Kadkol Shrihari S, Bland Joshua, Kavanaugh Ashley, Ni Hongyu, Nehru Vijeyaluxmi, Peace David
Department of Pathology, University of Illinois, Chicago, Chicago, IL, USA.
Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA.
Case Rep Hematol. 2021 Dec 28;2021:9740281. doi: 10.1155/2021/9740281. eCollection 2021.
B-cell lymphomas are neoplastic proliferations of clonal B lymphocytes. Clonality is generally determined by PCR amplification of VDJ rearrangements in the IgH heavy chain or VJ rearrangements in Ig/Ig light chain genes followed by capillary electrophoresis. More recently, next-generation sequencing (NGS) has been used to detect clonality in B-cell lymphomas because of the exponential amount of information that is obtained beyond just detecting a clonal population. The additional information obtained is useful for diagnostic confirmation, prognosis assessment, and response to therapy. In this study, we utilized NGS analysis to characterize two histologically distinct lymphomas (DLBCL and CLL/SLL) that were detected contemporaneously in an asymptomatic patient. NGS analysis showed that the same VDJ rearrangement was present in nodal (DLBCL) and marrow (CLL/SLL) biopsies confirming that the DLBCL resulted from Richter's transformation of a subclinical CLL/SLL. The V region of the rearrangement remained unmutated without somatic hypermutation. In silico analysis showed that the HCDR3 sequence was heterogeneous and not stereotypic. Minimal residual disease analysis by NGS showed that the tumor clone decreased by 2.84 logs in the bone marrow after R-CHOP therapy. However, a small number of tumor cells were still detected in the peripheral blood after R-CHOP therapy. Subsequent allogeneic transplantation was successful in eradicating the tumor clone and achieving deep molecular remission. We show that NGS analysis facilitated clinical management in our patient by helping to characterize the VDJ rearrangement in detail and by tracking minimal residual disease with high sensitivity and specificity.
B细胞淋巴瘤是克隆性B淋巴细胞的肿瘤性增殖。克隆性通常通过聚合酶链反应（PCR）扩增免疫球蛋白重链（IgH）中的VDJ重排或免疫球蛋白轻链基因中的VJ重排，随后进行毛细管电泳来确定。最近，由于下一代测序（NGS）除了能检测克隆群体外，还能获得大量信息，因此已被用于检测B细胞淋巴瘤的克隆性。所获得的额外信息有助于诊断确认、预后评估和治疗反应评估。在本研究中，我们利用NGS分析对一名无症状患者同时检测到的两种组织学不同的淋巴瘤（弥漫性大B细胞淋巴瘤[DLBCL]和慢性淋巴细胞白血病/小淋巴细胞淋巴瘤[CLL/SLL]）进行特征分析。NGS分析显示，在淋巴结（DLBCL）和骨髓（CLL/SLL）活检中存在相同的VDJ重排，证实DLBCL是由亚临床CLL/SLL的 Richter转化所致。重排的V区未发生体细胞超突变，仍保持未突变状态。计算机分析显示，互补决定区3（HCDR3）序列具有异质性，并非定型。NGS进行的微小残留病分析显示，R-CHOP治疗后骨髓中的肿瘤克隆减少了2.84个对数。然而，R-CHOP治疗后外周血中仍检测到少量肿瘤细胞。随后的异基因移植成功根除了肿瘤克隆并实现了深度分子缓解。我们表明，NGS分析通过帮助详细表征VDJ重排以及以高灵敏度和特异性追踪微小残留病，促进了我们患者的临床管理。
