携带种系KIT K509I突变的家族性系统性肥大细胞增多症对伊马替尼、达沙替尼和PKC412治疗敏感。

Familial systemic mastocytosis with germline KIT K509I mutation is sensitive to treatment with imatinib, dasatinib and PKC412.

作者信息

de Melo Campos Paula, Machado-Neto João A, Scopim-Ribeiro Renata, Visconte Valeria, Tabarroki Ali, Duarte Adriana S S, Barra Flávia F C, Vassalo José, Rogers Heesun J, Lorand-Metze Irene, Tiu Ramon V, Costa Fernando F, Olalla Saad Sara T, Traina Fabiola

机构信息

Hematology and Hemotherapy Center, University of Campinas/Hemocentro - Unicamp, Instituto Nacional de Ciência e Tecnologia do Sangue, Campinas, São Paulo, Brazil.

Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.

出版信息

Leuk Res. 2014 Oct;38(10):1245-51. doi: 10.1016/j.leukres.2014.07.010. Epub 2014 Aug 1.

DOI:10.1016/j.leukres.2014.07.010

PMID:25139846

Abstract

Mastocytosis are myeloproliferative neoplasms commonly related to gain-of-function mutations involving the tyrosine kinase domain of KIT. We herein report a case of familial systemic mastocytosis with the rare KIT K509I germ line mutation affecting two family members: mother and daughter. In vitro treatment with imatinib, dasatinib and PKC412 reduced cell viability of primary mast cells harboring KIT K509I mutation. However, imatinib was more effective in inducing apoptosis of neoplastic mast cells. Both patients with familial systemic mastocytosis had remarkable hematological and skin improvement after three months of imatinib treatment, suggesting that it may be an effective front line therapy for patients harboring KIT K509I mutation.

摘要

肥大细胞增多症是一种髓系增殖性肿瘤，通常与涉及KIT酪氨酸激酶结构域的功能获得性突变有关。我们在此报告一例家族性系统性肥大细胞增多症，其罕见的KIT K509I种系突变影响了两名家庭成员：母亲和女儿。用伊马替尼、达沙替尼和PKC412进行体外治疗可降低携带KIT K509I突变的原代肥大细胞的细胞活力。然而，伊马替尼在诱导肿瘤性肥大细胞凋亡方面更有效。两名家族性系统性肥大细胞增多症患者在接受伊马替尼治疗三个月后血液学和皮肤状况均有显著改善，这表明它可能是携带KIT K509I突变患者的一种有效的一线治疗方法。