{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T23:00:59Z","timestamp":1793314859020,"version":"4.5.0"},"reference-count":121,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T00:00:00Z","timestamp":1745539200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Universidade de Bras\u00edlia, Fundac\u00e3o de Amparo \u00e0 Pesquisa do Distrito Federal (FAPDF)"},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (CNPq)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Liquid biopsy is classically defined as the detection of biomarkers in bodily fluids. One of these biomarkers can be circulating cell-free DNA (cfDNA) released by healthy or cancer cells during apoptosis. These fragments can be quantified and molecularly characterized by techniques like digital droplet PCR (ddPCR) or next-generation sequencing (NGS). By identifying common genetic and epigenetic alterations associated with specific cancer types, cfDNA or circulating tumor DNA (ctDNA) can serve as robust biomarkers for monitoring tumor initiation and progression. Other biomarkers, such as circulating microRNAs (miRNAs), extracellular vesicles, or circulating tumor cells (CTCs) are also applied in this context. Liquid biopsy has gained attention as a versatile tool for cancer diagnostics, prognosis, therapeutic monitoring, and minimal residual disease (MRD) detection across various malignancies, including hematological cancers like myeloid and lymphoid leukemias. Herein, we present a comprehensive review of liquid biopsy usage in leukemia, with a specific focus on the clinical utility of ctDNA, miRNAs, and exosomes in monitoring treatment response, tracking clonal evolution, and detecting minimal residual disease. Our review emphasizes the translational implications of these tools for improving patient outcomes and outlines current challenges in their integration into clinical practice.<\/jats:p>","DOI":"10.3390\/cancers17091438","type":"journal-article","created":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T06:10:13Z","timestamp":1745561413000},"page":"1438","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Advancing Leukemia Management Through Liquid Biopsy: Insights into Biomarkers and Clinical Utility"],"prefix":"10.3390","volume":"17","author":[{"given":"C\u00edntia Nogueira","family":"Hollanda","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Pathology of Cancer, Faculty of Health Sciences, University of Brasilia, Brasilia 70910-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Cristina Moura","family":"Gualberto","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pathology of Cancer, Faculty of Health Sciences, University of Brasilia, Brasilia 70910-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9280-2638","authenticated-orcid":false,"given":"Andr\u00e9a Barretto","family":"Motoyama","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pathology of Cancer, Faculty of Health Sciences, University of Brasilia, Brasilia 70910-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9644-7098","authenticated-orcid":false,"given":"Fabio","family":"Pittella-Silva","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pathology of Cancer, Faculty of Health Sciences, University of Brasilia, Brasilia 70910-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e577","DOI":"10.1038\/bcj.2017.53","article-title":"Acute lymphoblastic leukemia: A comprehensive review and 2017 update","volume":"7","author":"Terwilliger","year":"2017","journal-title":"Blood Cancer J."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Teixeira, A., Carreira, L., Abalde-Cela, S., Sampaio-Marques, B., Areias, A.C., Ludovico, P., and Di\u00e9guez, L. (2023). Current and Emerging Techniques for Diagnosis and MRD Detection in AML: A Comprehensive Narrative Review. Cancers, 15.","DOI":"10.3390\/cancers15051362"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Combaluzier, S., Quessada, J., Abbou, N., Arcani, R., Tichadou, A., Gabert, J., Costello, R., Loosveld, M., Venton, G., and Berda-Haddad, Y. (2023). Cytological Diagnosis of Classic Myeloproliferative Neoplasms at the Age of Molecular Biology. Cells, 12.","DOI":"10.3390\/cells12060946"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"P\u00e9rez-Carretero, C., Gonz\u00e1lez-Gasc\u00f3n-Y-Mar\u00edn, I., Rodr\u00edguez-Vicente, A.E., Quijada-\u00c1lamo, M., Hern\u00e1ndez-Rivas, J., Hern\u00e1ndez-S\u00e1nchez, M., and Hern\u00e1ndez-Rivas, J.M. (2021). The Evolving Landscape of Chronic Lymphocytic Leukemia on Diagnosis, Prognosis and Treatment. Diagnostics, 11.","DOI":"10.3390\/diagnostics11050853"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Savino, F.D., Rigali, F., Giustini, V., D\u2019aliberti, D., Spinelli, S., Piazza, R., Sacco, A., and Roccaro, A.M. (2022). Liquid Biopsy in Cancer: Focus on Lymphoproliferative Disorders. Cancers, 14.","DOI":"10.3390\/cancers14215378"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1038\/nrclinonc.2013.110","article-title":"Liquid biopsy: Monitoring cancer-genetics in the blood","volume":"10","author":"Crowley","year":"2013","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"102","DOI":"10.37349\/etat.2023.00125","article-title":"Diagnostic value of liquid biopsy in the era of precision medicine: 10 years of clinical evidence in cancer","volume":"4","author":"Caputo","year":"2023","journal-title":"Explor. Target. Anti-Tumor Ther."