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Santiago et al. J Transl Genet Genom 2021;5:380-95 Journal of Translational
DOI: 10.20517/jtgg.2021.16
Genetics and Genomics

Review Open Access

Genomics and precision medicine in pediatric acute
lymphoblastic leukemia

1,2
Raoul Santiago , Thai Hoa Tran 3,4
1
Division of Pediatric Hematology-Oncology, Centre Hospitalier Universitaire de l’Université Laval, Charles Bruneau Cancer
Center, Quebec, QC G1V 4G2, Canada.
2
CHU de Québec Research Center, Université Laval, Quebec, QC G1V 4G2, Canada.
3
Division of Pediatric Hematology-Oncology, Centre Hospitalier Universitaire Sainte Justine, Charles-Bruneau Cancer Center,
Montreal, QC H3T 1C5, Canada.
4
CHU Sainte-Justine Research Center, Université de Montreal, Montreal, QC H3T 1C5, Canada.
Correspondence to: Thai Hoa Tran, MD, CHU Sainte-Justine Research Center, Université de Montreal, 3175 Chemin Cote
Sainte-Catherine, Local A-435, Montreal, QC H3T 1C5 Canada. E-mail: thai.hoa.tran@umontreal.ca
How to cite this article: Santiago R, Tran TH. Genomics and precision medicine in pediatric acute lymphoblastic leukemia. J
Transl Genet Genom 2021;5:380-95. https://dx.doi.org/10.20517/jtgg.2021.16
Received: 16 Mar 2021 Accepted: 11 Jun 2021 Published: 19 Oct 2021

Academic Editors: Susan L. Slager, Sanjay Gupta Copy Editor: Xi-Jun Chen Production Editor: Xi-Jun Chen

Abstract
Acute lymphoblastic leukemia (ALL) is the most frequent malignant disease in the pediatric population, accounting
for about 25% of childhood cancers. Drastic therapeutic improvements have been made for pediatric ALL since the
early 1960s, marking the most successful treatment paradigm in pediatric oncology. The clinical success derived
from refined risk-adapted therapy based on presenting features, cytogenetics and minimal residual disease,
prevention of central nervous system relapse, and improvement of supportive care measures. With contemporary
therapies, survival of children with ALL now exceeds 90%. However, ALL represents one of leading causes of
cancer-related death, as 15%-20% of patients continue to relapse and outcomes post-relapse remain poor. Since
the early 2000s, large-scale genomic studies of ALL, greatly facilitated by the advent of next generation
sequencing (NGS), have enabled the development of a novel taxonomy for ALL in the molecular era. The access to
NGS technologies identifies novel ALL subsets characterized by “driver” oncogenic alterations, previously cryptic
on conventional karyotyping methods. With genomic characterization, the group of formerly unclassified B-lineage
ALL reduces from 25% to a marginal 5% of ALL. The revised molecular classification of ALL confers prognostic
significance and describes the predilection of unfavorable ALL subtypes with increasing age, partially elucidating
the worst outcome of adolescents and young adults with ALL. Large-scale genomic analysis also reveals inherited
alterations predisposing to ALL occurrence or to different drugs’ sensitivities. Most importantly, the genomic
portrait of ALL uncovers novel therapeutic vulnerabilities, paving the way towards precision medicine opportunities

© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing,
adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as
long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and
indicate if changes were made.

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