;TORRELO, A;ZAMBRANO, A
通讯作者：
ZAMBRANO, A
DOI：
10.1073/pnas.92.23.10560
发表时间：
1995-11-07
影响因子：
11.1
作者：
NAGATA, H;WOROBEC, AS;METCALFE, DD
通讯作者：
METCALFE, DD
影响因子：
4.1
作者：
Yanagihori, H;Oyama, N;Kaneko, F
通讯作者：
Kaneko, F
影响因子：
15.9
作者：
FURITSU, T;TSUJIMURA, T;KANAKURA, Y
通讯作者：
KANAKURA, Y
影响因子：
20.3
作者：
Escribano, L;Orfao, A;San Miguel, JF
通讯作者：
San Miguel, JF