KIT mutation in mast cells and other bone marrow hematopoietic cell lineages in systemic mast cell disorders:: a prospective study of the Spanish Network on Mastocytosis (REMA) in a series of 113 patients
KIT mutation in mast cells and other bone marrow hematopoietic cell lineages in systemic mast cell disorders:: a prospective study of the Spanish Network on Mastocytosis (REMA) in a series of 113 patients
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DOI：
10.1182/blood-2006-04-015545
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发表时间：
2006-10-01
期刊：
影响因子：
20.3
通讯作者：
Orfao, Alberto
中科院分区：
文献类型：
--
作者：
Garcia-Montero, Andres C.;Jara-Acevedo, Maria;Orfao, Alberto
尽管c-kit/干细胞因子（SCF）信号通路在肥大细胞（MC）疾病中具有相关性，但在系统性肥大细胞增多症（SM）患者骨髓（BM）造血细胞的不同区室中，KIT突变的确切频率及其不同的诊断类别仍然未知。在这项研究中，我们前瞻性地分析了来自成年SM患者的BM MCs （n = 113）和其他BM细胞区室（n = 67）中荧光活化细胞分选（FACS）纯化群体中KIT突变的存在。我们的研究结果显示，除了高分化SM（29%）外，几乎所有患有惰性和侵袭性SM的成年人（93%）都存在D816V KIT突变，而其他KIT突变很少（< 3%）被检测到。在大约三分之一的MCs突变患者中，在CD34（+）造血细胞和嗜酸性粒细胞中也检测到KIT突变，在较小程度上，在单核细胞、中性粒细胞谱系BM前体细胞和淋巴细胞中也检测到KIT突变。大多数预后不良的SM患者（81%）在2个或更多BM骨髓细胞群中携带KIT突变，而在惰性病例中检测到的比例较小（27%）。这些结果将支持KIT突变是成人SM的标志的观点，它针对多能造血干细胞，并可能有助于解释先前在文献中观察到的差异。
Despite the relevance of the c-kit/stem cell factor (SCF) signaling pathway in mast cell (MC) diseases, the exact frequency of KIT mutations indifferent compartments of bone marrow (BM) hematopoietic cells of individuals with systemic mastocytosis (SM), and its different diagnostic categories, remains unknown. In this study, we prospectively analyzed the presence of KIT mutations in fluorescence-activated cell-sorting (FACS)-purified populations of BM MCs (n = 113) and other BM cell compartments (n = 67) from adults with SM. Our results show the presence of D816V KIT mutation in virtually all adults (93%) with indolent and aggressive forms of SM, except well-differentiated SM (29%), while other KIT mutations were rarely (< 3%) detected. In around one-third of patients with mutated MCs, the KIT mutation was also detected in CD34(+) hematopoietic cells and eosinophils, and, to a lesser extent, in monocytic, neutrophil-lineage BM precursor cells and lymphocytes. Most patient with poor-prognosis SM (81%) carried the KIT mutation in 2 or more BM myeloid cell populations, while this was detected in a smaller proportion (27%) of indolent cases. These results would support the notion that KIT mutation is a hallmark of adult SM where it targets a pluripotent hematopoietic stem cell, and may contribute to explaining previously observed discrepancies in the literature.