Marques Luísa Vieira Codeço, Noronha Elda Pereira, Andrade Francianne Gomes, Dos Santos-Bueno Filipe Vicente, Mansur Marcela B, Terra-Granado Eugenia, Pombo-de-Oliveira Maria S
Pediatric Hematology-Oncology Program, Research Center, Instituto Nacional do Câncer, Rio de Janeiro, Brazil.
Front Oncol. 2018 Oct 31;8:488. doi: 10.3389/fonc.2018.00488. eCollection 2018.
CD44 is a glycoprotein expressed in leucocytes and a marker of leukemia-initiating cells, being shown to be important in the pathogenesis of T cell acute lymphoblastic leukemia (T-ALL). In this study, we have (i) identified the aberrant antigenic pattern of CD44 and its isoform CD44v6 in T-ALL; (ii) tested the association with different T-cell subtypes and genomic alterations; (iii) identified the impact of CD44 status in T-ALL outcome. Samples from 184 patients (123 T-ALL and 61 AML; <19 years) were analyzed throughout multiparametric flow cytometry. Mutations in as well as and rearrangements were detected using standard molecular techniques. CD44 expression was characterized in all T-ALL and AML cases. Compared with AML samples in which the median fluorescence intensity (MFI) was 79.1 (1-1272), T-ALL was relatively low, with MFI 43.2 (1.9-1239); CD44v6 expression was rarely found, MFI 1 (0.3-3.7). T-ALL immature subtypes (mCD3/CD1a) had a lower CD44 expression, MFI 57.5 (2.7-866.3), whereas mCD3/TCRγδ cases had higher expressions, MFI 99.9 (16.4-866.3). and were associated with low CD44 expression, whereas and cases had intermediate expression. In relation to clinical features, CD44 expression was associated with tumor infiltrations ( = 0.065). However, no association was found with initial treatment responses and overall survival prediction. Our results indicate that CD44 is aberrantly expressed in T-ALL being influenced by different genomic alterations. Unraveling this intricate mechanism is required to place CD44 as a therapeutic target in T-ALL.
CD44是一种在白细胞中表达的糖蛋白,是白血病起始细胞的标志物,已被证明在T细胞急性淋巴细胞白血病(T-ALL)的发病机制中起重要作用。在本研究中,我们:(i)确定了T-ALL中CD44及其异构体CD44v6的异常抗原模式;(ii)测试了其与不同T细胞亚型和基因组改变的关联;(iii)确定了CD44状态对T-ALL预后的影响。通过多参数流式细胞术分析了184例患者(123例T-ALL和61例AML;年龄<19岁)的样本。使用标准分子技术检测了 以及 和 重排中的突变。对所有T-ALL和AML病例的CD44表达进行了表征。与AML样本(中位荧光强度[MFI]为79.1[1-1272])相比,T-ALL相对较低,MFI为43.2(1.9-1239);很少发现CD44v6表达,MFI为1(0.3-3.7)。T-ALL未成熟亚型(mCD3/CD1a)的CD44表达较低,MFI为57.5(2.7-866.3),而mCD3/TCRγδ病例的表达较高,MFI为99.9(16.4-866.3)。 和 与低CD44表达相关,而 和 病例表达中等。关于临床特征,CD44表达与肿瘤浸润相关( = 0.065)。然而,未发现与初始治疗反应和总生存预测相关。我们的结果表明,CD44在T-ALL中异常表达,受不同基因组改变的影响。需要阐明这种复杂机制,以便将CD44作为T-ALL的治疗靶点。