Vanhooren Jolien, Van Camp Laurens, Depreter Barbara, de Jong Martijn, Uyttebroeck Anne, Van Damme An, Dedeken Laurence, Dresse Marie-Françoise, van der Werff Ten Bosch Jutte, Hofmans Mattias, Philippé Jan, De Moerloose Barbara, Lammens Tim
Department of Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent University Hospital, 9000 Ghent, Belgium.
Department of Internal Medicine and Pediatrics, Ghent University, 9000 Ghent, Belgium.
Cancers (Basel). 2022 Apr 22;14(9):2098. doi: 10.3390/cancers14092098.
Pediatric acute myeloid leukemia (pedAML) is a heterogeneous blood cancer that affects children. Although survival rates have significantly improved over the past few decades, 20-30% of children will succumb due to treatment-related toxicity or relapse. The molecular characterization of the leukemic stem cell, shown to be responsible for relapse, is needed to improve treatment options and survival. Recently, it has become clear that non-coding RNAs, including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), play a role in the development of human diseases, including pediatric cancer. Nevertheless, non-coding RNA expression data in pedAML are scarce. Here, we explored lncRNA ( = 30,168) and miRNA ( = 627) expression in pedAML subpopulations (leukemic stem cells (LSCs) and leukemic blasts (L-blasts)) and their normal counterparts (hematopoietic stem cells and control myeloblasts). The potential regulatory activity of differentially expressed lncRNAs in LSCs (unique or shared with the L-blast comparison) on miRNAs was assessed. Moreover, pre-ranked gene set enrichment analyses of (anti-) correlated protein-coding genes were performed to predict the functional relevance of the differentially upregulated lncRNAs in LSCs (unique or shared with the L-blast comparison). In conclusion, this study provides a catalog of non-coding RNAs with a potential role in the pathogenesis of pedAML, paving the way for further translational research studies.
小儿急性髓系白血病（pedAML）是一种影响儿童的异质性血癌。尽管在过去几十年中生存率有了显著提高，但仍有20% - 30%的儿童会因治疗相关毒性或复发而死亡。为了改善治疗方案和提高生存率，需要对导致复发的白血病干细胞进行分子特征分析。最近，包括长链非编码RNA（lncRNA）和微小RNA（miRNA）在内的非编码RNA在包括小儿癌症在内的人类疾病发展中所起的作用已变得清晰。然而，pedAML中的非编码RNA表达数据却很稀少。在此，我们探究了pedAML亚群（白血病干细胞（LSCs）和白血病母细胞（L - blasts））及其正常对应物（造血干细胞和对照成髓细胞）中的lncRNA（n = 30,168）和miRNA（n = 627）表达。评估了LSCs中差异表达的lncRNAs（与L - blasts比较中独特的或共有的）对miRNAs的潜在调控活性。此外，对（反）相关蛋白质编码基因进行预排序的基因集富集分析，以预测LSCs中差异上调的lncRNAs（与L - blasts比较中独特的或共有的）的功能相关性。总之，本研究提供了一份在pedAML发病机制中可能起作用的非编码RNA目录，为进一步的转化研究铺平了道路。
