Arock M, Sotlar K, Akin C, Broesby-Olsen S, Hoermann G, Escribano L, Kristensen T K, Kluin-Nelemans H C, Hermine O, Dubreuil P, Sperr W R, Hartmann K, Gotlib J, Cross N C P, Haferlach T, Garcia-Montero A, Orfao A, Schwaab J, Triggiani M, Horny H-P, Metcalfe D D, Reiter A, Valent P
1] Molecular Oncology and Pharmacology, LBPA CNRS UMR8113, Ecole Normale Supérieure de Cachan, Cachan, France [2] Laboratory of Hematology, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
Institute of Pathology, Ludwig-Maximilians-University, Munich, Germany.
Leukemia. 2015 Jun;29(6):1223-32. doi: 10.1038/leu.2015.24. Epub 2015 Feb 4.
Although acquired mutations in KIT are commonly detected in various categories of mastocytosis, the methodologies applied to detect and quantify the mutant type and allele burden in various cells and tissues are poorly defined. We here propose a consensus on methodologies used to detect KIT mutations in patients with mastocytosis at diagnosis and during follow-up with sufficient precision and sensitivity in daily practice. In addition, we provide recommendations for sampling and storage of diagnostic material as well as a robust diagnostic algorithm. Using highly sensitive assays, KIT D816V can be detected in peripheral blood leukocytes from most patients with systemic mastocytosis (SM) that is a major step forward in screening and SM diagnosis. In addition, the KIT D816V allele burden can be followed quantitatively during the natural course or during therapy. Our recommendations should greatly facilitate diagnostic and follow-up investigations in SM in daily practice as well as in clinical trials. In addition, the new tools and algorithms proposed should lead to a more effective screen, early diagnosis of SM and help to avoid unnecessary referrals.
尽管在各类肥大细胞增多症中普遍检测到KIT基因的获得性突变，但用于检测和定量各种细胞及组织中突变类型和等位基因负担的方法尚无明确定义。我们在此就肥大细胞增多症患者诊断时及随访期间用于检测KIT突变的方法达成共识，以便在日常实践中具备足够的精度和灵敏度。此外，我们还提供了诊断材料的采样和储存建议以及一个可靠的诊断算法。使用高灵敏度检测方法，多数系统性肥大细胞增多症（SM）患者外周血白细胞中可检测到KIT D816V，这是筛查和SM诊断中的一大进步。此外，在疾病自然进程或治疗期间可对KIT D816V等位基因负担进行定量跟踪。我们的建议应能极大地促进日常实践及临床试验中SM的诊断和随访研究。此外，所提出的新工具和算法应能实现更有效的筛查、SM的早期诊断，并有助于避免不必要的转诊。
