Alsuwaidi Laila, Hachim Mahmood, Senok Abiola
College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates.
Center for Genomic Discovery, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates.
Front Cell Dev Biol. 2021 Jun 25;9:706129. doi: 10.3389/fcell.2021.706129. eCollection 2021.
The extensive genetic heterogeneity found in the B cell precursor acute lymphoblastic leukemia (BCP-ALL) subtype of childhood ALL represents a potential repository of biomarkers. To explore this potential, we have carried out analysis of publicly available ALL datasets to identify genetic biomarkers for childhood BCP-ALL, which could be used either individually or in combination as markers for early detection, risk stratification, and prognosis.
To explore novel genes that show promising clinical and molecular signatures, we examined the cBioPortal online tool for publicly available datasets on lymphoid cancers. Three studies on lymphoblastic and lymphoid leukemia with 1706 patients and 2144 samples of which were identified. Only B-Lymphoblastic Leukemia/Lymphoma samples ( = 1978) were selected for further analysis. Chromosomal changes were assessed to determine novel genomic loci to analyze clinical and molecular profiles for the leukemia of lymphoid origin using cBioPortal tool.
ADAM6 gene homozygous deletions (HOM:DEL) were present in 59.60% of the profiled patients and were associated with poor ten years of overall patients' survival. Moreover, patients with ADAM6 HOM:DEL showed a distinguished clinical and molecular profile with higher Central Nervous System (CNS) sites of relapse. In addition, ADAM6 HOM:DEL was significantly associated with unique microRNAs gene expression patterns.
ADAM6 has the potential to be a novel biomarker for the development and progress of BCP- ALL.
儿童急性淋巴细胞白血病(ALL)的B细胞前体急性淋巴细胞白血病(BCP-ALL)亚型中发现的广泛遗传异质性代表了一个潜在的生物标志物库。为了探索这一潜力,我们对公开可用的ALL数据集进行了分析,以确定儿童BCP-ALL的遗传生物标志物,这些标志物可单独或联合用作早期检测、风险分层和预后的标志物。
为了探索显示出有前景的临床和分子特征的新基因,我们使用cBioPortal在线工具检查了关于淋巴癌的公开可用数据集。确定了三项关于淋巴细胞白血病和淋巴白血病的研究,涉及1706例患者和2144个样本。仅选择B淋巴细胞白血病/淋巴瘤样本(=1978)进行进一步分析。使用cBioPortal工具评估染色体变化,以确定新的基因组位点,分析淋巴源性白血病的临床和分子特征。
在59.60%的分析患者中存在ADAM6基因纯合缺失(HOM:DEL),且与患者总体十年生存率低相关。此外,ADAM6 HOM:DEL患者表现出独特的临床和分子特征,中枢神经系统(CNS)复发部位更高。此外,ADAM6 HOM:DEL与独特的微小RNA基因表达模式显著相关。
ADAM6有潜力成为BCP-ALL发生和进展的新型生物标志物。