{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T16:43:29Z","timestamp":1792169009218,"version":"4.4.0"},"reference-count":53,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T00:00:00Z","timestamp":1767916800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004881","name":"Instituto Mexicano del Seguro Social","doi-asserted-by":"publisher","award":["R-2023-785-038"],"award-info":[{"award-number":["R-2023-785-038"]}],"id":[{"id":"10.13039\/501100004881","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Humanidades, Ciencias y Tecnolog\u00edas","doi-asserted-by":"crossref","award":["FORDECYT-PRONACES 302994"],"award-info":[{"award-number":["FORDECYT-PRONACES 302994"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Acute lymphoblastic leukemia (ALL) is a genetically heterogeneous disease where current clinical practice guidelines remain focused on traditional cytogenetic markers. Despite recent advances demonstrating excellent diagnostic accuracy for gene expression signatures, a discontinuity exists between biomarker validation and clinical implementation. This study aimed to develop and validate a multiparametric gene expression signature using digital PCR (dPCR) to accurately diagnose pediatric ALL, with potential utility for monitoring measurable residual disease (MRD). We analyzed 130 bone marrow aspirates from pediatric patients from four clinical groups: non-leukemia, MRD-negative, MRD-positive and leukemia characterized by immunophenotype. Gene expression of an 8-gene panel (JUP, MYC, NT5C3B, GATA3, PTK7, CNP, ICOSLG, and SNAI1) was quantified by dPCR. The diagnostic performance of individual markers was assessed, and a Random Forest machine learning model was trained to classify active disease. The model was validated using a 5-fold stratified cross-validation approach. Individual markers, particularly JUP, MYC, and NT5C3B, showed good diagnostic accuracy for distinguishing leukemia from non-leukemia. However, integrating all eight markers into a multivariate Random Forest model significantly enhanced performance. The model achieved a mean cross-validated area under the curve (AUC) of 0.908 (\u00b10.041) on receiver operator characteristic (ROC) analysis and 0.961 (\u00b10.019) on Precision\u2013Recall (PR) analysis, demonstrating high reliability and a favorable balance between sensitivity and precision. The integrated model achieved high sensitivity (88.9%) for detecting active disease, particularly at initial diagnosis. Although specificity was moderate (65.0%), the high positive predictive value (PPV 85.1%) and accuracy (81.5%) confirm the clinical utility of a positive result. While the panel showed promising performance for distinguishing MRD-positive from MRD-negative samples, the limited MRD-positive cohort size (n = 11) indicates that validation in larger MRD-focused studies is required before clinical implementation for treatment monitoring. This dPCR-based platform provides accessible, quantitative detection without requiring knowledge of clonal shifts or specific genomic landscape, offering potential advantages for resource-limited settings such as those represented in our Mexican pediatric cohort.<\/jats:p>","DOI":"10.3390\/ijms27020674","type":"journal-article","created":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T10:35:52Z","timestamp":1767954952000},"page":"674","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Utility of a Digital PCR-Based Gene Expression Panel for Detection of Leukemic Cells in Pediatric Acute Lymphoblastic Leukemia"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-5610-4041","authenticated-orcid":false,"given":"Jes\u00fas","family":"Garc\u00eda-G\u00f3mez","sequence":"first","affiliation":[{"name":"Programa de Doctorado en Ciencias Biom\u00e9dicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2740-0317","authenticated-orcid":false,"given":"Dalia","family":"Ram\u00edrez-Ram\u00edrez","sequence":"additional","affiliation":[{"name":"Laboratorio de Oncoinmunolog\u00eda y Cit\u00f3mica del C\u00e1ncer Infantil, Centro de Investigaci\u00f3n Biom\u00e9dica de Oriente, Instituto Mexicano del Seguro Social, Puebla 74360, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3401-9757","authenticated-orcid":false,"given":"Rosana","family":"Pelayo","sequence":"additional","affiliation":[{"name":"Laboratorio de Oncoinmunolog\u00eda y Cit\u00f3mica del C\u00e1ncer Infantil, Centro de Investigaci\u00f3n Biom\u00e9dica de Oriente, Instituto Mexicano del Seguro Social, Puebla 74360, Mexico"},{"name":"Unidad de Educaci\u00f3n e Investigaci\u00f3n, Instituto Mexicano del Seguro Social, Mexico City 