文章：

CD33和CD123在急性髓性白血病细胞表面表达的分布和水平

Distribution and levels of cell surface expression of CD33 and CD123 in acute myeloid leukemia

原文发布日期：2014-06-13

DOI: 10.1038/bcj.2014.39

类型: Original Article

开放获取: 是

英文摘要：

Owing to the more recent positive results with the anti-CD33 immunotoxin gemtuzumab ozogamicin, therapy against acute myeloid leukemias (AMLs) targeting CD33 holds many promises. Here, CD33 and CD123 expression on AML blasts was studied by flow cytometry in a cohort of 319 patients with detailed information on French–American–British/World Health Organization (FAB/WHO) classification, cytogenetics and molecular aberrations. AMLs of 87.8% express CD33 and would therefore be targetable with anti-CD33 therapies. Additionally, 9.4% of AMLs express CD123 without concomitant CD33 expression. Thus, nearly all AMLs could be either targeted via CD33 or CD123. Simultaneous presence of both antigens was observed in 69.5% of patients. Most importantly, even AMLs with adverse cytogenetics express CD33 and CD123 levels comparable to those with favorable and intermediate subtypes. Some patient groups with unfavorable alterations, such as FMS-related tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutations, high FLT3-ITD mutant/wild-type ratios and monosomy 5 are even characterized by high expression of CD33 and CD123. In addition, blasts of patients with mutant nucleophosmin (NPM1) revealed significantly higher CD33 and CD123 expression pointing toward the possibility of minimal residual disease-guided interventions in mutated NPM1-positive AMLs. These results stimulate the development of novel concepts to redirect immune effector cells toward CD33- and CD123-expressing blasts using bi-specific antibodies or engineered T cells expressing chimeric antigen receptors.

摘要翻译： 

由于抗CD33免疫毒素吉妥珠单抗奥佐米星近期取得了积极成果，针对CD33的急性髓系白血病（AML）疗法展现出广阔前景。本研究通过流式细胞术检测了319例患者AML原始细胞中CD33和CD123的表达情况，这些患者均具有详细的法美英（FAB）/世界卫生组织（WHO）分型、细胞遗传学和分子异常信息。87.8%的AML表达CD33，因此可成为抗CD33疗法的靶点。此外，9.4%的AML在不表达CD33的同时表达CD123。这意味着近所有AML均可通过CD33或CD123进行靶向治疗。69.5%的患者同时存在这两种抗原。最重要的是，即使是不良细胞遗传学的AML，其CD33和CD123表达水平也与良好和中危亚型相当。某些具有不利突变（如FLT3-ITD突变、高FLT3-ITD突变/野生型比值及5号染色体单体）的患者群体甚至呈现CD33和CD123的高表达特征。此外，突变型核磷蛋白（NPM1）患者的原始细胞显示显著更高的CD33和CD123表达，这为突变NPM1阳性AML开展微小残留病指导的干预措施提供了可能。这些结果推动了新疗法的研发方向，包括使用双特异性抗体或表达嵌合抗原受体的工程化T细胞将免疫效应细胞重定向至CD33和CD123表达的原始细胞。

原文链接：

Distribution and levels of cell surface expression of CD33 and CD123 in acute myeloid leukemia