Patient age at diagnosis is associated with the molecular characteristics of diffuse large B-cell lymphoma
Patient age at diagnosis is associated with the molecular characteristics of diffuse large B-cell lymphoma
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DOI：
10.1182/blood-2011-10-388470
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发表时间：
2012-02-23
期刊：
影响因子：
20.3
通讯作者：
Siebert, Reiner
中科院分区：
文献类型：
--
作者：
Klapper, Wolfram;Kreuz, Markus;Siebert, Reiner
弥漫性大B细胞淋巴瘤是成人患者中最常见的B细胞淋巴瘤类型，但也发生在儿童中。目前仅根据任意选择的年龄限制（例如，18岁或60岁）而非生物学合理限制将患者分配至治疗方案。共364弥漫性大B细胞淋巴瘤和相关的成熟侵袭性B细胞淋巴瘤以外的伯基特淋巴瘤从所有年龄组进行了全面的分子分析。先前报道的与弥漫性大B细胞淋巴瘤预后不良相关的几种生物学特征的概率，如ABC亚型、BCL 2表达或细胞遗传学复杂性，随着诊断时年龄的增加而增加。类似地，各种遗传特征，如IRF 4易位，1 q21，18 q21，7 p22和7 q21的增益，以及3q 27的变化，包括影响BCL 6基因座的增益和易位，与患者年龄显著相关，但年龄组之间没有截止值。如果年龄纳入多变量分析，遗传复杂性失去了其预后意义，而ABC亚型和年龄的预后影响是加性的。我们的数据表明，衰老是淋巴瘤生物学的主要决定因素。他们挑战了当前关于预后生物标志物和基于严格年龄界限的治疗分层的概念。（血。2012; 119（8）：1882-1887）
Diffuse large B-cell lymphoma is the most frequent type of B-cell lymphoma in adult patients but also occurs in children. Patients are currently assigned to therapy regimens based on arbitrarily chosen age limits only (eg, 18 or 60 years) and not biologically justified limits. A total of 364 diffuse large B-cell lymphomas and related mature aggressive B-cell lymphomas other than Burkitt lymphoma from all age groups were analyzed by comprehensive molecular profiling. The probability of several biologic features previously reported to be associated with poor prognosis in diffuse large B-cell lymphoma, such as ABC subtype, BCL2 expression, or cytogenetic complexity, increases with age at diagnosis. Similarly, various genetic features, such as IRF4 translocations, gains in 1q21, 18q21, 7p22, and 7q21, as well as changes in 3q27, including gains and translocations affecting the BCL6 locus, are significantly associated with patient age, but no cut-offs between age groups could be defined. If age was incorporated in multivariate analyses, genetic complexity lost its prognostic significance, whereas the prognostic impact of ABC subtype and age were additive. Our data indicate that aging is a major determinant of lymphoma biology. They challenge current concepts regarding both prognostic biomarkers and treatment stratification based on strict age cut-offs. (Blood. 2012; 119(8): 1882-1887)