06725, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8881-1104","authenticated-orcid":false,"given":"Octavio","family":"Mart\u00ednez-Villegas","sequence":"additional","affiliation":[{"name":"Unidad M\u00e9dica de Alta Especialidad, Hospital de Gineco-Pediatr\u00eda No. 48, Centro M\u00e9dico Nacional del Baj\u00edo, Le\u00f3n 37328, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4900-4726","authenticated-orcid":false,"given":"Lauro Fabi\u00e1n","family":"Amador-Medina","sequence":"additional","affiliation":[{"name":"Unidad M\u00e9dica de Alta Especialidad, Hospital de Especialidades No. 1, Centro M\u00e9dico Nacional del Baj\u00edo, Le\u00f3n 37320, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0284-5114","authenticated-orcid":false,"given":"Juan Ram\u00f3n","family":"Gonz\u00e1lez-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Divisi\u00f3n de Gen\u00e9tica, Centro de Investigaci\u00f3n Biom\u00e9dica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara 44340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5628-2041","authenticated-orcid":false,"given":"Augusto","family":"Sarralde-Delgado","sequence":"additional","affiliation":[{"name":"Coordinaci\u00f3n Auxiliar M\u00e9dica de Investigaci\u00f3n en Salud, OOAD Jalisco, Instituto Mexicano del Seguro Social (IMSS), Guadalajara 44340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6209-5031","authenticated-orcid":false,"given":"Luis Felipe","family":"Jave-Su\u00e1rez","sequence":"additional","affiliation":[{"name":"Programa de Doctorado en Ciencias Biom\u00e9dicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Mexico"},{"name":"Divisi\u00f3n de Inmunolog\u00eda, Centro de Investigaci\u00f3n Biom\u00e9dica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara 44340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9288-4824","authenticated-orcid":false,"given":"Adriana","family":"Aguilar-Lemarroy","sequence":"additional","affiliation":[{"name":"Programa de Doctorado en Ciencias Biom\u00e9dicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Mexico"},{"name":"Divisi\u00f3n de Inmunolog\u00eda, Centro de Investigaci\u00f3n Biom\u00e9dica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara 44340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"111356","DOI":"10.1016\/j.isci.2024.111356","article-title":"Global, regional, and national burden of acute lymphoblastic leukemia in children: Epidemiological trends analysis from 1990 to 2021","volume":"27","author":"Hu","year":"2024","journal-title":"iScience"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s12939-019-0940-3","article-title":"Socioeconomic inequalities in survival of children with acute lymphoblastic leukemia insured by social security in Mexico: A study of the 2007\u20132009 cohorts","volume":"18","year":"2019","journal-title":"Int. J. Equity Health"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1533033820928436","DOI":"10.1177\/1533033820928436","article-title":"Poor Prognosis Biomolecular Factors Are Highly Frequent in Childhood Acute Leukemias From Oaxaca, Mexico","volume":"19","author":"Pelayo","year":"2020","journal-title":"Technol. Cancer Res. Treat."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1016\/j.arcmed.2017.01.004","article-title":"Results of Treating Childhood Acute Lymphoblastic Leukemia in a Low-middle Income Country: 10 Year Experience in Northeast Mexico","volume":"47","year":"2016","journal-title":"Arch. Med. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1908","DOI":"10.1038\/leu.2012.120","article-title":"EuroFlow antibody panels for standardized n-dimensional flow cytometric immunophenotyping of normal, reactive and malignant leukocytes","volume":"26","author":"Lhermitte","year":"2012","journal-title":"Leukemia"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1007\/s12308-014-0226-z","article-title":"Flow cytometry in the diagnosis and monitoring of acute leukemia in children","volume":"8","author":"Wood","year":"2015","journal-title":"J. Hematop."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1016\/j.jmoldx.2022.04.014","article-title":"Digital Droplet PCR Is a Reliable Tool to Improve Minimal Residual Disease Stratification in Adult Philadelphia-Negative Acute Lymphoblastic Leukemia","volume":"24","author":"Santoro","year":"2022","journal-title":"J. Mol. Diagn."},{"key":"ref_8","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_9","doi-asserted-by":"crossref","unstructured":"Guan, Y., Zhang, M., Zhang, W., Wang, J., Shen, K., Zhang, K., Yang, L., Huang, L., Wang, N., and Xiao, M. (2021). Clinical Utility of Droplet Digital PCR to Monitor BCR-ABL1 Transcripts of Patients with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Post-chimeric Antigen Receptor19\/22 T-Cell Cocktail Therapy. