Van Camp Laurens, Depreter Barbara, De Wilde Jilke, Hofmans Mattias, Van der Linden Malaïka, Terras Eva, Chantrain Christophe, Dedeken Laurence, Van Damme An, Uyttebroeck Anne, Lammens Tim, De Moerloose Barbara
Ghent University, Department of Internal Medicine and Pediatrics, Ghent, Belgium.
Ghent University Hospital, Department of Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent, Belgium.
Pediatr Res. 2025 Jan;97(1):160-168. doi: 10.1038/s41390-024-03341-x. Epub 2024 Jun 15.
Relapse in pediatric acute myeloid leukemia (pedAML) patients is known to be associated with residual leukemic stem cells (LSC). We have previously shown that epithelial membrane protein 1 (EMP1) is significantly overexpressed in LSC compared to hematological stem cell fractions. EMP1 was also documented as part of the 17-gene stemness score and a 6-membrane protein gene score, both correlating high EMP1 expression with worse overall survival. However, its potential as a therapeutic target in pedAML is still unexplored.
Association analyses of EMP1 expression with clinical and molecular AML characteristics were performed. Expression of EMP1 was evaluated in pedAML and cord blood samples. Expression in normal blood cells and tissues was evaluated by flow cytometry and immunohistochemistry, respectively.
In silico analyses showed variable mRNA expression of EMP1 in multiple pedAML datasets, and a significant correlation between high EMP1 transcript levels and the presence of inv(16). Flow cytometry showed overexpression of EMP1 in pedAML samples, as well as expression in normal blood subsets. Importantly, immunohistochemistry revealed EMP1 expression in multiple normal tissues.
Although EMP1 presents as an interesting membrane-associated target in pedAML, its abundant expression in normal blood cells and tissues will impede it from further exploration as a therapeutic target.
EMP1 is highly expressed in multiple cancer types, but expression in acute myeloid leukemia (AML) and normal tissues is unexplored. As EMP1 is investigated in other cancer types, expression in normal tissues and blood cells is relevant in predicting the success of EMP1-targeted therapies. In this study, we showed expression of EMP1 in multiple tissues, predicting high on-target off-tumor toxicity, which will warn other researchers of possible toxicities when generating EMP1-targeted therapy. Finally, we showed that high EMP1 expression is associated with better overall survival of pediatric AML patients, reducing the need for EMP1-targeted therapy.
已知小儿急性髓系白血病（pedAML）患者的复发与残留白血病干细胞（LSC）有关。我们之前已经表明，与血液干细胞组分相比，上皮膜蛋白1（EMP1）在LSC中显著过表达。EMP1也被记录为17基因干性评分和6膜蛋白基因评分的一部分，这两个评分都将高EMP1表达与较差的总生存期相关联。然而，其作为pedAML治疗靶点的潜力仍未得到探索。
进行了EMP1表达与临床和分子AML特征的关联分析。在pedAML和脐带血样本中评估EMP1的表达。分别通过流式细胞术和免疫组织化学评估其在正常血细胞和组织中的表达。
计算机分析显示，在多个pedAML数据集中，EMP1的mRNA表达存在差异，并且高EMP1转录水平与inv(16)的存在之间存在显著相关性。流式细胞术显示pedAML样本中EMP1过表达，以及在正常血液亚群中的表达。重要的是，免疫组织化学显示EMP1在多个正常组织中表达。
尽管EMP1在pedAML中表现为一个有趣的膜相关靶点，但其在正常血细胞和组织中的丰富表达将阻碍其作为治疗靶点进一步探索。
EMP1在多种癌症类型中高表达，但在急性髓系白血病（AML）和正常组织中的表达尚未得到研究。由于正在其他癌症类型中研究EMP1，正常组织和血细胞中的表达对于预测EMP1靶向治疗的成功至关重要。在本研究中，我们显示了EMP1在多个组织中的表达，预测了高靶点外肿瘤毒性，这将提醒其他研究人员在产生EMP1靶向治疗时可能存在的毒性。最后，我们表明高EMP1表达与小儿AML患者更好的总生存期相关，减少了对EMP1靶向治疗的需求。
