PMID- 31475166 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220410 IS - 2305-5839 (Print) IS - 2305-5847 (Electronic) IS - 2305-5839 (Linking) VI - 7 IP - 14 DP - 2019 Jul TI - Genetic variants and clinical significance of pediatric acute lymphoblastic leukemia. PG - 296 LID - 10.21037/atm.2019.04.80 [doi] LID - 296 AB - BACKGROUND: Acute lymphoblastic leukemia (ALL), the most common childhood malignancy, is characterized by molecular aberrations. Recently, genetic profiling has been fully investigated on ALL; however, the interaction between its genetic alterations and clinical features is still unclear. Therefore, we investigated the effects of genetic variants on ALL phenotypes and clinical outcomes. METHODS: Targeted exome sequencing technology was used to detect molecular profiling of 140 Chinese pediatric patients with ALL. Correlation of genetic features and clinical outcomes was analyzed. RESULTS: T-cell ALL (T-ALL) patients had higher initial white blood cell (WBC) count (34.8x10(9)/L), higher incidence of mediastinal mass (26.9%), more relapse (23.1%), and enriched NOTCH1 (23.1%), FBXW7 (23.1%) and PHF6 (11.5%) mutations. Among the 18 recurrently mutated genes, SETD2 and TP53 mutations occurred more in female patients (P=0.041), NOTCH1 and SETD2 mutants were with higher initial WBC counts (>/=50x10(9)/L) (P=0.047 and P=0.041), JAK1 mutants were with higher minimal residual disease (MRD) level both on day 19 and day 46 (day 19 MRD >/=1%, P=0.039; day 46 MRD >/=0.01%, P=0.031) after induction chemotherapy. Multivariate analysis revealed that initial WBC counts (>/=50x10(9)/L), MLLr, and TP53 mutations were independent risk factors for 3-year relapse free survival (RFS) in ALL. Furthermore, TP53 mutations, age (<1 year or >/=10 years), and MLLr were independently associated with adverse outcome in B-cell ALL (B-ALL). CONCLUSIONS: MLLr and TP53 mutations are powerful predictors for adverse outcome in pediatric B-ALL and ALL. Genetic profiling can contribute to the improvement of prognostication and management in ALL patients. FAU - Zhang, Hong-Hong AU - Zhang HH AD - Department of Hematology and Oncology, Children's Hospital of Fudan University, Shanghai 201102, China. AD - Department of Pediatrics, Children's Hospital of Fudan University, Shanghai 201102, China. FAU - Wang, Hong-Sheng AU - Wang HS AD - Department of Hematology and Oncology, Children's Hospital of Fudan University, Shanghai 201102, China. AD - Department of Pediatrics, Children's Hospital of Fudan University, Shanghai 201102, China. FAU - Qian, Xiao-Wen AU - Qian XW AD - Department of Hematology and Oncology, Children's Hospital of Fudan University, Shanghai 201102, China. AD - Department of Pediatrics, Children's Hospital of Fudan University, Shanghai 201102, China. FAU - Fan, Cui-Qing AU - Fan CQ AD - Department of Pediatrics, Children's Hospital of Fudan University, Shanghai 201102, China. FAU - Li, Jun AU - Li J AD - Department of Hematology and Oncology, Children's Hospital of Fudan University, Shanghai 201102, China. AD - Department of Pediatrics, Children's Hospital of Fudan University, Shanghai 201102, China. FAU - Miao, Hui AU - Miao H AD - Department of Hematology and Oncology, Children's Hospital of Fudan University, Shanghai 201102, China. AD - Department of Pediatrics, Children's Hospital of Fudan University, Shanghai 201102, China. FAU - Zhu, Xiao-Hua AU - Zhu XH AD - Department of Hematology and Oncology, Children's Hospital of Fudan University, Shanghai 201102, China. AD - Department of Pediatrics, Children's Hospital of Fudan University, Shanghai 201102, China. FAU - Yu, Yi AU - Yu Y AD - Department of Hematology and Oncology, Children's Hospital of Fudan University, Shanghai 201102, China. AD - Department of Pediatrics, Children's Hospital of Fudan University, Shanghai 201102, China. FAU - Meng, Jian-Hua AU - Meng JH AD - Department of Hematology and Oncology, Children's Hospital of Fudan University, Shanghai 201102, China. AD - Department of Pediatrics, Children's Hospital of Fudan University, Shanghai 201102, China. FAU - Cao, Ping AU - Cao P AD - Department of Hematology and Oncology, Children's Hospital of Fudan University, Shanghai 201102, China. AD - Department of Pediatrics, Children's Hospital of Fudan University, Shanghai 201102, China. FAU - Le, Jun AU - Le J AD - Department of Hematology and Oncology, Children's Hospital of Fudan University, Shanghai 201102, China. AD - Department of Pediatrics, Children's Hospital of Fudan University, Shanghai 201102, China. FAU - Jiang, Jun-Ye AU - Jiang JY AD - Department of Hematology and Oncology, Children's Hospital of Fudan University, Shanghai 201102, China. AD - Department of Pediatrics, Children's Hospital of Fudan University, Shanghai 201102, China. FAU - Jiang, Wen-Jing AU - Jiang WJ AD - Department of Hematology and Oncology, Children's Hospital of Fudan University, Shanghai 201102, China. AD - Department of Pediatrics, Children's Hospital of Fudan University, Shanghai 201102, China. FAU - Wang, Ping AU - Wang P AD - Department of Hematology and Oncology, Children's Hospital of Fudan University, Shanghai 201102, China. AD - Department of Pediatrics, Children's Hospital of Fudan University, Shanghai 201102, China. FAU - Zhai, Xiao-Wen AU - Zhai XW AD - Department of Hematology and Oncology, Children's Hospital of Fudan University, Shanghai 201102, China. AD - Department of Pediatrics, Children's Hospital of Fudan University, Shanghai 201102, China. LA - eng PT - Journal Article PL - China TA - Ann Transl Med JT - Annals of translational medicine JID - 101617978 PMC - PMC6694231 OTO - NOTNLM OT - Acute lymphoblastic leukemia (ALL) OT - clinical significance OT - genetic variants OT - next-generation sequencing (NGS) OT - pediatric COIS- Conflicts of Interest: The authors have no conflicts of interest to declare. EDAT- 2019/09/03 06:00 MHDA- 2019/09/03 06:01 PMCR- 2019/07/01 CRDT- 2019/09/03 06:00 PHST- 2019/09/03 06:00 [entrez] PHST- 2019/09/03 06:00 [pubmed] PHST- 2019/09/03 06:01 [medline] PHST- 2019/07/01 00:00 [pmc-release] AID - atm-07-14-296 [pii] AID - 10.21037/atm.2019.04.80 [doi] PST - ppublish SO - Ann Transl Med. 2019 Jul;7(14):296. doi: 10.21037/atm.2019.04.80.