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Kurniali, P.C., Storandt, M.H., and Jin, Z. (2023). Utilization of Circulating Tumor Cells in the Management of Solid Tumors. J. Pers. Med., 13.","DOI":"10.3390\/jpm13040694"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Birk\u00f3, Z., Nagy, B., Klekner, \u00c1., and Virga, J. (2020). Novel Molecular Markers in Glioblastoma\u2014Benefits of Liquid Biopsy. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21207522"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s12943-022-01710-w","article-title":"Circulating tumor nucleic acids: Biology, release mechanisms, and clinical relevance","volume":"22","author":"Stejskal","year":"2023","journal-title":"Mol. Cancer"},{"key":"ref_11","first-page":"117","article-title":"The power of microRNAs as diagnostic and prognostic biomarkers in liquid biopsies","volume":"3","author":"Quirico","year":"2020","journal-title":"Cancer Drug Resist."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.ncrna.2020.02.001","article-title":"Overview of current microRNA biomarker signatures as potential diagnostic tools for leukaemic conditions","volume":"5","author":"Buhagiar","year":"2020","journal-title":"Non-Coding RNA Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"15330338211011958","DOI":"10.1177\/15330338211011958","article-title":"The Potential Diagnostic Accuracy of Circulating MicroRNAs for Leukemia: A Meta-Analysis","volume":"20","author":"Zhang","year":"2021","journal-title":"Technol. Cancer Res. Treat."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1535750","DOI":"10.1080\/20013078.2018.1535750","article-title":"Minimal information for studies of extracellular vesicles 2018 (MISEV2018): A position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines","volume":"7","author":"Witwer","year":"2018","journal-title":"J. Extracell. Vesicles"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1016\/j.annonc.2021.01.074","article-title":"Exosome-based liquid biopsies in cancer: Opportunities and challenges","volume":"32","author":"Yu","year":"2021","journal-title":"Ann. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1038\/s41375-020-01104-1","article-title":"Clinical relevance of extracellular vesicles in hematological neoplasms: From liquid biopsy to cell biopsy","volume":"35","author":"Trino","year":"2021","journal-title":"Leukemia"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Wang, W., Rong, Z., Wang, G., Hou, Y., Yang, F., and Qiu, M. (2023). Cancer metabolites: Promising biomarkers for cancer liquid biopsy. Biomark. Res., 11.","DOI":"10.1186\/s40364-023-00507-3"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1007\/s00432-022-04113-y","article-title":"Circulating metabolite biomarkers: A game changer in the human prostate cancer diagnosis","volume":"149","author":"Krishnan","year":"2022","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s13402-018-0413-5","article-title":"Cell-free DNA in cancer: Current insights","volume":"42","author":"Fettke","year":"2018","journal-title":"Cell. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.cell.2015.11.050","article-title":"Cell-free DNA Comprises an In Vivo Nucleosome Footprint that Informs Its Tissues-Of-Origin","volume":"164","author":"Snyder","year":"2016","journal-title":"Cell"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.bbcan.2006.10.001","article-title":"Circulating nucleic acids (CNAs) and cancer\u2014A survey","volume":"1775","author":"Fleischhacker","year":"2007","journal-title":"Biochim. Biophys. Acta (BBA)-Rev. Cancer"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1038\/s41571-019-0187-3","article-title":"Liquid biopsy and minimal residual disease\u2014Latest advances and implications for cure","volume":"16","author":"Pantel","year":"2019","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"iv192","DOI":"10.1093\/annonc\/mdy275","article-title":"Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"29","author":"Planchard","year":"2018","journal-title":"Ann Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Kemper, M., Krekeler, C., Menck, K., Lenz, G., Evers, G., Schulze, A.B., and Bleckmann, A. (2023). Liquid Biopsies in Lung Cancer. Cancers, 15.","DOI":"10.3390\/cancers15051430"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1007\/s40291-017-0259-y","article-title":"Epi proColon\u00ae 2.0 CE: A Blood-Based Screening Test for Colorectal Cancer","volume":"21","author":"Lamb","year":"2017","journal-title":"Mol. Diagn. Ther."