Carlotti Emanuela, Wrench David, Matthews Janet, Iqbal Sameena, Davies Andrew, Norton Andrew, Hart Jason, Lai Raymond, Montoto Silvia, Gribben John G, Lister T Andrew, Fitzgibbon Jude
Centre for Medical Oncology Laboratory, Barts and The London School of Medicine and Dentistry, London, United Kingdom.
Blood. 2009 Apr 9;113(15):3553-7. doi: 10.1182/blood-2008-08-174839. Epub 2009 Feb 6.
To investigate the cell of origin linking follicular (FL) and transformed (t-FL) lymphomas, we analyzed the somatic hypermutation (SHM) pattern of the variable region of the immunoglobulin heavy gene (IgH-VH) in 18 sequential FL/t-FL samples and a father (donor) and son (recipient), who developed FL and t-FL, after transplantation. Genealogic trees showed a pattern compatible with a common progenitor cell (CPC) origin in 13 cases. The identification of the t-FL clonotype in the previous FL sample and of the putative CPC sequence in both the FL/t-FL biopsies showed that the intraclonal diversity of FL and t-FL germinal centers (GCs) is more intricate than previously described, and all 3 clonotypes (CPC, FL, t-FL) may occur simultaneously within the same lymph node. On the basis of the father/son model, this CPC must be long-lived, providing a possible explanation for the incurable nature of this disease.
为了研究连接滤泡性淋巴瘤（FL）和转化性滤泡性淋巴瘤（t-FL）的起源细胞，我们分析了18例连续的FL/t-FL样本以及一位父亲（供体）和其儿子（受体）的免疫球蛋白重链基因可变区（IgH-VH）的体细胞高频突变（SHM）模式，该儿子在移植后分别发生了FL和t-FL。系谱树显示，13例病例呈现出与共同祖细胞（CPC）起源相符的模式。在前一个FL样本中鉴定出t-FL克隆型，并在FL/t-FL活检样本中鉴定出假定的CPC序列，这表明FL和t-FL生发中心（GCs）的克隆内多样性比之前描述的更为复杂，并且所有三种克隆型（CPC、FL、t-FL）可能在同一淋巴结内同时出现。基于父子模型，这种CPC必定寿命很长，这为该疾病难以治愈的特性提供了一种可能的解释。
