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Chondroitin Sulfate Proteoglycan-4 (CSPG4)-Specific Monoclonal Antibody 225.28 in Detection of Acute Myeloid Leukemia Blasts

机译:硫酸软骨素蛋白聚糖-4(CSPG4)特异的单克隆抗体225.28在检测急性髓细胞白血病的细胞中。

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Chondroitin sulfate proteoglycan-4 (CSPG4), a membrane-bound proteoglycan known to be expressed on the surface of malignant cells, has a restricted distribution in normal tissues. CSPG4 is a potential candidate tumor marker. We investigate CSPG4 expression on blasts in newly diagnosed acute myeloid leukemia (AML) patients and its relation with cytogenetic abnormalities and molecular markers known to have prognostic significance in this disease. Using hybridoma technology, we generated a specific monoclonal antibody (mAb), mAb 225.28, reactive with CSPG4. Blast samples obtained from the peripheral blood of newly diagnosed AML patients were analyzed for CSPG4 expression using the CSPG4-specific mAb and multiparameter flow cytometry. The results were correlated with cytogenetic and molecular characteristics of AML. CSPG4 was found to be expressed on a variable fraction of leukemic blasts in all AML patients with different leukemia morphology, including monoblastic cases. Reactivity of CSPG4-specific mAb with leukemic blasts was not limited to those with the rearranged MLL gene. CSPG4 was also expressed on AML blasts with a complex karyotype, FLT3 mutation, or NPM1 mutation. The results indicate that CSPG4 is expressed and detectable by flow cytometry using the mAb 225.28 on a proportion of blasts of all subtypes of AML irrespective of cytogenetic and molecular abnormalities. mAb 225.28 could be useful in detecting AML blasts by flow cytometry.
机译:硫酸软骨素蛋白聚糖-4(CSPG4)是一种已知在恶性细胞表面表达的膜结合蛋白聚糖,在正常组织中分布受限。 CSPG4是潜在的候选肿瘤标志物。我们调查了CSPG4在新诊断的急性髓细胞性白血病(AML)患者的母细胞中的表达及其与细胞遗传异常和已知对该疾病具有预后意义的分子标志物的关系。使用杂交瘤技术,我们生成了与CSPG4反应的特异性单克隆抗体(mAb)mAb 225.28。使用CSPG4特异性mAb和多参数流式细胞术分析从新诊断的AML患者外周血中获得的冲击波样品的CSPG4表达。结果与AML的细胞遗传学和分子特征相关。发现在所有具有不同白血病形态的AML患者(包括单核细胞病例)中,CSPG4均在可变比例的白血病母细胞中表达。 CSPG4特异性mAb与白血病母细胞的反应性不仅限于重排的MLL基因。 CSPG4还可以在具有复杂核型,FLT3突变或NPM1突变的AML母细胞上表达。结果表明CSPG4可以通过使用mAb 225.28的流式细胞术在一定比例的AML所有亚型胚泡中表达和检测,而与细胞遗传学和分子异常无关。 mAb 225.28可用于通过流式细胞术检测AML原始细胞。

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