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"de Abreu, A.R., de Beeck, K.O., Laurent-Puig, P., Taly, V., and Benhaim, L. (2023). The Position of Circulating Tumor DNA in the Clinical Management of Colorectal Cancer. Cancers, 15.","DOI":"10.3390\/cancers15041284"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"de Freitas, A.J.A., Causin, R.L., Varuzza, M.B., Calfa, S., Filho, C.M.T.H., Komoto, T.T., Souza, C.d.P., and Marques, M.M.C. (2022). Liquid Biopsy as a Tool for the Diagnosis, Treatment, and Monitoring of Breast Cancer. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23179952"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1001\/jamaoncol.2020.2295","article-title":"Association of Circulating Tumor DNA and Circulating Tumor Cells After Neoadjuvant Chemotherapy with Disease Recurrence in Patients with Triple-Negative Breast Cancer: Preplanned Secondary Analysis of the BRE12-158 Randomized Clinical Trial","volume":"6","author":"Radovich","year":"2020","journal-title":"JAMA Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Davis, A.A., Jacob, S., Gerratana, L., Shah, A.N., Wehbe, F., Katam, N., Zhang, Q., Flaum, L., Siziopikou, K.P., and Platanias, L.C. (2020). Landscape of circulating tumour DNA in metastatic breast cancer. eBioMedicine, 58.","DOI":"10.1016\/j.ebiom.2020.102914"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Ogawa, M., Yokoyama, K., Imoto, S., and Tojo, A. (2021). Role of Circulating Tumor DNA in Hematological Malignancy. Cancers, 13.","DOI":"10.3390\/cancers13092078"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1515\/cclm-2021-1152","article-title":"Circulating cell-free DNA undergoes significant decline in yield after prolonged storage time in both plasma and purified form","volume":"60","author":"Yuwono","year":"2022","journal-title":"Clin. Chem. Lab. Med. (CCLM)"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.cancergen.2018.08.005","article-title":"Evaluation of commercial kits for purification of circulating free DNA","volume":"228\u2013229","author":"Diefenbach","year":"2018","journal-title":"Cancer Genet."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1758835918794630","DOI":"10.1177\/1758835918794630","article-title":"Liquid biopsy of cancer: A multimodal diagnostic tool in clinical oncology","volume":"10","author":"Palmirotta","year":"2018","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"102978","DOI":"10.1016\/j.critrevonc.2020.102978","article-title":"Challenges and opportunities of cfDNA analysis implementation in clinical practice: Perspective of the International Society of Liquid Biopsy (ISLB)","volume":"151","author":"Rolfo","year":"2020","journal-title":"Crit. Rev. Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1373\/clinchem.2013.214874","article-title":"Rapid Electrokinetic Isolation of Cancer-Related Circulating Cell-Free DNA Directly from Blood","volume":"60","author":"Sonnenberg","year":"2014","journal-title":"Clin. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1002\/hon.3087","article-title":"Circulating cell-free DNA for target quantification in hematologic malignancies: Validation of a protocol to overcome pre-analytical biases","volume":"41","author":"Soscia","year":"2022","journal-title":"Hematol. Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1016\/j.jmoldx.2021.08.008","article-title":"PCR-Free Shallow Whole Genome Sequencing for Chromosomal Copy Number Detection from Plasma of Cancer Patients Is an Efficient Alternative to the Conventional PCR-Based Approach","volume":"23","author":"Beagan","year":"2021","journal-title":"J. Mol. Diagn."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Sampathi, S., Chernyavskaya, Y., Haney, M.G., Moore, L.H., Snyder, I.A., Cox, A.H., Fuller, B.L., Taylor, T.J., Yan, D., and Badgett, T.C. (2022). Nanopore sequencing of clonal IGH rearrangements in cell-free DNA as a biomarker for acute lymphoblastic leukemia. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.958673"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e87","DOI":"10.1093\/nar\/gkz474","article-title":"High efficiency error suppression for accurate detection of low-frequency variants","volume":"47","author":"Wang","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/s12943-016-0536-0","article-title":"Clinical relevance of circulating cell-free microRNAs in ovarian cancer","volume":"15","author":"Nakamura","year":"2016","journal-title":"Mol. Cancer"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Pozniak, T., Shcharbin, D., and Bryszewska, M. (2022). Circulating microRNAs in Medicine. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23073996"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"6618","DOI":"10.1021\/acs.analchem.8b00405","article-title":"Analysis of Circulating microRNAs and Their Post-Transcriptional Modifications in Cancer Serum by On-Line Solid-Phase Extraction\u2013Capillary Electrophoresis\u2013Mass Spectrometry","volume":"90","author":"Berezovski","year":"2018","journal-title":"Anal. