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儿童急性淋巴细胞白血病诊断及临床缓解期骨髓和外周血单个核细胞中唾液酸与黏附分子差异表达的比较分析

Comparative analysis of differential expression of sialic acids and adhesion molecules on mononuclear cells of bone marrow and peripheral blood in childhood acute lymphoblastic leukaemia at diagnosis and clinical remission.

作者信息

Chowdhury Suchandra, Bandyopadhyay Suman, Chandra Sarmila, Mandal Chitra

机构信息

Infectious Disease and Immunology Division, Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Kolkata 700032, India.

出版信息

Indian J Biochem Biophys. 2007 Oct;44(5):357-65.

Abstract

Childhood acute lymphoblastic leukaemia (ALL) is characterized by the neoplasm of immature haematopoietic precursor cells (HPCs). We report significant differences between the expression of sialoglycoproteins and adhesion molecules on mononuclear cells (MNCs) of bone marrow (BM) and peripheral blood (PB) from individual children at diagnosis of the disease. Lymphoblasts in PB predominantly expressed 9-O-acetylated sialoglycoproteins (Neu5,9Ac2-GPs), sialic acid, alpha2-3 linked sialic acid, L- and P-selectins and vascular cell adhesion molecule -1 (VCAM-1) on their surface compared to BM, as determined with selective lectins and monoclonal antibodies (mAbs) by flow cytometric analysis. CD34+CD38+ cells present either in diagnostic PB or BM always showed enhanced expression of both alpha2-3 and alpha2-6 linked sialic acids, Neu5,9Ac2-GPs, L- and P-selectins and VCAM-1, compared to CD34+CD38- population, as confirmed by higher mean fluorescence intensity (MFI). Expression of ICAM-1 was reverse. However, MFI of Neu5,9Ac2-GPs was always higher both in CD34+CD38+ and CD34+CD38- population in PB compared to BM. Diverse trend of these cell surface macromolecules was observed during clinical remission. This is the first comparative study between PB and BM, where significant differential distribution of sialylated macromolecules and adhesion molecules was observed. Hence, supervising these cell surface macromolecules at various stages of treatment might help in minimal residual disease detection, identifying mobilization factor(s) and in isolation of normal HPCs for autologous BM transplantation.

摘要

儿童急性淋巴细胞白血病(ALL)的特征是未成熟造血前体细胞(HPCs)的肿瘤形成。我们报告了在疾病诊断时,个别儿童骨髓(BM)和外周血(PB)单核细胞(MNCs)上唾液酸糖蛋白和黏附分子表达的显著差异。通过流式细胞术分析,使用选择性凝集素和单克隆抗体(mAbs)测定,与BM相比,PB中的淋巴母细胞表面主要表达9-O-乙酰化唾液酸糖蛋白(Neu5,9Ac2-GPs)、唾液酸、α2-3连接的唾液酸、L-和P-选择素以及血管细胞黏附分子-1(VCAM-1)。诊断性PB或BM中存在的CD34+CD38+细胞与CD34+CD38-群体相比,总是显示出α2-3和α2-6连接的唾液酸、Neu5,9Ac2-GPs、L-和P-选择素以及VCAM-1的表达增强,这通过更高的平均荧光强度(MFI)得到证实。细胞间黏附分子-1(ICAM-1)的表达则相反。然而,与BM相比,PB中CD34+CD38+和CD34+CD38-群体中Neu5,9Ac2-GPs的MFI始终更高。在临床缓解期间观察到这些细胞表面大分子的不同变化趋势。这是首次对PB和BM进行的比较研究,观察到唾液酸化大分子和黏附分子存在显著的差异分布。因此,在治疗的各个阶段监测这些细胞表面大分子可能有助于微小残留病的检测、识别动员因子以及分离正常HPCs用于自体骨髓移植。

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