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.646499"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/j.jmoldx.2022.03.004","article-title":"Digital PCR for Minimal Residual Disease Quantitation Using Immunoglobulin\/T-Cell Receptor Gene Rearrangements in Acute Lymphoblastic Leukemia","volume":"24","author":"Lu","year":"2022","journal-title":"J. Mol. Diagn."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"E11711","DOI":"10.1073\/pnas.1814397115","article-title":"Transcriptional landscape of B cell precursor acute lymphoblastic leukemia based on an international study of 1,223 cases","volume":"115","author":"Li","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1179\/1607845413Y.0000000080","article-title":"Fat1 cadherin provides a novel minimal residual disease marker in acute lymphoblastic leukemia","volume":"18","author":"Ardjmand","year":"2013","journal-title":"Hematology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"6267","DOI":"10.1182\/blood-2010-12-324004","article-title":"New markers for minimal residual disease detection in acute lymphoblastic leukemia","volume":"117","author":"Song","year":"2011","journal-title":"Blood"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Zapata-Garcia, J.A., Riveros-Magana, A.R., Ortiz-Lazareno, P.C., Hernandez-Flores, G., Jave-Suarez, L.F., and Aguilar-Lemarroy, A. (2022). Comparative Genomic Hybridization and Transcriptome Sequencing Reveal Genes with Gain in Acute Lymphoblastic Leukemia: JUP Expression Emerges as a Survival-Related Gene. Diagnostics, 12.","DOI":"10.3390\/diagnostics12112788"},{"key":"ref_15","unstructured":"Mamdouh, A.M., Lim, F.Q., Mi, Y., Olesinski, E.A., Chan, C.G.T., Jasdanwala, S., Lin, X.X., Wang, Y., Tan, J.Y.M., and Bhatia, K.S. (2025). Targetable BIRC5 dependency in therapy-resistant TP53 mutated acute myeloid leukemia. bioRxiv."},{"key":"ref_16","first-page":"1","article-title":"BIRC5 is a prognostic biomarker associated with tumor immune cell infiltration","volume":"11","author":"Xu","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1038\/s41588-022-01159-z","article-title":"The genomic landscape of pediatric acute lymphoblastic leukemia","volume":"54","author":"Brady","year":"2022","journal-title":"Nat. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4486","DOI":"10.1182\/blood-2009-04-218123","article-title":"Gene expression\u2013based classification and regulatory networks of pediatric acute lymphoblastic leukemia","volume":"114","author":"Li","year":"2009","journal-title":"Blood"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1182\/blood-2009-05-218560","article-title":"Gene expression classifiers for relapse-free survival and minimal residual disease improve risk classification and outcome prediction in pediatric B-precursor acute lymphoblastic leukemia","volume":"115","author":"Kang","year":"2010","journal-title":"Blood"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e939","DOI":"10.1097\/HS9.0000000000000939","article-title":"The Gene Expression Classifier ALLCatchR Identifies B-cell Precursor ALL Subtypes and Underlying Developmental Trajectories Across Age","volume":"7","author":"Beder","year":"2023","journal-title":"HemaSphere"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2315","DOI":"10.1182\/blood.V99.7.2315","article-title":"Comparative analysis of Ig and TCR gene rearrangements at diagnosis and at relapse of childhood precursor-B\u2013ALL provides improved strategies for selection of stable PCR targets for monitoring of minimal residual disease","volume":"99","author":"Willemse","year":"2002","journal-title":"Blood"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1038\/sj.leu.2404586","article-title":"Analysis of minimal residual disease by Ig\/TCR gene rearrangements: Guidelines for interpretation of real-time quantitative PCR data","volume":"21","author":"Cazzaniga","year":"2007","journal-title":"Leukemia"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1016\/j.jmoldx.2024.07.004","article-title":"Tailored Digital PCR Follow-Up of Rare Fusion Transcripts after Initial Detection through RNA Sequencing in Hematological Malignancies","volume":"26","author":"Boulland","year":"2024","journal-title":"J. Mol. Diagn."