在一项日本实际研究中，分析了弥漫性大B细胞淋巴瘤（DLBCL）的分子亚型中具有暗区特征的分布和临床影响。
Distribution and clinical impact of molecular subtypes with Dark Zone signature of DLBCL in a Japanese real-world study.
发表日期：2023 Aug 08
作者：
Tomohiro Urata, Yusuke Naoi, Aixiang Jiang, Merrill Boyle, Kazutaka Sunami, Toshi Imai, Yuichiro Nawa, Yasushi Hiramatsu, Kazuhiko Yamamoto, Soichiro Fujii, Isao Yoshida, Tomofumi Yano, Ryota Chijimatsu, Hiroyuki Murakami, Kazuhiro Ikeuchi, Hiroki Kobayashi, Katsuma Tani, Hideki Ujiie, Hirofumi Inoue, Shuta Tomida, Akira Yamamoto, Takumi Kondo, Hideaki Fujiwara, Noboru Asada, Hisakazu Nishimori, Keiko Fujii, Nobuharu Fujii, Ken-Ichi Matsuoka, Keisuke Sawada, Shuji Momose, Jun-Ichi Tamaru, Asami Nishikori, Yasuharu Sato, Tadashi Yoshino, Yoshinobu Maeda, David W Scott, Daisuke Ennishi
来源：
Blood Advances
摘要：
细胞起源（COO）亚型对于弥漫性大B细胞淋巴瘤（DLBCL）在西方以外国家的分布和临床影响仍然未知。最近的文献还指出存在与生发中心暗区相关的额外COO亚型，需要广泛验证以推广其临床相关性。在本研究中，我们收集了一组未经治疗的日本DLBCL患者，并使用NanoString DLBCL90测定法确定了细胞起源亚型，包括暗区特征（DZsig）。为了比较分子亚型的分布和临床特征，我们使用了BC Cancer（BCC）组织的数据集（n = 804）。在本研究中，DLBCL90测定成功的1050名患者中，分别有35％、45％和6％的患者被识别为生发中心B细胞样（GCB）-DLBCL、活化B细胞样（ABC）-DLBCL和DZsig阳性（DZsigpos）-DLBCL，其中ABC-DLBCL的患病率显著地与BCC不同（P < 0.001）。 GCB-DLBCL、ABC-DLBCL和DZsigpos-DLBCL的2年总生存率分别为88％、75％和66％（P < 0.0001），DZsigpos-DLBCL患者的预后最差。相比之下，没有DZsig的GCB-DLBCL在使用利妥昔单抗联合免疫化疗后的预后良好。DZsigpos-DLBCL与CD10表达增加、MYC/BCL2表达同时存在和微环境成分消耗显著增加相关（所有P < 0.05）。这些结果证明了日本DLBCL中具有临床相关性的分子亚型的明显分布差异，并且DLBCL90测定作为COO的精确测定方法是一种在地理区域上具有一致性的强有力的预后指标。版权所有 © 2023年美国血液学会。
The distribution and clinical impact of cell-of-origin (COO) subtypes of diffuse large B-cell lymphoma (DLBCL) outside Western countries remain unknown. Recent literature also suggests that there is an additional COO subtype associated with the germinal center dark zone, that warrants wider validation to generalize clinical relevance. Here, we assembled a cohort of Japanese patients with untreated DLBCL and determined the refined COO subtypes, that include the dark zone signature (DZsig), using the NanoString DLBCL90 assay. To compare the distribution and clinical characteristics of the molecular subtypes, we used a dataset from the cohort of BC Cancer (BCC) (n = 804). Of the 1050 patients where DLBCL90 assay was successfully performed in our cohort, 35%, 45%, and 6% of patients were identified to be germinal center B-cell-like (GCB)-DLBCL, activated B-cell-like (ABC)-DLBCL, and DZsigpos-DLBCL, respectively, with the highest prevalence of ABC-DLBCL differing significantly from that of BCC (P < 0.001). GCB-DLBCL, ABC-DLBCL, and DZsigpos-DLBCL were associated with two-year overall survival rates of 88%, 75%, and 66%, respectively (P < 0.0001), with patients of the DZsigpos-DLBCL having the poorest prognosis. In contrast, GCB-DLBCL without DZsig showed excellent outcomes following rituximab-containing immunochemotherapy. DZsigpos-DLBCL was associated with the significant enrichment of tumors with CD10 expression, concurrent MYC/BCL2 expression, and depletion of microenvironmental components (all P < 0.05). These results provide evidence of the distinct distribution of clinically relevant molecular subtypes in Japanese DLBCL and that refined COO, as measured by the DLBCL90 assay, is a robust prognostic biomarker that is consistent across geographical areas.Copyright © 2023 American Society of Hematology.