NK 淋巴母细胞白血病的临床、免疫表型和基因组学研究：来自骨髓病理学组的研究。

Clinical, immunophenotypic and genomic findings of NK lymphoblastic leukemia: a study from the Bone Marrow Pathology Group.

机构信息

Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Department of Pathology, Seattle Children's Hospital, Seattle, WA, USA.

出版信息

Mod Pathol. 2021 Jul;34(7):1358-1366. doi: 10.1038/s41379-021-00739-4. Epub 2021 Feb 1.

DOI:10.1038/s41379-021-00739-4

PMID:33526873

Abstract

Natural killer (NK) cells are lymphocytes of the native immune system that play a pivotal role in host defense and immune surveillance. While the conceptual view of NK-neoplasms is evolving, little is known about the rare NK lymphoblastic leukemia (NK-LL), which remains as a provisional entity in the 2016 WHO Classification. The goal of this study is to characterize NK-LL cases and compare with other CD56 co-expressing acute leukemias. We identified 105 cases, diagnosed as NK-LL (6), CD56+ acute undifferentiated leukemia (AUL) (6), CD56+ T-lymphoblastic leukemia (T-LL) (51), and CD56+ acute myeloid leukemia (AML) (42). Compared to AUL patients, NK-LL patients were significantly younger (p = 0.021) and presented with higher white blood cell (WBC) (p = 0.037) and platelet counts (p = 0.041). Flow cytometry showed more frequent expression of cytoplasmic CD3 (cCD3, p = 0.064) and CD33, (p = 0.065), while HLA-DR was significantly absent from NK-LL (p = 0.035) compared to AUL. Compared to T-ALL, NK-LL cases showed less frequent cCD3 (p = 0.002), CD4 (p = 0.051), and CD10 expression (p = 0.06). The frequency of abnormal karyotypes was similar between NK-LL, AUL, and T-ALL. The mutational profile differed in four leukemia groups, with a significance enrichment of NOTCH1 (p = 0.002), ETV6 (p = 0.002) and JAK3 (p = 0.02) mutations in NK-LL as compared to AML. As compared to T-ALL, NK-LL cases showed a higher number of total mutations (p = 0.04) and significantly more frequent ETV6 mutations (p = 0.004). Clinical outcome data showed differences in overall survival between all four groups (p = 0.0175), but no difference in event free survival (p = 0.246). In this largest study to date, we find that that NK-LL shows clinical presentation, immunophenotypic and molecular characteristics distinct from AUL, T-ALL, and AML. Our findings suggest NK-LL is a distinct acute leukemia entity and should be considered in the clinical diagnosis of acute leukemias of ambiguous lineage.

摘要

自然杀伤 (NK) 细胞是固有免疫系统的淋巴细胞，在宿主防御和免疫监视中发挥着关键作用。虽然 NK 肿瘤的概念正在不断发展，但对罕见的 NK 淋巴母细胞白血病 (NK-LL) 知之甚少，NK-LL 在 2016 年的 WHO 分类中仍然是一个暂定实体。本研究的目的是对 NK-LL 病例进行特征描述，并与其他共表达 CD56 的急性白血病进行比较。我们鉴定了 105 例 NK-LL（6 例）、CD56+急性未分化白血病（AUL）（6 例）、CD56+T 淋巴母细胞白血病（T-LL）（51 例）和 CD56+急性髓系白血病（AML）（42 例）。与 AUL 患者相比，NK-LL 患者明显更年轻（p=0.021），白细胞（WBC）计数更高（p=0.037），血小板计数更高（p=0.041）。流式细胞术显示更频繁的细胞质 CD3（cCD3，p=0.064）和 CD33 表达（p=0.065），而与 AUL 相比，HLA-DR 明显不存在于 NK-LL 中（p=0.035）。与 T-ALL 相比，NK-LL 病例的 cCD3（p=0.002）、CD4（p=0.051）和 CD10 表达频率较低（p=0.06）。NK-LL、AUL 和 T-ALL 之间的异常核型频率相似。四个白血病组的突变谱不同，与 AML 相比，NOTCH1（p=0.002）、ETV6（p=0.002）和 JAK3（p=0.02）突变在 NK-LL 中显著富集。与 T-ALL 相比，NK-LL 病例的总突变数更多（p=0.04），且 ETV6 突变更为频繁（p=0.004）。临床结果数据显示，四组患者的总生存期存在差异（p=0.0175），但无事件生存期无差异（p=0.246）。在这项迄今为止最大的研究中，我们发现 NK-LL 的临床表现、免疫表型和分子特征与 AUL、T-ALL 和 AML 不同。我们的研究结果表明 NK-LL 是一种独特的急性白血病实体，在急性白血病谱系不确定的临床诊断中应予以考虑。