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2318","DOI":"10.1038\/sj.leu.2403135","article-title":"Standardization and quality control studies of \u2018real-time\u2019 quantitative reverse transcriptase polymerase chain reaction of fusion gene transcripts for residual disease detection in leukemia\u2014A Europe Against Cancer Program","volume":"17","author":"Gabert","year":"2003","journal-title":"Leukemia"},{"key":"ref_25","first-page":"1","article-title":"Prevalence of Gene Rearrangements in Mexican Children with Acute Lymphoblastic Leukemia: A Population Study\u2014Report from the Mexican Interinstitutional Group for the Identification of the Causes of Childhood Leukemia","volume":"2014","year":"2014","journal-title":"BioMed Res. Int."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/j.ccell.2019.03.005","article-title":"gamma-Catenin-Dependent Signals Maintain BCR-ABL1(+) B Cell Acute Lymphoblastic Leukemia","volume":"35","author":"Siddiqui","year":"2019","journal-title":"Cancer Cell"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1111\/jop.12952","article-title":"Junction plakoglobin, a potential prognostic marker of oral squamous cell carcinoma, promotes proliferation, migration and invasion","volume":"49","author":"Fang","year":"2020","journal-title":"J. Oral. Pathol. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.2147\/OTT.S230873","article-title":"\u03b3-Catenin Overexpression in AML Patients May Promote Tumor Cell Survival via Activation of the Wnt\/\u03b2-Catenin Axis","volume":"13","author":"Qian","year":"2020","journal-title":"OncoTargets Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1038\/ng.2803","article-title":"Inherited GATA3 variants are associated with Ph-like childhood acute lymphoblastic leukemia and risk of relapse","volume":"45","author":"Roberts","year":"2013","journal-title":"Nat. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1774","DOI":"10.1158\/2159-8290.CD-19-0471","article-title":"GATA3-Controlled Nucleosome Eviction Drives MYC Enhancer Activity in T-cell Development and Leukemia","volume":"9","author":"Belver","year":"2019","journal-title":"Cancer Discov."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Reyes-Le\u00f3n, A., Castro-Vargas, E., Ju\u00e1rez-Vel\u00e1zquez, M.D.R., Mart\u00ednez Anaya, D., Salas-Labad\u00eda, C., Moreno-Lorenzana, D., Galv\u00e1n-D\u00edaz, C.A., L\u00f3pez-Santiago, N., Garc\u00eda-Padilla, E., and Garc\u00eda-Guzm\u00e1n, A.D. (2025). GATA3 germline variants in childhood pre-B acute lymphoblastic leukemia: Association with CRLF2 overexpression and overweight in Mexican patients. Front. Oncol., 15.","DOI":"10.3389\/fonc.2025.1533756"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Nirala, B.K., and Yustein, J.T. (2025). The Role of MYC in Tumor Immune Microenvironment Regulation: Insights and Future Directions. Front. Biosci. Landmark, 30.","DOI":"10.31083\/FBL37304"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1093\/ajcp\/aqab105","article-title":"MYC Expression Is Associated With p53 Expression and TP53 Aberration and Predicts Poor Overall Survival in Acute Lymphoblastic Leukemia\/Lymphoma","volume":"157","author":"Gao","year":"2022","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1038\/nm.3078","article-title":"Activating mutations in the NT5C2 nucleotidase gene drive chemotherapy resistance in relapsed ALL","volume":"19","author":"Tzoneva","year":"2013","journal-title":"Nat. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3327","DOI":"10.1158\/0008-5472.CAN-23-3804","article-title":"An Alternatively Spliced Gain-of-Function NT5C2 Isoform Contributes to Chemoresistance in Acute Lymphoblastic Leukemia","volume":"84","author":"Reglero","year":"2024","journal-title":"Cancer Res."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Kubacka, D., Kozarski, M., Baranowski, M.R., Wojcik, R., Panecka-Hofman, J., Strzelecka, D., Basquin, J., Jemielity, J., and Kowalska, J. (2022). Substrate-Based Design of Cytosolic Nucleotidase IIIB Inhibitors and Structural Insights into Inhibition Mechanism. Pharmaceuticals, 15.","DOI":"10.3390\/ph15050554"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Jin, Z., Guo, T., Zhang, X., Wang, X., and Liu, Y. (2024). PTK7: An underestimated contributor to human cancer. Front. Oncol., 14.","DOI":"10.3389\/fonc.2024.1448695"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"oyae290","DOI":"10.1093\/oncolo\/oyae290","article-title":"Therapeutic targeting of the protein tyrosine kinase-7 in cancer: An overview","volume":"30","author":"Mottard","year":"2025","journal-title":"Oncologist"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1016\/j.leukres.2012.07.004","article-title":"PTK7: A new biomarker for immunophenotypic characterization of maturing T cells and T cell acute lymphoblastic leukemia","volume":"36","author":"Jiang","year":"2012","journal-title":"Leuk. