Jox A, Zander T, Kornacker M, Kanzler H, Küppers R, Diehl V, Wolf J
Department of Internal Medicine I, University of Cologne, Germany.
Ann Oncol. 1998 Mar;9(3):283-7. doi: 10.1023/a:1008249214328.
The malignant nature of Hodgkin-Reed Sternberg (H-RS) cells has been questioned due to their scarcity in lymphoma tissues. Recently, using micromanipulation of H-RS cells and single cell PCR evidence was obtained that H-RS cells represent a clonal B-cell population. In these studies H-RS cells were isolated from each one lymph node for a given case. In classical Hodgkin's disease (HD) it thus could not be ruled out that H-RS cell clonality reflected a locally restricted clonal proliferation. We analysed biopsy specimens from a patient suffering from HD for the presence of clonally related H-RS cells at primary diagnosis and during relapse of the disease.
In 1994 the H-RS cell line L1236 was generated from the peripheral blood of a patient suffering from a disseminating relapse of HD of mixed cellularity subtype. The patient had relapsed despite intensive treatment including high dose chemotherapy and autologous bone marrow transplantation. The clonal identity of this cell line with H-RS cells in situ was proven by amplifying identical Ig gene rearrangements of the cell line as well as of single H-RS cells picked from the patients bone marrow. Primers covering the CDR3 region were chosen from the H-RS cell specific VH1 gene rearrangement to detect H-RS cells of the identical clone by amplifying the rearranged VH1 genes in tissue samples obtained during disseminating relapsing disease and at primary diagnosis of HD in 1991.
The H-RS cell specific DNA sequence was detected in all affected tissues analysed including the cervical lymph node which has been exstirpated at primary diagnosis.
This finding indicates the existence of a clonal H-RS cell population during the first manifestation of HD and persistence and dissemination of this clone despite aggressive treatment. Thus, in the described case the malignant nature of H-RS cells defined by dissemination and recurrence of the identical H-RS cell clone in relapsing disease is proven.
霍奇金-里德-斯腾伯格（H-RS）细胞在淋巴瘤组织中数量稀少，其恶性本质一直受到质疑。最近，通过对H-RS细胞进行显微操作和单细胞PCR，获得了证据表明H-RS细胞代表一个克隆性B细胞群体。在这些研究中，从给定病例的每个淋巴结中分离出H-RS细胞。因此，在经典霍奇金淋巴瘤（HD）中，不能排除H-RS细胞克隆性反映局部受限的克隆增殖。我们分析了一名HD患者的活检标本，以检测疾病初诊时和复发时克隆相关的H-RS细胞。
1994年，从一名患有混合细胞型HD播散性复发患者的外周血中建立了H-RS细胞系L1236。尽管进行了包括高剂量化疗和自体骨髓移植在内的强化治疗，该患者仍复发。通过扩增该细胞系以及从患者骨髓中挑选的单个H-RS细胞的相同Ig基因重排，证明了该细胞系与原位H-RS细胞的克隆一致性。从H-RS细胞特异性VH1基因重排中选择覆盖互补决定区3（CDR3）区域的引物，通过扩增1991年HD播散性复发疾病期间和初诊时获得的组织样本中重排的VH1基因，检测相同克隆的H-RS细胞。
在所有分析的受累组织中均检测到H-RS细胞特异性DNA序列，包括初诊时切除的颈部淋巴结。
这一发现表明在HD首次出现时存在克隆性H-RS细胞群体，并且尽管进行了积极治疗，该克隆仍持续存在并播散。因此，在所描述的病例中，复发疾病中相同H-RS细胞克隆的播散和复发所定义的H-RS细胞的恶性本质得到了证实。