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"16271","DOI":"10.1039\/C5CC06549F","article-title":"A new enzyme-free quadratic SERS signal amplification approach for circulating microRNA detection in human serum","volume":"51","author":"Zheng","year":"2015","journal-title":"Chem. Commun."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"123444","DOI":"10.1016\/j.talanta.2022.123444","article-title":"Rolling circle amplification assisted dual signal amplification colorimetric biosensor for ultrasensitive detection of leukemia-derived exosomes","volume":"245","author":"Li","year":"2022","journal-title":"Talanta"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.1039\/D0AN02257H","article-title":"Facile PEG-based isolation and classification of cancer extracellular vesicles and particles with label-free surface-enhanced Raman scattering and pattern recognition algorithm","volume":"146","author":"Yin","year":"2021","journal-title":"Analyst"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1039\/D0AN01420F","article-title":"Isolation of extracellular vesicles with multivalent aptamers","volume":"146","author":"Xue","year":"2020","journal-title":"Analyst"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1007\/s10528-018-9844-y","article-title":"Aberrant Expression of Some Circulating miRNAs in Childhood Acute Lymphoblastic Leukemia","volume":"56","author":"Swellam","year":"2018","journal-title":"Biochem. Genet."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Shahid, S., Shahid, W., Shaheen, J., Akhtar, M.W., and Sadaf, S. (2021). Circulating miR-146a expression as a non-invasive predictive biomarker for acute lymphoblastic leukemia. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-02257-4"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"299","DOI":"10.3233\/CBM-150465","article-title":"Circulating microRNA expression profile in B-cell acute lymphoblastic leukemia","volume":"15","year":"2015","journal-title":"Cancer Biomark."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"George, N.G., Rishi, B., Singh, A., Vishmaya, S., Kumar, R., Kushwaha, N., Kaur, M., Bhardwaj, R., Jain, A., and Jain, A. (2024). Early prognosis prediction in acute myeloid and acute lymphoid leukemia patients using cell-free DNA concentration ratios. Front. Mol. Biosci., 10.","DOI":"10.3389\/fmolb.2023.1333943"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1182\/bloodadvances.2017008680","article-title":"Maternal iAMP21 acute lymphoblastic leukemia detected on prenatal cell-free DNA genetic screening","volume":"1","author":"Luskin","year":"2017","journal-title":"Blood Adv."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2688","DOI":"10.1039\/C8LC01370E","article-title":"Intelligent whole-blood imaging flow cytometry for simple, rapid, and cost-effective drug-susceptibility testing of leukemia","volume":"19","author":"Kobayashi","year":"2019","journal-title":"Lab A Chip"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1002\/jha2.510","article-title":"CB-103: A novel CSL-NICD inhibitor for the treatment of NOTCH-driven T-cell acute lymphoblastic leukemia: A case report of complete clinical response in a patient with relapsed and refractory T-ALL","volume":"3","author":"Medinger","year":"2022","journal-title":"eJHaem"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Aljurf, M., Abalkhail, H., Alseraihy, A., Mohamed, S.Y., Ayas, M., Alsharif, F., Alzahrani, H., Al-Jefri, A., Aldawsari, G., and Al-Ahmari, A. (2016). Chimerism Analysis of Cell-Free DNA in Patients Treated with Hematopoietic Stem Cell Transplantation May Predict Early Relapse in Patients with Hematologic Malignancies. Biotechnol. Res. Int., 2016.","DOI":"10.1155\/2016\/8589270"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Arthur, C., Rezayee, F., Mogensen, N., Saft, L., Rosenquist, R., Nordenskj\u00f6ld, M., Harila-Saari, A., Tham, E., and Barbany, G. (2022). Patient-Specific Assays Based on Whole-Genome Sequencing Data to Measure Residual Disease in Children With Acute Lymphoblastic Leukemia: A Proof of Concept Study. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.899325"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1038\/s41375-024-02461-x","article-title":"Genomic profiling of circulating tumor DNA for childhood cancers","volume":"39","author":"Lei","year":"2024","journal-title":"Leukemia"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"6524","DOI":"10.1200\/JCO.2024.42.16_suppl.6524","article-title":"Molecular characterization and biomarker identification in pediatric B-cell acute lymphoblastic leukemia","volume":"42","author":"Du","year":"2024","journal-title":"J. Clin. Oncol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1186\/s12967-019-2114-x","article-title":"Circulating microRNAs as minimal residual disease biomarkers in childhood acute lymphoblastic leukemia","volume":"17","author":"Rzepiel","year":"2019","journal-title":"J. Transl. