The Role of miRNAs in Childhood Acute Lymphoblastic Leukemia Relapse and the Associated Molecular Mechanisms
Abstract
:1. Introduction
2. Acute Lymphoblastic Leukemia
3. Pediatric Acute Lymphoblastic Leukemia Therapy
4. Therapeutic Response
5. Mechanisms Underlying ALL Relapse
6. Strategies for Relapse Therapy
7. Side Effects of Pediatric Acute Lymphoblastic Leukemia Therapy
8. miRNAs Associated with Relapse in ALL
8.1. miR-24
8.2. miR-27a
8.3. miR-99 and miR-100
8.4. miR-124
8.5. miR-125b
8.6. miR-128b
8.7. miR-142-3p
8.8. miR-155
8.9. miR-335
9. Therapeutics and miRNAs Involved in ALL Relapse
10. Conclusions and Future Perspectives
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Standard Risk Factors | High Risk Factors | |
---|---|---|
Demographic and clinical features | ||
Age | 1 year to <10 year | <1 year or ≥10 years |
Sex | Female | Male |
Clinical, biological or genetic features of ALL | ||
Blood count at diagnosis | Blood count < 50 × 109 blood cells/mm3 per L for ALL-B and <100 × 109 blood cells/mm3 per L for T-cell ALL | count ≥ 50 × 109 blood cells/mm3 per L for B-ALL and ≥100 × 109 blood cells/mm3 per L for T-ALL |
Inmunophenotype | B-cell lineage | T-cell lineage |
Cytogenetics features | Hyperploidy, ETS variant 6 (ETV6)- Runt-related transcription factor (RUNX), transcription factor 3 (TCF3)-PBX homeobox 1 (PBX1), trisomy of chromosomes 4, 10 or 17 | Hypoploidy, Philadelphia chromosome positivity (breakpoint cluster region (BCR)-Abelson murine leukemia viral oncogene homolog 1 (ABL1)), MML TCF3-HLF rearrangement |
Genomic features | Double homeobox 4 (DUX4) rearrangement (ERG deletion) | IKAROS family zinc finger 1 (IKZF1) deletions, Philadelphia chromosome type, myocyte enhancer factor 2D (MEF2D) rearrangements |
Extramedullary disease | No | Yes |
Response to treatment | ||
minimal residual disease (MRD) | Low minimal residual disease < 103 nucleated cells or undetectable | Persistence of minimal residual disease ≥ 103 nucleated cells |
miRNA | Molecular Target | Drug resistance | Studies | Assay | Author |
---|---|---|---|---|---|
↓ miR-210 | E2F3, RAD52 | daunorubicine⁄dexametasone⁄ L-asparaginase/vincristine | Leukemia cells from patients with ALL Cell lines RS4;11 and REH | RT-qPCR | [93] |
↑ miR-223 | E2F1, E2A | Prednisolone | Leukemia cells from patients with ALL | Microarray | [14,15] |
↓ miR-326 | ABCA2 | Prednisone/methotrexate/ asparaginase/6-MP | Leukemia cells from patients with ALL | RT-qPCR | [94] |
↓ miR-652-3p | FOXK1 | Vincristine/cytarabine | Leukemia cells from patients with ALL; cell lines Reh and RS4:11 | Microarray | [3] |
↑ miR-708 | FOXO3 | MTX/6-PM/daunorubicine/ prednisone/VCR/ L-asparaginase | Leukemia cells from patients with ALL and cell line Jurkat | Microarray | [14] |
↑ miR-101–3p, ↑ miR-4774–5p, ↑ miR-1324, ↑ miR-631, ↑ miR-4699–5p, ↑ miR-922 | Cisplatine/ carboplatine/methotrexate | Leukemia cells from patients with ALL | Microarray | [95] |
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Barrios-Palacios, D.; Organista-Nava, J.; Balandrán, J.C.; Alarcón-Romero, L.d.C.; Zubillaga-Guerrero, M.I.; Illades-Aguiar, B.; Rivas-Alarcón, A.A.; Diaz-Lucas, J.J.; Gómez-Gómez, Y.; Leyva-Vázquez, M.A. The Role of miRNAs in Childhood Acute Lymphoblastic Leukemia Relapse and the Associated Molecular Mechanisms. Int. J. Mol. Sci. 2024, 25, 119. https://doi.org/10.3390/ijms25010119
Barrios-Palacios D, Organista-Nava J, Balandrán JC, Alarcón-Romero LdC, Zubillaga-Guerrero MI, Illades-Aguiar B, Rivas-Alarcón AA, Diaz-Lucas JJ, Gómez-Gómez Y, Leyva-Vázquez MA. The Role of miRNAs in Childhood Acute Lymphoblastic Leukemia Relapse and the Associated Molecular Mechanisms. International Journal of Molecular Sciences. 2024; 25(1):119. https://doi.org/10.3390/ijms25010119
Chicago/Turabian StyleBarrios-Palacios, Dalia, Jorge Organista-Nava, Juan Carlos Balandrán, Luz del Carmen Alarcón-Romero, Ma Isabel Zubillaga-Guerrero, Berenice Illades-Aguiar, Alinne Ayulieth Rivas-Alarcón, Jessica Julieth Diaz-Lucas, Yazmín Gómez-Gómez, and Marco Antonio Leyva-Vázquez. 2024. "The Role of miRNAs in Childhood Acute Lymphoblastic Leukemia Relapse and the Associated Molecular Mechanisms" International Journal of Molecular Sciences 25, no. 1: 119. https://doi.org/10.3390/ijms25010119