目的:本研究旨在回顾性评估C-凝集素样分子1(CLL-1)在急性髓系白血病(AML)患者(总N=306)CD34+母细胞上的双峰表达,并探讨CLL-1双峰与白血病和患者特异性特征的潜在关联。
方法:进行流式细胞术测定以评估CLL-1双峰性的深层免疫表型。进行细胞遗传学分析以表征CLL-1双峰AML样品的CLL-1阴性亚群上的基因突变。
结果:在不同的队列中,CD34+母细胞的CLL-1表达的双峰模式的频率范围为8%至65%。双峰CLL-1表达在MDS相关AML患者中最为普遍(P=0.011),ELN不利风险(P=.002),NPM1野生型(WT,P=.049),FLT3WT(P=.035),白血病相关免疫表型的百分比相对较低(P=.006)。其他免疫表型分析显示,CLL-1-亚群可能由前B细胞组成,未成熟的成髓细胞,和造血干细胞。此外,在双峰样品的CLL-1+和CLL-1-亚组分中均检测到(前)-白血病突变(N=3)。
结论:约25%的AML患者存在C-凝集素样分子1双峰性,CLL-1-细胞群仍含有恶性细胞,因此,这可能会限制CLL-1靶向治疗的有效性,需要进一步研究.
OBJECTIVE: This study aims to retrospectively assess C-lectin-like molecule 1 (CLL-1) bimodal expression on CD34+ blasts in acute myeloid leukemia (AML) patients (total N = 306) and explore potential CLL-1 bimodal associations with leukemia and patient-specific characteristics.
METHODS: Flow cytometry assays were performed to assess the deeper immunophenotyping of CLL-1 bimodality. Cytogenetic analysis was performed to characterize the gene mutation on CLL-1-negative subpopulation of CLL-1 bimodal AML samples.
RESULTS: The frequency of a bimodal pattern of CLL-1 expression of CD34+ blasts ranged from 8% to 65% in the different cohorts. Bimodal CLL-1 expression was most prevalent in patients with MDS-related AML (P = .011), ELN adverse risk (P = .002), NPM1 wild type (WT, P = .049), FLT3 WT (P = .035), and relatively low percentages of leukemia-associated immunophenotypes (P = .006). Additional immunophenotyping analysis revealed the CLL-1- subpopulation may consist of pre-B cells, immature myeloblasts, and hematopoietic stem cells. Furthermore, (pre)-leukemic mutations were detected in both CLL-1+ and CLL-1- subfractions of bimodal samples (N = 3).
CONCLUSIONS: C-lectin-like molecule 1 bimodality occurs in about 25% of AML patients and the CLL-1- cell population still contains malignant cells, hence it may potentially limit the effectiveness of CLL-1-targeted therapies and warrant further investigation.