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"101893","DOI":"10.1016\/j.mcp.2023.101893","article-title":"MiR-128-3p as blood based liquid biopsy biomarker in childhood acute lymphoblastic leukemia","volume":"67","author":"Rzepiel","year":"2023","journal-title":"Mol. Cell. Probes"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1610096","DOI":"10.3389\/pore.2022.1610096","article-title":"Co-Detection of VEGF-A and Its Regulator, microRNA-181a, May Indicate Central Nervous System Involvement in Pediatric Leukemia","volume":"28","author":"Egyed","year":"2022","journal-title":"Pathol. Oncol. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1186\/s12967-020-02415-8","article-title":"MicroRNA-181a as novel liquid biopsy marker of central nervous system involvement in pediatric acute lymphoblastic leukemia","volume":"18","author":"Egyed","year":"2020","journal-title":"J. Transl. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1186\/s10020-022-00588-0","article-title":"MicroRNA composition of plasma extracellular vesicles: A harbinger of late cardiotoxicity of doxorubicin","volume":"28","author":"Seweryn","year":"2022","journal-title":"Mol. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e12557","DOI":"10.1002\/rth2.12557","article-title":"Thrombotic potential during pediatric acute lymphoblastic leukemia induction: Role of cell-free DNA","volume":"5","author":"Kumar","year":"2021","journal-title":"Res. Pract. Thromb. Haemost."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1093\/annonc\/mdy476","article-title":"Genomewide copy number alteration screening of circulating plasma DNA: Potential for the detection of incipient tumors","volume":"30","author":"Lenaerts","year":"2019","journal-title":"Ann. Oncol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1002\/ijc.32894","article-title":"Serum levels of hsa-miR-16-5p, hsa-miR-29a-3p, hsa-miR-150-5p, hsa-miR-155-5p and hsa-miR-223-3p and subsequent risk of chronic lymphocytic leukemia in the EPIC study","volume":"147","author":"Casabonne","year":"2020","journal-title":"Int. J. Cancer"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1159\/000521841","article-title":"Clinical Utility of Liquid Biopsy to Identify Genomic Heterogeneity and Secondary Cancer Diagnoses: A Case Report","volume":"15","author":"Hemenway","year":"2022","journal-title":"Case Rep. Oncol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1002\/pd.6158","article-title":"Discordant cfDNA-NIPT result unraveling a trisomy 12 chronic lymphocytic leukemia in a 37 years old pregnant woman","volume":"42","author":"Bottillo","year":"2022","journal-title":"Prenat. Diagn."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"14756","DOI":"10.1038\/ncomms14756","article-title":"Circulating tumour DNA reflects treatment response and clonal evolution in chronic lymphocytic leukaemia","volume":"8","author":"Yeh","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"17936","DOI":"10.18632\/oncotarget.15316","article-title":"Using high-sensitivity sequencing for the detection of mutations in BTK and PLC\u03b32 genes in cellular and cell-free DNA and correlation with progression in patients treated with BTK inhibitors","volume":"8","author":"Albitar","year":"2017","journal-title":"Oncotarget"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1016\/j.cell.2019.06.011","article-title":"Dynamic risk profiling using serial tumor biomarkers for personalized outcome Prediction","volume":"178","author":"Kurtz","year":"2019","journal-title":"Cell"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"123","DOI":"10.2119\/molmed.2014.00214","article-title":"Opposite Prognostic Significance of Cellular and Serum Circulating MicroRNA-150 in Patients with Chronic Lymphocytic Leukemia","volume":"21","author":"Stamatopoulos","year":"2015","journal-title":"Mol. Med."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Shao, J., Wang, S., West-Szymanski, D., Karpus, J., Shah, S., Ganguly, S., Smith, J., Zu, Y., He, C., and Li, Z. (2022). Cell-free DNA 5-hydroxymethylcytosine is an emerging marker of acute myeloid leukemia. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-16685-3"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Xiao, Q., Lin, C., Peng, M., Ren, J., Jing, Y., Lei, L., Tao, Y., Huang, J., Yang, J., and Sun, M. (2022). Circulating plasma exosomal long non-coding RNAs LINC00265, LINC00467, UCA1, and SNHG1 as biomarkers for diagnosis and treatment monitoring of acute myeloid leukemia. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.1033143"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Ruan, M., Liu, L., Qi, B., Chen, X., Chang, L., Zhang, A., Guo, Y., Zou, Y., Zhang, Y., and Chen, Y. (2021). Targeted Next-Generation Sequencing of Circulating Tumor DNA, Bone Marrow, and Peripheral Blood Mononuclear Cells in Pediatric AML. