文章：

在高风险慢性淋巴细胞白血病家族中的亲属中，IgM水平升高和游离轻链比值异常增加

Elevated IgM and abnormal free light chain ratio are increased in relatives from high-risk chronic lymphocytic leukemia pedigrees

原文发布日期：2019-02-26

DOI: 10.1038/s41408-019-0186-8

类型: Article

开放获取: 是

英文摘要：

Abnormal serum immunoglobulin (Ig) free light chains (FLC) are established biomarkers of early disease in multiple B-cell lymphoid malignancies, including chronic lymphocytic leukemia (CLL). Heavy chains have also been shown to be biomarkers in plasma cell disorders. An unanswered question is whether these Ig biomarkers are heritable, i.e., influenced by germline factors. CLL is heritable but highly heterogeneous. Heritable biomarkers could elucidate steps of disease pathogenesis that are affected by germline factors, and may help partition heterogeneity and identify genetic pleiotropies across malignancies. Relatives in CLL pedigrees present an opportunity to identify heritable biomarkers. We compared FLCs and heavy chains between relatives in 23 high-risk CLL pedigrees and population controls. Elevated IgM (eIgM) and abnormal FLC (aFLC) ratio was significantly increased in relatives, suggesting that these Ig biomarkers are heritable and could offer risk stratification in pedigree relatives. Within high-risk CLL pedigrees, B-cell lymphoid malignancies were five times more prevalent in close relatives of individuals with eIgM, prostate cancer was three times more prevalent in relatives of individuals with aFLC, and monoclonal B-cell lymphocytosis increased surrounding individuals with normal Ig levels. These different clustering patterns suggest Ig biomarkers have the potential to partition genetic heterogeneity in CLL and provide insight into distinct heritable pleiotropies associated with CLL.

摘要翻译： 

异常血清免疫球蛋白游离轻链已成为多种B细胞淋巴恶性肿瘤（包括慢性淋巴细胞白血病）早期疾病的生物标志物。重链也已被证明是浆细胞疾病的生物标志物。一个尚未解决的问题是这些免疫球蛋白生物标志物是否具有遗传性，即是否受种系因素影响。慢性淋巴细胞白血病具有遗传性但高度异质。可遗传的生物标志物能够阐明受种系因素影响的疾病发病机制环节，并有助于解析异质性、识别跨恶性肿瘤的遗传多效性。CLL谱系亲属为识别可遗传生物标志物提供了契机。我们比较了23个高危CLL家系亲属与人群对照组的轻链和重链水平。发现亲属中IgM升高和异常轻链比值显著增加，表明这些免疫球蛋白生物标志物具有遗传性，可为谱系亲属提供风险分层。在高危CLL家系中，IgM升高个体的近亲罹患B细胞淋巴恶性肿瘤的风险增加五倍，异常轻链比值个体的亲属患前列腺癌风险增加三倍，而免疫球蛋白水平正常者周围则出现单克隆B细胞淋巴细胞增多症。这些不同的聚集模式表明，免疫球蛋白生物标志物有望解析CLL的遗传异质性，并为理解与CLL相关的不同遗传多效性提供见解。

原文链接：

Elevated IgM and abnormal free light chain ratio are increased in relatives from high-risk chronic lymphocytic leukemia pedigrees