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s40364-021-00270-3","article-title":"Inhibition of BCL11B induces downregulation of PTK7 and results in growth retardation and apoptosis in T-cell acute lymphoblastic leukemia","volume":"9","author":"Li","year":"2021","journal-title":"Biomark. Res."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Jie, Y., Liu, G., Feng, L., Li, Y., E, M., Wu, L., Li, Y., Rong, G., Li, Y., and Wei, H. (2021). PTK7-Targeting CAR T-Cells for the Treatment of Lung Cancer and Other Malignancies. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.665970"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"9581","DOI":"10.1158\/0008-5472.CAN-10-1379","article-title":"Melanoma Cells Express ICOS Ligand to Promote the Activation and Expansion of T-Regulatory Cells","volume":"70","author":"Li","year":"2010","journal-title":"Cancer Res."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Han, Y., Dong, Y., Yang, Q., Xu, W., Jiang, S., Yu, Z., Yu, K., and Zhang, S. (2018). Acute Myeloid Leukemia Cells Express ICOS Ligand to Promote the Expansion of Regulatory T Cells. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.02227"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"104613","DOI":"10.1016\/j.isci.2022.104613","article-title":"The immune checkpoint ICOSLG is a relapse-predicting biomarker and therapeutic target in infant t(4;11) acute lymphoblastic leukemia","volume":"25","author":"Siemund","year":"2022","journal-title":"iScience"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1182\/blood.2019002548","article-title":"The EMT modulator SNAI1 contributes to AML pathogenesis via its interaction with LSD1","volume":"136","author":"Carmichael","year":"2020","journal-title":"Blood"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Li, G., Wang, Y., Wang, W., Lv, G., Li, X., Wang, J., Liu, X., Yuan, D., Deng, S., and You, D. (2024). BIRC5 as a prognostic and diagnostic biomarker in pan-cancer: An integrated analysis of expression, immune subtypes, and functional networks. Front. Genet., 15.","DOI":"10.3389\/fgene.2024.1509342"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.leukres.2003.10.013","article-title":"Differential expression of survivin in bone marrow cells from patients with acute lymphocytic leukemia and chronic lymphocytic leukemia","volume":"28","author":"Nakagawa","year":"2004","journal-title":"Leuk. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"181","DOI":"10.3233\/CBM-150554","article-title":"Survivin and cyclin E2 genes expression in a cohort of Egyptian acute leukemia patients: Clinical importance and future prospects","volume":"16","author":"Makhlouf","year":"2016","journal-title":"Cancer Biomark."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"18261","DOI":"10.1073\/pnas.0606108103","article-title":"NOTCH1 directly regulates c-MYC and activates a feed-forward-loop transcriptional network promoting leukemic cell growth","volume":"103","author":"Palomero","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2315","DOI":"10.1182\/blood-2010-01-262352","article-title":"The cell polarity PTK7 receptor acts as a modulator of the chemotherapeutic response in acute myeloid leukemia and impairs clinical outcome","volume":"116","author":"Prebet","year":"2010","journal-title":"Blood"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Romo-Rodr\u00edguez, R., Zamora-Herrera, G., L\u00f3pez-Blanco, J.A., L\u00f3pez-Garc\u00eda, L., Rosas-Cruz, A., Alfaro-Hern\u00e1ndez, L., Trejo-Pichardo, C.O., Alberto-Aguilar, D.R., Casique-Aguirre, D., and Vilchis-Ordo\u00f1ez, A. (2024). Subclassification of B-acute lymphoblastic leukemia according to age, immunophenotype and microenvironment, predicts MRD risk in Mexican children from vulnerable regions. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1304662"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Alfaro-Hern\u00e1ndez, L., Ram\u00edrez-Ram\u00edrez, D., Romo-Rodr\u00edguez, R., Ayala-Contreras, K., Del Campo-Mart\u00ednez, \u00c1., L\u00f3pez-Aguilar, E., Flores Lujano, J., Allende-L\u00f3pez, A., Alarc\u00f3n-Ruiz, E., and Banos-Lara, M.D.R. (2025). Impact of standardized immunophenotyping and MRD monitoring on early mortality reduction in childhood leukemia: A step towards addressing healthcare disparities in vulnerable populations from Southern Mexico. Front. Oncol., 15.","DOI":"10.3389\/fonc.2025.1614445"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Ye, J., Coulouris, G., Zaretskaya, I., Cutcutache, I., Rozen, S., and Madden, T.L. (2012). Primer-BLAST: A tool to design target-specific primers for polymerase chain reaction. 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