Therapy-induced mutations drive the genomic landscape of relapsed acute lymphoblastic leukemia

• DOI: 10.1182/blood.2019002220
• Publication Date: 2019-10-24T18:43:06Z
• Authors: Benshang Li; Samuel W. Brady; Xiaotu Ma; Shuhong Shen; Yingchi Zhang; Yongjin Li; Karol Szlachta; Li Dong; Yu Liu; Fan Yang; Ningling Wang; Diane A. Flasch; Matthew A. Myers; Heather L. Mulder; Lixia Ding; Yanling Liu; Liqing Tian; Kohei Hagiwara; Ke Xu; Xin Zhou; Edgar Sioson; Tianyi Wang; Liu Yang; Jie Zhao; Hui Zhang; Ying Shao; Hongye Sun; Lele Sun; Jiaoyang Cai; Hui-Ying Sun; Ting-Nien Lin; Lijuan Du; Hui Li; Michael Rusch; Michael N. Edmonson; John Easton; Xiaofan Zhu; Jingliao Zhang; Cheng Cheng; Benjamin J. Raphael; Jingyan Tang; James R. Downing; Ludmil B. Alexandrov; Bin-Bing S. Zhou; Ching-Hon Pui; Jun J. Yang; Jinghui Zhang
• Keywords: Male; 0301 basic medicine; Antimetabolites, Antineoplastic; DNA Mutational Analysis; High-Throughput Nucleotide Sequencing; Genomics; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; 3. Good health; Survival Rate; 03 medical and health sciences; Methotrexate; Receptors, Glucocorticoid; Mutagenesis; Mutation; Biomarkers, Tumor; Humans; Female; Tumor Suppressor Protein p53; Child; 5'-Nucleotidase; Follow-Up Studies

Li and colleagues report the genomic landscape of over 100 patients with relapsed acute lymphoblastic leukemia. Analysis of diagnosis-relapse-remission trios suggest that whereas early relapse is mediated by retained subclones, late relapse is driven by mutations induced by and conferring resistance to chemotherapy.