Buono Lorena, Iside Concetta, De Matteo Antonia, Stellato Pio, Beneduce Giuliana, de Vera d'Aragona Roberta Penta, Parasole Rosanna, Salvatore Marco, Smaldone Giovanni, Mirabelli Peppino
IRCCS SYNLAB SDN, Via E. Gianturco 113, 80413, Naples, Italy.
Santobono-Pausilipon Children's Hospital, AORN, Naples, Italy.
Cancer Cell Int. 2022 Nov 30;22(1):373. doi: 10.1186/s12935-022-02789-3.
Long non-coding RNAs are RNAs longer than 200 bps that do not encode any proteins and are able to alter gene expression by acting on different steps of regulation, including DNA methylation and chromatin structure. They represent a class of biomarkers of crescent interest in the hematologic and oncologic fields. Recent studies showed that the expression levels of specific lncRNAs correlate with the prognosis of paediatric patients with Acute Lymphoblastic Leukaemia.
We used NGS approaches to analyse the transcriptome of 9 childhood B-ALL patients and 6 childhood T-ALL patients, in comparison with B and T healthy lymphocytes from cord blood. We validate our findings both ex vivo, in a different cohort of 10 B-ALL and 10 T-ALL patients, and in silico using public datasets.
We characterised the lncRNA landscape for B-ALL, T-ALL, healthy B, and T cell progenitors. From the characterised signature, we selected candidate lncRNAs able to discriminate not only B-ALL and T-ALL from healthy subjects but also between the two types of leukaemia, and subsequently validated their potential as a diagnostic tool in an additional cohort of paediatric patients. We confirmed our finding with open access transcriptomic data, comparing ALL lncRNAs with AML lncRNA landscape as well. Finally, expression correlation analyses of T-ALL selected lncRNA biomarkers suggested a possible role in lymphocyte activation and the β-catenin signalling pathway for AC247036.1 and involvement in hedgehog signalling for HHIP-AS1.
Our work identified a lncRNA signature discriminating paediatric B-ALL and T-ALL from healthy subjects, between them and from AML. This study provides the keystone to future clinical studies determining the theragnostic value of the characterised long non coding transcriptome panorama in a clinical setting for childhood patient management.
长链非编码RNA是长度超过200个碱基对的RNA，不编码任何蛋白质，能够通过作用于包括DNA甲基化和染色质结构在内的不同调控步骤来改变基因表达。它们是血液学和肿瘤学领域中一类越来越受关注的生物标志物。最近的研究表明，特定长链非编码RNA的表达水平与小儿急性淋巴细胞白血病患者的预后相关。
我们使用NGS方法分析了9例儿童B细胞急性淋巴细胞白血病患者和6例儿童T细胞急性淋巴细胞白血病患者的转录组，并与来自脐带血的健康B淋巴细胞和T淋巴细胞进行了比较。我们在另一组10例B细胞急性淋巴细胞白血病患者和10例T细胞急性淋巴细胞白血病患者中进行了体外验证，并使用公共数据集进行了计算机模拟验证。
我们描绘了B细胞急性淋巴细胞白血病、T细胞急性淋巴细胞白血病、健康B细胞和T细胞祖细胞的长链非编码RNA图谱。从所描绘的特征中，我们选择了不仅能够区分健康受试者的B细胞急性淋巴细胞白血病和T细胞急性淋巴细胞白血病，而且能够区分这两种白血病类型的候选长链非编码RNA，随后在另一组小儿患者中验证了它们作为诊断工具的潜力。我们通过开放获取的转录组数据证实了我们的发现，并将所有急性淋巴细胞白血病的长链非编码RNA与急性髓细胞白血病的长链非编码RNA图谱进行了比较。最后，对T细胞急性淋巴细胞白血病选择的长链非编码RNA生物标志物的表达相关性分析表明，AC247036.1可能在淋巴细胞激活和β-连环蛋白信号通路中起作用，而HHIP-AS1参与刺猬信号通路。
我们的工作确定了一种长链非编码RNA特征，可区分小儿B细胞急性淋巴细胞白血病和T细胞急性淋巴细胞白血病与健康受试者，以及它们与急性髓细胞白血病的差异。这项研究为未来的临床研究奠定了基础，这些研究将确定所描绘的长链非编码转录组全景在儿童患者临床管理中的治疗诊断价值。
