Department of Hematology, The Laboratory of Immunohematology, Aarhus University Hospital, Aarhus, Denmark.
Cytometry B Clin Cytom. 2012 Jan;82(1):3-8. doi: 10.1002/cyto.b.20614. Epub 2011 Aug 30.
Stable flow cytometric markers for malignant myeloid cells are highly warranted. Based on data from stem cell research, we hypothesized that the human inhibitory C-type lectin like receptor (hMICL) might represent a novel diagnostic and prognostic vehicle in a standard flow cytometry (FCM) setting.
Standard four-color FCM was employed to uncover the expression patterns of hMICL in bone marrow in a test set of 55 retrospectively collected diagnostic acute myeloid leukemia (AML) samples and in a set of 36 prospectively collected diagnostic AML samples.
Ninety-two percent of the AML patients stained positive for hMICL and in the otherwise poorly characterized CD34 negative patient group hMICL staining revealed a very homogenous expression profile in the blast cell compartment with a mean of 88% hMICL positive cells. Moreover, hMICL displayed significantly higher expression in AML as compared with normal donors as measured by median fluorescence intensity (MFI) ratios (P = 0.01). There was no difference in hMICL MFI ratios between the CD34 positive and the CD34 negative subgroups (P = 0.89). Importantly, there was no difference in MFI ratios between paired diagnostic and relapse samples (P = 0.76) in 23 cases studied, indicating stable expression of hMICL during the course of the disease. In contrast to the other stem cell associated antigens analyzed (CD34, CD96, CD117, and CD133), hMICL was expressed on myeloid blast cells only, revealing hMICL as a diagnostic marker in AML.
These data identify hMICL as a myeloid leukemia-associated antigen and establishes its applicability for diagnosis and follow-up of AML patients in a standard FCM setting.
恶性髓系细胞的稳定流式细胞术标志物是非常需要的。基于干细胞研究的数据,我们假设人抑制性 C 型凝集素样受体(hMICL)可能代表一种新的诊断和预后工具,可用于标准流式细胞术(FCM)设置。
采用标准四色 FCM 技术,在 55 例回顾性收集的诊断性急性髓系白血病(AML)样本的测试组和 36 例前瞻性收集的诊断性 AML 样本的测试组中,揭示 hMICL 在骨髓中的表达模式。
92%的 AML 患者 hMICL 染色阳性,在 otherwise poorly characterized CD34 negative 患者组中,hMICL 染色在 blast cell 区呈现出非常均匀的表达模式,平均有 88%的 hMICL 阳性细胞。此外,与正常供体相比,hMICL 在 AML 中的表达明显更高,中位荧光强度(MFI)比值(P = 0.01)。在 CD34 阳性和 CD34 阴性亚组之间,hMICL 的 MFI 比值没有差异(P = 0.89)。重要的是,在 23 例研究的病例中,配对诊断和复发样本之间的 MFI 比值没有差异(P = 0.76),表明 hMICL 在疾病过程中表达稳定。与分析的其他干细胞相关抗原(CD34、CD96、CD117 和 CD133)不同,hMICL 仅在髓系 blast 细胞上表达,揭示 hMICL 是 AML 的诊断标志物。
这些数据将 hMICL 鉴定为髓系白血病相关抗原,并在标准 FCM 环境中确立了其在 AML 患者诊断和随访中的应用。