血管免疫母细胞型滤泡辅助 T 细胞淋巴瘤患者的克隆性造血和骨髓浸润。

IF 7.1 1区 医学 Q1 PATHOLOGY
Lennart Harland , Vanessa Borgmann , Franziska Otto , Mathis Overkamp , Irina Bonzheim , Falko Fend , Leticia Quintanilla-Martinez , Dominik Nann
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引用次数: 0

摘要

滤泡辅助T细胞(TFH)淋巴瘤存在RHOAG17V、IDH2R172、TET2和DNMT3A的复发性突变。TET2和DNMT3A突变是克隆性造血(CH)中最常受影响的基因。我们的研究旨在调查TFH/抗免疫母细胞性T细胞淋巴瘤(TFH-AITL)患者骨髓活检(BMB)中CH的频率及其与骨髓肿瘤的关联。研究人员使用定制面板通过新一代测序(NGS)分析了 22 名确诊为 TFH-AITL 患者的 29 个 BMB。从形态学上看,5 例 BMB 发现 TFH-AITL 浸润超过 5% 的 BM 细胞,其中 4 例经基于 NGS 的 T 细胞克隆证实。IDH2R172仅在1/29(3%)份样本中得到证实,RHOAG17V在2/29(7%)份样本中得到证实。在 24/29 例(83%)和 17/29 例(59%)BMB 中分别发现了 TET2 和 DNMT3A。在平行淋巴结(LN)中,突变频率分别为27%(IDH2R172)、64%(RHOAG17V)、86%(TET2)和50%(DNMT3A)。18/22(82%)例患者出现了与 LN 和 BMB 相同的 TET2 和/或 DNMT3A 突变,与 BM 浸润无关。3例患者的CH突变分别在TFH-AITL确诊前13、41和145个月被发现。TET2/DNMT3A突变且BM变异等位基因频率(VAF)>40%的病例(7/18,39%)血细胞计数较低。然而,只有血小板计数低具有统计学意义(P = 0.024)。在 4 个病例(4/22;18%)中发现了骨髓性肿瘤和/或 MDS 相关突变;所有病例的 TET2 VAF 都很高(>40%;p = 0.0114)。总之,82% 的 TFH-AITL 中存在 CH,且可在 TFH-AITL 诊断前 145 个月就被证实。NGS T 细胞克隆分析是确诊 TFH-AITL 骨髓浸润的绝佳工具。在 18% 的病例中发现了并发髓系肿瘤,且与等位基因负荷较高(>40%)的 TET2 突变有关。我们的研究表明,髓样肿瘤可能与 TFH 淋巴瘤同时发生或先于 TFH 淋巴瘤确诊。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Clonal Hematopoiesis and Bone Marrow Infiltration in Patients With Follicular Helper T-Cell Lymphoma of Angioimmunoblastic Type

Follicular helper T-cell (TFH) lymphoma harbors recurrent mutations of RHOAG17V, IDH2R172, TET2, and DNMT3A. TET2 and DNMT3A mutations are the most frequently affected genes in clonal hematopoiesis (CH). The aim of our study was to investigate the frequency of CH in bone marrow biopsies (BMB) of TFH/angioimmunoblastic T-cell lymphoma (TFH-AITL) patients and its association with myeloid neoplasms. A total of 29 BMB from 22 patients with a diagnosis of TFH–AITL were analyzed by next-generation sequencing (NGS) with a custom panel. Morphologically, 5 BMB revealed that TFH–AITL infiltrates of >5% of bone marrow (BM) cellularity confirmed in 4 cases by NGS-based T-cell clonality. IDH2R172 was demonstrated only in 1 (3%) of 29, and RHOAG17V in 2 (7%) of 29 samples. TET2 and DNMT3A were identified in 24 (83%) of 29 and 17 (59%) of 29 BMB, respectively. In the parallel lymph node the frequencies of mutations were 27% (IDH2R172), 64% (RHOAG17V), 86% (TET2), and 50% (DNMT3A). TET2 and/or DNMT3A mutations identical in lymph node and BMB were present in 18 (82%) of 22 patients, regardless of BM infiltration. In 3 cases the CH mutations were detected 13, 41, and 145 months before TFH–AITL diagnosis. Cases with TET2/DNMT3A mutations and BM variant allele frequencies >40% (7/18, 39%) showed lower blood counts. However, only low platelet count was statistically significant (P = .024). Myeloid neoplasms and/or myelodysplastic syndrome-related mutations were identified in 4 cases (4/22; 18%); all with high TET2 variant allele frequencies (>40%; P = .0114). In conclusion, CH is present in 82% of TFH–AITL and can be demonstrated up to 145 months before TFH–AITL diagnosis. NGS T-cell clonality analysis is an excellent tool to confirm TFH–AITL BM infiltration. Concurrent myeloid neoplasms were identified in 18% of the cases and were associated with TET2 mutations with high allelic burden (>40%). We demonstrated that myeloid neoplasms might occur simultaneously or precede the diagnosis of TFH lymphoma.

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来源期刊
Modern Pathology
Modern Pathology 医学-病理学
CiteScore
14.30
自引率
2.70%
发文量
174
审稿时长
18 days
期刊介绍: Modern Pathology, an international journal under the ownership of The United States & Canadian Academy of Pathology (USCAP), serves as an authoritative platform for publishing top-tier clinical and translational research studies in pathology. Original manuscripts are the primary focus of Modern Pathology, complemented by impactful editorials, reviews, and practice guidelines covering all facets of precision diagnostics in human pathology. The journal's scope includes advancements in molecular diagnostics and genomic classifications of diseases, breakthroughs in immune-oncology, computational science, applied bioinformatics, and digital pathology.
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