PMID- 35963521 OWN - NLM STAT- MEDLINE DCOM- 20221107 LR - 20231102 IS - 1943-7811 (Electronic) IS - 1525-1578 (Print) IS - 1525-1578 (Linking) VI - 24 IP - 11 DP - 2022 Nov TI - Sequential Approach to Improve the Molecular Classification of Childhood Acute Lymphoblastic Leukemia. PG - 1195-1206 LID - S1525-1578(22)00220-3 [pii] LID - 10.1016/j.jmoldx.2022.08.001 [doi] AB - Identification of specific leukemia subtypes is a key to successful risk-directed therapy in childhood acute lymphoblastic leukemia (ALL). Although RNA sequencing (RNA-seq) is the best approach to identify virtually all specific leukemia subtypes, the routine use of this method is too costly for patients in resource-limited countries. This study enrolled 295 patients with pediatric ALL from 2010 to 2020. Routine screening could identify major cytogenetic alterations in approximately 69% of B-cell ALL (B-ALL) cases by RT-PCR, DNA index, and multiplex ligation-dependent probe amplification. STIL-TAL1 was present in 33% of T-cell ALL (T-ALL) cases. The remaining samples were submitted for RNA-seq. More than 96% of B-ALL cases and 74% of T-ALL cases could be identified based on the current molecular classification using this sequential approach. Patients with Philadelphia chromosome-like ALL constituted only 2.4% of the entire cohort, a rate even lower than those with ZNF384-rearranged (4.8%), DUX4-rearranged (6%), and Philadelphia chromosome-positive (4.4%) ALL. Patients with ETV6-RUNX1, high hyperdiploidy, PAX5 alteration, and DUX4 rearrangement had favorable prognosis, whereas those with hypodiploid and KMT2A and MEF2D rearrangement ALL had unfavorable outcomes. With the use of multiplex ligation-dependent probe amplification, DNA index, and RT-PCR in B-ALL and RT-PCR in T-ALL followed by RNA-seq, childhood ALL can be better classified to improve clinical assessments. CI - Copyright (c) 2022 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved. FAU - Yu, Chih-Hsiang AU - Yu CH AD - Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan. FAU - Wu, Gang AU - Wu G AD - Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee. FAU - Chang, Chia-Ching AU - Chang CC AD - Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan. FAU - Jou, Shiann-Tarng AU - Jou ST AD - Department of Pediatrics, National Taiwan University Children's Hospital, Taipei, Taiwan; Department of Pediatrics, College of Medicine, National Taiwan University, Taipei, Taiwan. FAU - Lu, Meng-Yao AU - Lu MY AD - Department of Pediatrics, National Taiwan University Children's Hospital, Taipei, Taiwan; Department of Pediatrics, College of Medicine, National Taiwan University, Taipei, Taiwan. FAU - Lin, Kai-Hsin AU - Lin KH AD - Department of Pediatrics, National Taiwan University Children's Hospital, Taipei, Taiwan. FAU - Chen, Shu-Huey AU - Chen SH AD - Department of Pediatrics, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan. FAU - Wu, Kang-Hsi AU - Wu KH AD - Department of Pediatrics, Chung Shan Medical University Hospital and School of Medicine, Chung Shan Medical University, Taichung, Taiwan. FAU - Huang, Fang-Liang AU - Huang FL AD - Department of Pediatrics, Taichung Veterans General Hospital, Taichung, Taiwan. FAU - Cheng, Chao-Neng AU - Cheng CN AD - Department of Pediatrics, National Cheng Kung University Hospital, Tainan, Taiwan. FAU - Chang, Hsiu-Hao AU - Chang HH AD - Department of Pediatrics, National Taiwan University Children's Hospital, Taipei, Taiwan; Department of Pediatrics, College of Medicine, National Taiwan University, Taipei, Taiwan. FAU - Hedges, Dale AU - Hedges D AD - Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee. FAU - Wang, Jinn-Li AU - Wang JL AD - Division of Hematology Oncology, Department of Pediatrics, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; Department of Pediatrics, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. FAU - Yen, Hsiu-Ju AU - Yen HJ AD - Department of Pediatrics, Taipei Veterans General Hospital and National Yang-Ming Chiao-Tung University School of Medicine, Taipei, Taiwan. FAU - Li, Meng-Ju AU - Li MJ AD - Department of Pediatrics, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu, Taiwan. FAU - Chou, Shu-Wei AU - Chou SW AD - Department of Pediatrics, National Taiwan University Children's Hospital, Taipei, Taiwan. FAU - Hung, Chen-Ting AU - Hung CT AD - Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan. FAU - Lin, Ze-Shiang AU - Lin ZS AD - Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan. FAU - Lin, Chien-Yu AU - Lin CY AD - Institute of Statistical Science Academia Sinica, Taipei, Taiwan. FAU - Chen, Hsuan-Yu AU - Chen HY AD - Institute of Statistical Science Academia Sinica, Taipei, Taiwan. FAU - Ni, Yu-Ling AU - Ni YL AD - Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan. FAU - Hsu, Yin-Chen AU - Hsu YC AD - Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan. FAU - Lin, Dong-Tsamn AU - Lin DT AD - Department of Pediatrics, National Taiwan University Children's Hospital, Taipei, Taiwan; Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan. FAU - Lin, Shu-Wha AU - Lin SW AD - Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan. FAU - Yang, Jun J AU - Yang JJ AD - Department of Pharmacology, St. Jude Children's Research Hospital, Memphis, Tennessee. FAU - Pui, Ching-Hon AU - Pui CH AD - Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee. FAU - Yu, Sung-Liang AU - Yu SL AD - Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan; Centers of Genomic and Precision Medicine, National Taiwan University, Taipei, Taiwan; Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan. Electronic address: slyu@ntu.edu.tw. FAU - Yang, Yung-Li AU - Yang YL AD - Department of Pediatrics, National Taiwan University Children's Hospital, Taipei, Taiwan; Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan; Department of Laboratory Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan. Electronic address: yangyl92@ntu.edu.tw. LA - eng GR - P30 CA021765/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20220810 PL - United States TA - J Mol Diagn JT - The Journal of molecular diagnostics : JMD JID - 100893612 RN - 0 (Oncogene Proteins, Fusion) RN - 9007-49-2 (DNA) SB - IM MH - Child MH - Humans MH - Oncogene Proteins, Fusion/genetics MH - *Precursor T-Cell Lymphoblastic Leukemia-Lymphoma MH - Philadelphia Chromosome MH - *Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis/genetics MH - Aneuploidy MH - DNA PMC - PMC9667711 EDAT- 2022/08/14 06:00 MHDA- 2022/11/08 06:00 PMCR- 2023/11/01 CRDT- 2022/08/13 19:36 PHST- 2022/03/15 00:00 [received] PHST- 2022/06/27 00:00 [revised] PHST- 2022/08/03 00:00 [accepted] PHST- 2022/08/14 06:00 [pubmed] PHST- 2022/11/08 06:00 [medline] PHST- 2022/08/13 19:36 [entrez] PHST- 2023/11/01 00:00 [pmc-release] AID - S1525-1578(22)00220-3 [pii] AID - 10.1016/j.jmoldx.2022.08.001 [doi] PST - ppublish SO - J Mol Diagn. 2022 Nov;24(11):1195-1206. doi: 10.1016/j.jmoldx.2022.08.001. Epub 2022 Aug 10.