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.666470"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Shao, J., Shah, S., Ganguly, S., Zu, Y., He, C., and Li, Z. (2023). Classification of Acute Myeloid Leukemia by Cell-Free DNA 5-Hydroxymethylcytosine. Genes, 14.","DOI":"10.3390\/genes14061180"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2241","DOI":"10.1007\/s00277-021-04579-9","article-title":"Acute promyelocytic leukemia derived extracellular vesicles conserve PML-RAR\u03b1 transcript from storage-inflicted degradation: A stable diagnosis tool in APL patients","volume":"100","author":"Barzegar","year":"2021","journal-title":"Ann. Hematol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"a006201","DOI":"10.1101\/mcs.a006201","article-title":"Incidental discovery of acute myeloid leukemia during liquid biopsy of a lung cancer patient","volume":"8","author":"Nkosi","year":"2022","journal-title":"Cold Spring Harb. Mol. Case Stud."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Kerle, I.A., J\u00e4gerhuber, L., Secci, R., Pfarr, N., Bl\u00fcm, P., Roesch, R., G\u00f6tze, K.S., Weichert, W., Bassermann, F., and Ruland, J. (2022). Circulating Tumor DNA Profiling of a Diffuse Large B Cell Lymphoma Patient with Secondary Acute Myeloid Leukemia. Cancers, 14.","DOI":"10.3390\/cancers14061371"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1016\/j.leukres.2015.08.009","article-title":"The impact of standard chemotherapy on miRNA signature in plasma in AML patients","volume":"39","author":"Koutova","year":"2015","journal-title":"Leuk. Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"6132","DOI":"10.1158\/1078-0432.CCR-20-2586","article-title":"A Phase Ib Study of Onvansertib, a Novel Oral PLK1 Inhibitor, in Combination Therapy for Patients with Relapsed or Refractory Acute Myeloid Leukemia","volume":"26","author":"Zeidan","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"e1349","DOI":"10.1002\/ctm2.1349","article-title":"Serial monitoring of circulating tumour DNA on clinical outcome in myelodysplastic syndromes and acute myeloid leukaemia","volume":"13","author":"Zhou","year":"2023","journal-title":"Clin. Transl. Med."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1016\/j.ijrobp.2021.10.150","article-title":"Utility of Circulating MicroRNA-150 for Rapid Evaluation of Bone Marrow Depletion After Radiation and Efficiency of Bone Marrow Reconstitution","volume":"112","author":"Yadav","year":"2022","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1515\/CCLM.2010.311","article-title":"Increased integrity of circulating cell-free DNA in plasma of patients with acute leukemia","volume":"48","author":"Gao","year":"2010","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_84","first-page":"2279","article-title":"Monitoring immunoglobulin heavy chain and T-cell receptor gene rearrangement in cfDNA as minimal residual disease detection for patients with acute myeloid leukemia","volume":"16","author":"Zhong","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.1182\/bloodadvances.2019001156","article-title":"Targeted next-generation sequencing of circulating cell-free DNA vs bone marrow in patients with acute myeloid leukemia","volume":"4","author":"Short","year":"2020","journal-title":"Blood Adv."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1016\/j.jmoldx.2021.05.001","article-title":"Double Drop-Off Droplet Digital PCR: A Novel, Versatile Tool for Mutation Screening and Residual Disease Monitoring in Acute Myeloid Leukemia Using Cellular or Cell-Free DNA","volume":"23","author":"Rausch","year":"2021","journal-title":"J. Mol. Diagn."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1200\/JCO.19.03011","article-title":"Impact of Conditioning Intensity of Allogeneic Transplantation for Acute Myeloid Leukemia With Genomic Evidence of Residual Disease","volume":"38","author":"Hourigan","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1111\/his.15168","article-title":"Liquid biopsy-based circulating tumor (ct)DNA analysis of a spectrum of myeloid and lymphoid malignancies yields clinically actionable results","volume":"84","author":"Mata","year":"2024","journal-title":"Histopathology"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"138","DOI":"10.4274\/balkanmedj.galenos.2020.2019.8.25","article-title":"The Impact of Pre-transplant Cell-free DNA Levels on Leukemia Relapse and Transplant-related Complications in Allogeneic Hematopoietic Stem Cell Transplant Recipients","volume":"37","author":"Yegin","year":"2020","journal-title":"Balk. Med. J."