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Review
. 2024 Jun 4:15:1394523.
doi: 10.3389/fgene.2024.1394523. eCollection 2024.

Advances in next-generation sequencing for relapsed pediatric acute lymphoblastic leukemia: current insights and future directions

Nur Farhana Mohd Nippah  1 , Nadiah Abu  2 , Nurul Syakima Ab Mutalib  2 , Hamidah Alias  1   2
Affiliations
Review

Advances in next-generation sequencing for relapsed pediatric acute lymphoblastic leukemia: current insights and future directions

Nur Farhana Mohd Nippah et al. Front Genet. .

Abstract

Leukemia is one of the most common cancers in children; and its genetic diversity in the landscape of acute lymphoblastic leukemia (ALL) is important for diagnosis, risk assessment, and therapeutic approaches. Relapsed ALL remains the leading cause of cancer deaths among children. Almost 20% of children who are treated for ALL and achieve complete remission experience disease recurrence. Relapsed ALL has a poor prognosis, and relapses are more likely to have mutations that affect signaling pathways, chromatin patterning, tumor suppression, and nucleoside metabolism. The identification of ALL subtypes has been based on genomic alterations for several decades, using the molecular landscape at relapse and its clinical significance. Next-generation sequencing (NGS), also known as massive parallel sequencing, is a high-throughput, quick, accurate, and sensitive method to examine the molecular landscape of cancer. This has undoubtedly transformed the study of relapsed ALL. The implementation of NGS has improved ALL genomic analysis, resulting in the recent identification of various novel molecular entities and a deeper understanding of existing ones. Thus, this review aimed to consolidate and critically evaluate the most current information on relapsed pediatric ALL provided by NGS technology. In this phase of targeted therapy and personalized medicine, identifying the capabilities, benefits, and drawbacks of NGS will be essential for healthcare professionals and researchers offering genome-driven care. This would contribute to precision medicine to treat these patients and help improve their overall survival and quality of life.

Keywords: cancer genome; molecular landscape; next-generation sequencing; precision medicine; relapsed acute lymphoblastic leukemia.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

FIGURE 1
FIGURE 1
Recurrently mutated genes and pathways in ALL and the various roles of genes that are significantly mutated in ALL. The genes were discovered during relapse and caused treatment resistance. Red asterisks denote the genes that cause the ALL to be resistant to treatment, thus causing relapse.
See this image and copyright information in PMC

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References

    1. Antic Ž., Lelieveld S. H., Van Der Ham C. G., Sonneveld E., Hoogerbrugge P. M., Kuiper R. P. (2021). Unravelling the sequential interplay of mutational mechanisms during clonal evolution in relapsed pediatric acute lymphoblastic leukemia. Genes (Basel) 12 (2), 214. 10.3390/genes12020214 - DOI - PMC - PubMed
    1. Antić Ž., Yu J., Bornhauser B. C., Lelieveld S. H., van der Ham C. G., van Reijmersdal S. V., et al. (2022). Clonal dynamics in pediatric B-cell precursor acute lymphoblastic leukemia with very early relapse. Pediatr. Blood Cancer 69 (1), e29361. 10.1002/pbc.29361 - DOI - PubMed
    1. Antonarakis S. E., Krawczak M., Cooper D. N. (1995) The nature and mechanisms of human gene mutation. The online metabolic and molecular bases of inherited disease.
    1. Atha B. B. (2023) When to use whole-genome vs. Whole-exome sequencing.
    1. Bertier G., Hétu M., Joly Y. (2016). Unsolved challenges of clinical whole-exome sequencing: a systematic literature review of end-users' views. BMC Med. Genomics 9 (1), 52. 10.1186/s12920-016-0213-6 - DOI - PMC - PubMed

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