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Genomic Profiling of Adult and Pediatric B-cell Acute Lymphoblastic Leukemia

2016; Elsevier BV; Volume: 8; Linguagem: Inglês

10.1016/j.ebiom.2016.04.038

2352-3964

Yuanfang Liu, Baiyan Wang, Weina Zhang, Jinyan Huang, Ben-Shang Li, Ming Zhang, Lu Jiang, Jianfeng Li, Mingjie Wang, Yu‐Jun Dai, Ziguan Zhang, Qiang Wang, Jie Kong, Bing Chen, Yong‐Mei Zhu, Xiangqin Weng, Zhi-Xiang Shen, Junmin Li, Jin Wang, Xiaojing Yan, Yan Li, Yingmin Liang, Li Liu, Xiequn Chen, Wanggang Zhang, Jinsong Yan, Jianda Hu, Shuhong Shen, Jing Chen, Long-Jun Gu, Deqing Pei, Yongjin Li, Gang Wu, Xin Zhou, Ruibao Ren, Cheng Cheng, Jinsong Yan, Kankan Wang, Shengyue Wang, Jinghui Zhang, Jian‐Qing Mi, Ching‐Hon Pui, Jingyan Tang, Chen Zhu, Sai‐Juan Chen,

Chronic Myeloid Leukemia Treatments

Genomic landscapes of 92 adult and 111 pediatric patients with B-cell acute lymphoblastic leukemia (B-ALL) were investigated using next-generation sequencing and copy number alteration analysis. Recurrent gene mutations and fusions were tested in an additional 87 adult and 93 pediatric patients. Among the 29 newly identified in-frame gene fusions, those involving MEF2D and ZNF384 were clinically relevant and were demonstrated to perturb B-cell differentiation, with EP300-ZNF384 inducing leukemia in mice. Eight gene expression subgroups associated with characteristic genetic abnormalities were identified, including leukemia with MEF2D and ZNF384 fusions in two distinct clusters. In subgroup G4 which was characterized by ERG deletion, DUX4-IGH fusion was detected in most cases. This comprehensive dataset allowed us to compare the features of molecular pathogenesis between adult and pediatric B-ALL and to identify signatures possibly related to the inferior outcome of adults to that of children. We found that, besides the known discrepancies in frequencies of prognostic markers, adult patients had more cooperative mutations and greater enrichment for alterations of epigenetic modifiers and genes linked to B-cell development, suggesting difference in the target cells of transformation between adult and pediatric patients and may explain in part the disparity in their responses to treatment.