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2682","DOI":"10.1182\/blood-2018-10-880690","article-title":"Prognostic impact of circulating tumor DNA status post-allogeneic hematopoietic stem cell transplantation in AML and MDS","volume":"133","author":"Nakamura","year":"2019","journal-title":"Blood"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3233\/CBM-170657","article-title":"Low miR-192 expression predicts poor prognosis in pediatric acute myeloid leukemia","volume":"22","author":"Tian","year":"2018","journal-title":"Cancer Biomark."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1186\/s13000-015-0345-6","article-title":"Low expression of circulating microRNA-328 is associated with poor prognosis in patients with acute myeloid leukemia","volume":"10","author":"Liu","year":"2015","journal-title":"Diagn. Pathol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"255","DOI":"10.3109\/00365548.2014.985711","article-title":"Human plasma cell-free DNA as a predictor of infectious complications of neutropenic fever in hematological patients","volume":"47","author":"Purhonen","year":"2015","journal-title":"Infect. Dis."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1080\/15321819.2019.1668407","article-title":"Detection of NRAS G12D and NRAS G13C mutant genes among apparently healthy and haematologic malignant individuals in Federal Capital Territory, Nigeria","volume":"40","author":"Anyanwu","year":"2019","journal-title":"J. Immunoass. Immunochem."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/s41698-019-0102-5","article-title":"Liquid biopsy for minimal residual disease detection in leukemia using a portable blast cell biochip","volume":"3","author":"Khoo","year":"2019","journal-title":"Npj Precis. Oncol."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Dueck, M.E., Lin, R., Zayac, A., Gallagher, S., Chao, A.K., Jiang, L., Datwani, S.S., Hung, P., and Stieglitz, E. (2019). Precision cancer monitoring using a novel, fully integrated, microfluidic array partitioning digital PCR platform. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-55872-7"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1080\/10428194.2018.1499905","article-title":"Circulating microRNAs expression profile in newly diagnosed and imatinib treated chronic phase\u2014Chronic myeloid leukemia","volume":"60","author":"Ferreira","year":"2019","journal-title":"Leuk. Lymphoma"},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Martins, J.R.B., de Moraes, L.N., Cury, S.S., Dadalto, J., Capannacci, J., Carvalho, R.F., Nogueira, C.R., Hokama, N.K., and Hokama, P.O.M. (2020). Comparison of microRNA Expression Profile in Chronic Myeloid Leukemia Patients Newly Diagnosed and Treated by Allogeneic Hematopoietic Stem Cell Transplantation. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.01544"},{"key":"ref_99","first-page":"2133","article-title":"Feasibility of tumor-derived exosome enrichment in the onco-hematology leukemic model of chronic myeloid leukemia","volume":"44","author":"Bernardi","year":"2019","journal-title":"Int. J. Mol. Med."},{"key":"ref_100","unstructured":"Institut Curie (2023, June 11). Molecular and Immunological Characterisation of High Risk CHildhood Cancer at DiagnOsis, Treatment and Follow-Up\u2014Biological Evaluation in Children, Adolescents and Young Adults\u2014[Internet], Available online: https:\/\/clinicaltrials.gov\/study\/NCT03496402."},{"key":"ref_101","unstructured":"Ziegler, D.D. (2023, June 11). A Multicenter Prospective Study of the Feasibility and Clinical Value of a Diagnostic Service for Identifying Therapeutic Targets and Recommending Personalised Treatment for Children and Adolescents with High-Risk Cancer [Internet], Available online: https:\/\/clinicaltrials.gov\/study\/NCT03336931."},{"key":"ref_102","unstructured":"Australian & New Zealand Children\u2019s Haematology\/Oncology Group (2023, June 11). Precision Medicine for Every Child with Cancer [Internet], Available online: https:\/\/clinicaltrials.gov\/study\/NCT05504772."},{"key":"ref_103","unstructured":"University Health Network, Toronto (2023, June 11). Liquid Biopsy Evaluation and Repository Development at Princess Margaret [Internet], Available online: https:\/\/clinicaltrials.gov\/study\/NCT03702309."},{"key":"ref_104","unstructured":"Adela, Inc. (2023, June 11). cfDNA Assay Multicenter Prospective Observational Validation for Early Cancer Detection, Minimal Residual Disease, and Relapse [Internet], Available online: https:\/\/clinicaltrials.gov\/study\/NCT05366881."},{"key":"ref_105","unstructured":"Gustave Roussy, Cancer Campus, Grand Paris (2023, June 11). MoleculAr Profiling for Pediatric and Young Adult Cancer Treatment Stratification 2 [Internet], Available online: https:\/\/clinicaltrials.gov\/study\/NCT05691608."},{"key":"ref_106","unstructured":"Centre Leon Berard (2023, June 11). A Prospective Longitudinal Profiling Program of Cancer Patients with Sequential Tumor and Liquid Biopsies [Internet], Available online: https:\/\/clinicaltrials.gov\/study\/NCT05099068."