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Page 391 Santiago et al. J Transl Genet Genom 2021;5:380-95 https://dx.doi.org/10.20517/jtgg.2021.16

CONCLUSION
Advances of high-throughput sequencing technologies redefine the genomic portrait of ALL and modernize
ALL classification, with only a marginal proportion of patients remaining unclassified in the current
molecular landscape. Beside Ph and Ph-like ALL for whom robust preclinical and clinical evidence
+
supports the prospective assessment of TKI and chemotherapy in frontline trials, a substantial proportion of
molecular subsets, particularly those associated with unfavorable outcomes, still lacks access to key
therapeutic targets and relevant precision medicine trials. Continuous efforts in elucidating the functional
mechanisms underlying the subtype-defining alterations in ALL is essential to expand the spectrum of novel
targeted therapies. Nevertheless, the development of new therapeutic options and consequently the design
of clinical trials are hindered by the growing number of molecular subsets, each accounting for a small
proportion of ALL. Large international clinical trials are therefore critical to explore innovative treatments
combining chemo-, immuno- and targeted therapies, with the objectives of improving survival in HR
subtypes and reducing toxicity in low-risk ALL. The current molecular era of ALL present unique
challenges but also offers exciting opportunities for paradigm-shifting therapies.

DECLARATIONS
Authors’ contributions
Performed the literature review and wrote the manuscript: Santiago R, Tran TH
Both authors contributed equally to this work.

Availability of data and materials
Not applicable.

Financial support and sponsorship
None.

Conflicts of interest
Both authors declared that there are no conflicts of interest.

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

Copyright
© The Author(s) 2021.

REFERENCES
1. Hunger SP, Lu X, Devidas M, et al. Improved survival for children and adolescents with acute lymphoblastic leukemia between 1990
and 2005: a report from the children's oncology group. J Clin Oncol 2012;30:1663-9. DOI PubMed PMC
2. Pui CH, Yang JJ, Hunger SP, et al. childhood acute lymphoblastic leukemia: progress through collaboration. J Clin Oncol
2015;33:2938-48. DOI PubMed PMC
3. Santiago R, Vairy S, Sinnett D, Krajinovic M, Bittencourt H. Novel therapy for childhood acute lymphoblastic leukemia. Expert Opin
Pharmacother 2017;18:1081-99. DOI PubMed
4. Smith M, Arthur D, Camitta B, et al. Uniform approach to risk classification and treatment assignment for children with acute
lymphoblastic leukemia. J Clin Oncol 1996;14:18-24. DOI PubMed
5. Harrison CJ, Moorman AV, Schwab C, Iacobucci I, Mullighan C. Cytogenetics and molecular genetics. In: Vora A, editor. Childhood
acute lymphoblastic leukemia. Cham: Springer International Publishing; 2017. p. 61-98.
6. Schultz KR, Pullen DJ, Sather HN, et al. Risk- and response-based classification of childhood B-precursor acute lymphoblastic
leukemia: a combined analysis of prognostic markers from the Pediatric Oncology Group (POG) and Children's Cancer Group
(CCG). Blood 2007;109:926-35. DOI PubMed PMC