Li Yuxi, Cui Rui, Yu Ying, Huang Yanshan, Yan Yuting, Sun Jingwen, Yuan Jingjing, Wang Tingyu, Lyu Rui, Xiong Wenjie, Wang Qi, Liu Wei, An Gang, Sui Weiwei, Xu Yan, Huang Wenyang, Wang Liang, Zou Dehui, Zhang Fengkui, Wang Huijun, Qiu Lugui, Yi Shuhua
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, People's Republic of China.
Tianjin Institutes of Health Science, Tianjin, 301600, People's Republic of China.
Oncologist. 2025 Mar 10;30(3). doi: 10.1093/oncolo/oyae350.
NK-large granular lymphocytic leukemia (NK-LGLL) is a rare chronic lymphoproliferative disorder and displays heterogeneity that remains insufficiently defined. CD56 plays a pivotal role in NK-cell maturation linked to cytotoxicity. However, whether CD56 might be associated with distinctive characteristics in NK-LGLL has not been determined. Hence, this study aims to explore potential associations between CD56 and clinical and biological features in 47 patients with NK-LGLL. Above all, anemia (57.4%) was the most prevalent symptom. Patients treated with immunosuppressive therapy showed a favorable outcome with 87.0% achieving remission. Furthermore, when stratifying patients by CD56 expression on tumor cells, the subset of 28 patients (59.6%) with diminished CD56 expression was frequently relevant to symptomatic disease (92.9% vs 15.8%, P < .001), comprising anemia (85.7% vs 15.8%, P < .001), neutropenia (67.9% vs 0.0%, P < .001), and splenomegaly (42.9% vs 10.5%, P = .024). Additionally, this subset demonstrated exclusive STAT3 mutation (61.9% vs 0.0%, P = .003), elevated CD161 levels (54.5% vs 0.0%, P < .001), and bone marrow fibrosis (92.3% vs 50.0%, P = 0.006). Furthermore, they showed shorter time to first treatment (TTFT) (4-year TTFT: 66.7% vs 100.0%, P = .083) and first-line progression-free survival (PFS) (median PFS: 26.3 months vs not reached, P = .112). Overall, our data indicate that NK-LGLL patients with diminished CD56 expression represent a more aggressive subset compared to those with normal CD56 levels, underscoring the significance of CD56 as a potential prognostic marker and advancing our understanding of the underlying pathogenesis of NK-LGLL.
自然杀伤细胞大颗粒淋巴细胞白血病（NK-LGLL）是一种罕见的慢性淋巴细胞增殖性疾病，具有异质性，目前仍未得到充分界定。CD56在与细胞毒性相关的自然杀伤细胞成熟过程中起关键作用。然而，CD56是否与NK-LGLL的独特特征相关尚未确定。因此，本研究旨在探讨47例NK-LGLL患者中CD56与临床及生物学特征之间的潜在关联。首先，贫血（57.4%）是最常见的症状。接受免疫抑制治疗的患者预后良好，87.0%的患者实现缓解。此外，根据肿瘤细胞上CD56的表达对患者进行分层时，28例（59.6%）CD56表达降低的患者亚组与症状性疾病密切相关（92.9%对15.8%，P<0.001），包括贫血（85.7%对15.8%，P<0.001）、中性粒细胞减少（67.9%对0.0%，P<0.001）和脾肿大（42.9%对10.5%，P=0.024）。此外，该亚组表现出独特的信号转导和转录激活因子3（STAT3）突变（61.9%对0.0%，P=0.003）、CD161水平升高（54.5%对0.0%，P<0.001）和骨髓纤维化（92.3%对50.0%，P=0.006）。此外，他们首次治疗的时间（TTFT）较短（4年TTFT：66.7%对100.0%，P=0.083），一线无进展生存期（PFS）也较短（中位PFS：26.3个月对未达到，P=0.112）。总体而言，我们的数据表明，与CD56水平正常的NK-LGLL患者相比，CD56表达降低的NK-LGLL患者代表了一个侵袭性更强的亚组，强调了CD56作为潜在预后标志物的重要性，并加深了我们对NK-LGLL潜在发病机制的理解。