},{"key":"ref_107","unstructured":"Bond, D. (2023, June 11). A Phase I Study of Duvelisib in Combination with Nivolumab for Patients With Richter\u2019s Syndrome and Transformed Follicular Lymphoma [Internet], Available online: https:\/\/clinicaltrials.gov\/study\/NCT03892044."},{"key":"ref_108","unstructured":"Cyclacel Pharmaceuticals, Inc (2023, June 11). A Phase 1\/2, Open Label, Multicenter Study to Investigate the Safety and Efficacy of Fadraciclib (CYC065), an Oral CDK 2\/9 Inhibitor, in Subjects with Leukemias or Myelodysplastic Syndrome (MDS) [Internet], Available online: https:\/\/clinicaltrials.gov\/study\/NCT05168904."},{"key":"ref_109","unstructured":"Ghia, P. (2023, June 11). Lymph Node Microenvironment Modifications in Patients with CLL Treated with Venetoclax-Based Regimens [Internet], Available online: https:\/\/clinicaltrials.gov\/study\/NCT04790045."},{"key":"ref_110","unstructured":"St. Jude Children\u2019s Research Hospital (2023, June 11). A Phase I and Expansion Cohort Study of Selinexor and Venetoclax in Combination with Chemotherapy in Pediatric and Young Adult Patients with Refractory or Relapsed Acute Myeloid Leukemia [Internet], Available online: https:\/\/clinicaltrials.gov\/study\/NCT04898894."},{"key":"ref_111","unstructured":"Cramer, P. (2024, July 01). A Prospective, Open-label, Multicenter Phase-II Trial to Evaluate the Efficacy and Safety of a Sequential Regimen of Bendamustine Followed by GA101 (Obinutuzumab), Acalabrutinib (ACP-196) and ABT-199 (Venetoclax) in Patients with Relapsed\/Refractory CLL (CLL2-BAAG Protocol) [Internet], Available online: https:\/\/clinicaltrials.gov\/study\/nct03787264."},{"key":"ref_112","unstructured":"Rossi, D. (2023, June 11). Prospective, Observational, Multi-Centred, Non-Interventional Study on the Identification of Biomarkers That Are Predictive of Early Ibrutinib Treatment Failure in High Risk TP53 Mutated Chronic Lymphocytic Leukemia [Internet], Available online: https:\/\/clinicaltrials.gov\/study\/NCT02827617."},{"key":"ref_113","unstructured":"Qian, L. (2023, June 11). Monitoring Circulating Tumor DNA After Chemotherapy in Elderly Patients with Acute Leukemia [Internet], Available online: https:\/\/clinicaltrials.gov\/study\/NCT04157569."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Della Starza, I., De Novi, L.A., Elia, L., Bellomarino, V., Beldinanzi, M., Soscia, R., Cardinali, D., Chiaretti, S., Guarini, A., and Fo\u00e0, R. (2023). Optimizing Molecular Minimal Residual Disease Analysis in Adult Acute Lymphoblastic Leukemia. Cancers, 15.","DOI":"10.3390\/cancers15020374"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"e396","DOI":"10.1097\/MPH.0000000000002419","article-title":"Assessment of Minimal Residual Disease in Childhood Acute Lymphoblastic Leukemia: A Multicenter Study From Turkey","volume":"44","author":"Evim","year":"2022","journal-title":"J. Pediatr. Hematol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"665","DOI":"10.3390\/jcm4040665","article-title":"Current Approaches in the Treatment of Relapsed and Refractory Acute Myeloid Leukemia","volume":"4","author":"Ramos","year":"2015","journal-title":"J. Clin. Med."},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Del Giudice, I., Raponi, S., Della Starza, I., De Propris, M.S., Cavalli, M., De Novi, L.A., Cappelli, L.V., Ilari, C., Cafforio, L., and Guarini, A. (2019). Minimal Residual Disease in Chronic Lymphocytic Leukemia: A New Goal?. Front. Oncol., 9.","DOI":"10.3389\/fonc.2019.00689"},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Pihlak, R., Fong, C., and Starling, N. (2023). Targeted Therapies and Developing Precision Medicine in Gastric Cancer. Cancers, 15.","DOI":"10.3390\/cancers15123248"},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Luceno, C.F., Jeon, W.J., Samaeekia, R., Shin, J., and Sonpavde, G.P. (2023). Precision Medicine to Treat Urothelial Carcinoma\u2014The Way Forward. Cancers, 15.","DOI":"10.3390\/cancers15113024"},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Mohanty, S.K., Lobo, A., Mishra, S.K., and Cheng, L. (2023). Precision Medicine in Bladder Cancer: Present Challenges and Future Directions. J. Pers. Med., 13.","DOI":"10.3390\/jpm13050756"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1007\/s11899-022-00674-4","article-title":"Precision Medicine in Myeloid Malignancies: Hype or Hope?","volume":"17","author":"Khanal","year":"2022","journal-title":"Curr. Hematol. Malig. Rep."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/9\/1438\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:21:21Z","timestamp":1760030481000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/9\/1438"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,25]]},"references-count":121,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["cancers17091438"],"URL":"https:\/\/doi.org\/10.3390\/cancers17091438","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,25]]}}}