Sequential Approach to Improve the Molecular Classification of Childhood Acute Lymphoblastic Leukemia

Chih Hsiang Yu, Gang Wu, Chia Ching Chang, Shiann Tarng Jou, Meng Yao Lu, Kai Hsin Lin, Shu Huey Chen, Kang Hsi Wu, Fang Liang Huang, Chao Neng Cheng, Hsiu Hao Chang, Dale Hedges, Jinn Li Wang, Hsiu Ju Yen, Meng Ju Li, Shu Wei Chou, Chen Ting Hung, Ze Shiang Lin, Chien Yu Lin, Hsuan Yu ChenYu Ling Ni, Yin Chen Hsu, Dong Tsamn Lin, Shu Wha Lin, Jun J. Yang, Ching Hon Pui, Sung Liang Yu, Yung Li Yang

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1195-1206
Number of pages12
JournalJournal of Molecular Diagnostics
Issue number11
Publication statusPublished - Nov 2022

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Medicine


Dive into the research topics of 'Sequential Approach to Improve the Molecular Classification of Childhood Acute Lymphoblastic Leukemia'. Together they form a unique fingerprint.

Cite this