Xuanmei Huang1, Libin Huang2, Qing Xie1, Ling Zhang3, Shaohui Huang1, Mingye Hong1, Jiangbin Li1, Zunnan Huang1, Hua Zhang4. 1. Institute of Laboratory Medicine, Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Key Laboratory of Big Data Mining and Precision Drug Design, School of Medical Technology, Guangdong Medical University, Guangdong Medical University, 523808, Dongguan, China. 2. Department of Pediatrics, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhong shan Er Lu, 510080, Guangzhou, China. 3. Health Science Center, The University of Texas, 77030, Houston, USA. 4. Institute of Laboratory Medicine, Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Key Laboratory of Big Data Mining and Precision Drug Design, School of Medical Technology, Guangdong Medical University, Guangdong Medical University, 523808, Dongguan, China. huazhang@gdmu.edu.cn.
Abstract
BACKGROUND: Although some studies have demonstrated that lncRNAs are dysregulated in hematopoietic malignancies and may regulate the progression of leukemia, the detailed mechanism underlying tumorigenesis is still unclear. This study aimed to investigate lncRNAs that are differentially expressed in childhood B-cell acute lymphoblastic leukemia (B-ALL) and T-cell acute lymphoblastic leukemia (T-ALL) and their potential roles in the progression of childhood ALL. METHODS: Microarrays were used to detect differentially expressed lncRNAs and mRNAs. Several aberrantly expressed lncRNAs were validated by qRT-PCR. Leukemia-free survival was analyzed using the Kaplan-Meier method with a log-rank test. The co-expression correlations of lncRNAs and mRNAs were determined by Spearman's correlation coefficient. CCK-8 assays and flow cytometry were performed to measure cell proliferation and apoptosis. RESULTS: We revealed that many lncRNAs were abnormally expressed in B-ALL and T-ALL. LncRNA/mRNA co-expression and the gene locus network showed that dysregulated lncRNAs are involved in diverse cellular processes. We also assessed the diagnostic value of the differentially expressed lncRNAs and confirmed the optimal combination of TCONS_00026679, uc002ubt.1, ENST00000411904, and ENST00000547644 with an area under the curve of 0.9686 [95 % CI: 0.9369-1.000, P < 0.001], with 90.7 % sensitivity and 92.19 % specificity, at a cut-off point of -0.5700 to distinguish childhood B-ALL patients from T-ALL patients, implying that these specific lncRNAs may have potential to detect subsets of childhood ALL. Notably, we found that the 8-year leukemia-free survival of patients with high TCONS_00026679 (p = 0.0081), ENST00000522339 (p = 0.0484), ENST00000499583 (p = 0.0381), ENST00000457217 (p = 0.0464), and ENST00000451368 (p = 0.0298) expression levels was significantly higher than that of patients with low expression levels of these lncRNAs, while patients with high uc002ubt.1 (p = 0.0499) and ENST00000547644 (p = 0.0451) expression levels exhibited markedly shorter 8-year leukemia-free survival. In addition, some lncRNAs were found to play different roles in cell proliferation and apoptosis in T-ALL and B-ALL. CONCLUSIONS: Dysregulated lncRNAs involved in different regulatory mechanisms underlying the progression of childhood T-ALL and B-ALL might serve as novel biomarkers to distinguish ALL subsets and indicate poor outcomes.
BACKGROUND: Although some studies have demonstrated that lncRNAs are dysregulated in hematopoietic malignancies and may regulate the progression of leukemia, the detailed mechanism underlying tumorigenesis is still unclear. This study aimed to investigate lncRNAs that are differentially expressed in childhood B-cell acute lymphoblastic leukemia (B-ALL) and T-cell acute lymphoblastic leukemia (T-ALL) and their potential roles in the progression of childhood ALL. METHODS: Microarrays were used to detect differentially expressed lncRNAs and mRNAs. Several aberrantly expressed lncRNAs were validated by qRT-PCR. Leukemia-free survival was analyzed using the Kaplan-Meier method with a log-rank test. The co-expression correlations of lncRNAs and mRNAs were determined by Spearman's correlation coefficient. CCK-8 assays and flow cytometry were performed to measure cell proliferation and apoptosis. RESULTS: We revealed that many lncRNAs were abnormally expressed in B-ALL and T-ALL. LncRNA/mRNA co-expression and the gene locus network showed that dysregulated lncRNAs are involved in diverse cellular processes. We also assessed the diagnostic value of the differentially expressed lncRNAs and confirmed the optimal combination of TCONS_00026679, uc002ubt.1, ENST00000411904, and ENST00000547644 with an area under the curve of 0.9686 [95 % CI: 0.9369-1.000, P < 0.001], with 90.7 % sensitivity and 92.19 % specificity, at a cut-off point of -0.5700 to distinguish childhood B-ALL patients from T-ALL patients, implying that these specific lncRNAs may have potential to detect subsets of childhood ALL. Notably, we found that the 8-year leukemia-free survival of patients with high TCONS_00026679 (p = 0.0081), ENST00000522339 (p = 0.0484), ENST00000499583 (p = 0.0381), ENST00000457217 (p = 0.0464), and ENST00000451368 (p = 0.0298) expression levels was significantly higher than that of patients with low expression levels of these lncRNAs, while patients with high uc002ubt.1 (p = 0.0499) and ENST00000547644 (p = 0.0451) expression levels exhibited markedly shorter 8-year leukemia-free survival. In addition, some lncRNAs were found to play different roles in cell proliferation and apoptosis in T-ALL and B-ALL. CONCLUSIONS: Dysregulated lncRNAs involved in different regulatory mechanisms underlying the progression of childhood T-ALL and B-ALL might serve as novel biomarkers to distinguish ALL subsets and indicate poor outcomes.
Authors: Phuong Cao Thi Ngoc; Shi Hao Tan; Tze King Tan; Min Min Chan; Zhenhua Li; Allen E J Yeoh; Daniel G Tenen; Takaomi Sanda Journal: Leukemia Date: 2018-03-26 Impact factor: 11.528
Authors: Yuhang Xiao; Ta Xiao; Wei Ou; Zhining Wu; Jie Wu; Jinming Tang; Bo Tian; Yong Zhou; Min Su; Wenxiang Wang Journal: Biomark Res Date: 2020-09-10