Shi Zong-Yan, Sun Kai, Xie Dai-Hong, Wang Ya-Zhe, Jiang Hao, Jiang Qian, Huang Xiao-Jun, Qin Ya-Zhen
Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, No. 11 Xizhimen South Street, Xicheng District, Beijing 100044, People's Republic of China.
J Leukoc Biol. 2024 Dec 31;117(1). doi: 10.1093/jleuko/qiae191.
The prognostic significance of soluble immune checkpoint molecule TIM-3 and its ligands in the plasma has been illustrated in various solid tumors, but such study in newly diagnosed acute myeloid leukemia (AML) remains absent. Soluble TIM-3, Gal-9, and CEACAM1 levels in bone marrow plasma samples collected from 90 adult AML patients at diagnosis and 12 healthy donors were measured by enzyme-linked immunosorbent assays, and 16 AML patients were simultaneously tested cell membrane TIM-3 expression by multicolor flow cytometry. AML patients had significantly elevated soluble TIM-3 levels and similar soluble Gal-9 and CEACAM1 levels compared with healthy donors (P = 0.0003, 0.26, and 0.96, respectively). In the whole cohort, a high soluble TIM-3 level was the sole independent adverse prognostic factor for relapse-free survival (RFS) (P = 0.0060), and together with adverse European LeukemiaNet genetic risk they were independent poor prognostic factors for event-free survival (P = 0.0030 and 0.0040, respectively). A high soluble CEACAM1 level was significantly related to lower RFS (P = 0.028). In addition, a high soluble Gal-9 level had a significant association with lower RFS in patients receiving allogeneic hematopoietic stem cell transplantation at the first complete remission (P = 0.037). Furthermore, soluble TIM-3 level tended to have positive correlation with the percentage of nonblast myeloid TIM-3+ cells in nucleated cells in AML (r = 0.48, P = 0.073). Therefore, the high soluble TIM-3 level in the diagnostic BM plasma predicted poor outcome in adult AML patients, and a high sGal-9 level was associated with relapse after allogeneic hematopoietic stem cell transplantation.
可溶性免疫检查点分子TIM-3及其配体在血浆中的预后意义已在多种实体瘤中得到阐明，但在新诊断的急性髓系白血病（AML）中的此类研究仍然缺乏。通过酶联免疫吸附测定法测量了90例成年AML患者诊断时采集的骨髓血浆样本以及12名健康供体的可溶性TIM-3、Gal-9和CEACAM1水平，并通过多色流式细胞术同时检测了16例AML患者的细胞膜TIM-3表达。与健康供体相比，AML患者的可溶性TIM-3水平显著升高，而可溶性Gal-9和CEACAM1水平相似（P分别为0.0003、0.26和0.96）。在整个队列中，高可溶性TIM-3水平是无复发生存期（RFS）的唯一独立不良预后因素（P = 0.0060），并且与不良的欧洲白血病网遗传风险一起，它们是无事件生存期的独立不良预后因素（分别为P = 0.0030和0.0040）。高可溶性CEACAM1水平与较低的RFS显著相关（P = 0.028）。此外，高可溶性Gal-9水平与首次完全缓解时接受异基因造血干细胞移植的患者较低的RFS显著相关（P = 0.037）。此外，可溶性TIM-3水平倾向于与AML有核细胞中非原始髓系TIM-3+细胞的百分比呈正相关（r = 0.48，P = 0.073）。因此，诊断时骨髓血浆中高可溶性TIM-3水平预示成年AML患者预后不良，高sGal-9水平与异基因造血干细胞移植后的复发相关。
