弥漫大 B 细胞淋巴瘤 MYC 和 BCL2 畸变的多层次分析:利用靶向测序鉴定不同起源细胞的高风险患者亚群

IF 2.3 3区 医学 Q2 HEMATOLOGY
Gayaththri Vimalathas, Cecilie Steensboe Lang, Tina Marie Green, Michael Boe Møller, Charlotte Guldborg Nyvold, Marcus Høy Hansen, Thomas Stauffer Larsen
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引用次数: 0

摘要

导言:弥漫大B细胞淋巴瘤(DLBCL)在临床和生物学方面表现出显著的异质性。最近的研究在类似生殖中心B细胞(GCB)的DLBCL中发现了新的亚群,无论MYC和BCL2易位与否,这些亚群的预后都较差。我们根据多级畸变,尤其是MYC和BCL2的畸变,探讨了是否存在这样一个DLBCL高危亚群:对 111 例 DLBCL 患者的组织样本进行了 90 个基因的淋巴瘤面板测序,然后结合测序数据、免疫组化、荧光原位杂交和临床数据进行了综合分析:我们在DLBCL中发现了一个高危亚组,其定义为:免疫组化MYC和BCL2双重表达(DEL),MYC和BCL2同时易位(DHL-BCL2),MYC、CXCR4或两者突变,和/或BCL2扩增。高风险亚组占队列的41%,包括DHL-BCL2、DEL、可能代表最近描述的GCB亚组的GCB亚组以及非GCB患者亚组。在多变量分析中,高风险特征具有独立于年龄和IPI的预测价值。高危患者的5年总生存率为36%,而非高危患者的5年总生存率为76%:我们发现了一个独特的高危DLBCL亚组,其特征是MYC和BCL2畸变,超越了传统的DHL-BCL2和DEL,与原发细胞无关,从而扩大了预后不良的群体。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Multilevel Analysis of MYC and BCL2 Aberrations in Diffuse Large B-Cell Lymphoma: Identifying a High-Risk Patient Subgroup Across Cell-of-Origin Using Targeted Sequencing.

Introduction: Diffuse large B-cell lymphoma (DLBCL) exhibits striking clinical and biological heterogeneity. Recent studies have identified new subgroups within germinal center B-cell like (GCB) DLBCL, associated with inferior prognosis, irrespective of MYC and BCL2 translocations. We explored the existence of such a DLBCL high-risk subgroup, based on multilevel aberrations, especially focusing on MYC and BCL2.

Methods: Tissue samples from 111 DLBCL patients were sequenced with a 90-gene lymphoma panel, followed by integrative analyses combining sequencing data, immunohistochemistry, fluorescent in situ hybridization, and clinical data.

Results: We identified a high-risk subgroup in DLBCL defined by: dual immunohistochemical MYC and BCL2 expression (DEL), concurrent MYC and BCL2 translocations (DHL-BCL2), mutations in MYC, CXCR4, or both, and/or BCL2 amplification. The high-risk subgroup constituted 41% of the cohort and included DHL-BCL2, DEL, a GCB subgroup likely representing the recently described GCB subgroups, and a subset of non-GCB patients. In multivariate analysis, high-risk features provided independent predictive value from age and IPI. The 5-year overall survival was 36% in high-risk patients, compared to 76% in non-high-risk patients.

Conclusion: We identified a distinct high-risk DLBCL subgroup, characterized by MYC and BCL2 aberrations, beyond conventional DHL-BCL2 and DEL, and irrespective of cell-of-origin, thereby expanding the poor-prognosis group.

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来源期刊
CiteScore
5.50
自引率
0.00%
发文量
168
审稿时长
4-8 weeks
期刊介绍: European Journal of Haematology is an international journal for communication of basic and clinical research in haematology. The journal welcomes manuscripts on molecular, cellular and clinical research on diseases of the blood, vascular and lymphatic tissue, and on basic molecular and cellular research related to normal development and function of the blood, vascular and lymphatic tissue. The journal also welcomes reviews on clinical haematology and basic research, case reports, and clinical pictures.
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