{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T09:27:51Z","timestamp":1769765271865,"version":"3.49.0"},"reference-count":40,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T00:00:00Z","timestamp":1759708800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003033","name":"Ministerio de Ciencia, Tecnolog\u00eda e Innovaci\u00f3n","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003033","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2025,12]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n \n B\u2010cell precursor acute lymphoblastic leukemia (B\u2010ALL) is a hematologic malignancy characterized by the uncontrolled proliferation of immature B lymphoblasts. Despite significant advancements in treatment, chemoresistance remains a major challenge. Previous studies, including those involving Colombian patient cohorts, have identified a gene signature involving\n ID1, ID3<\/jats:italic>\n , and\n IGJ<\/jats:italic>\n , which correlates with poor prognosis; however, the underlying mechanisms remain unclear. This study integrates metabolic profiling with gene expression analysis of\n ID1, ID3<\/jats:italic>\n , and\n IGJ<\/jats:italic>\n in patient\u2010derived lymphoblasts. It explores the role of\n IGJ<\/jats:italic>\n overexpression in NALM\u20106 cells to assess its potential contribution to chemoresistance.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Bone marrow samples from 33 newly diagnosed B\u2010ALL patients were analyzed for\n ID1, ID3<\/jats:italic>\n , and\n IGJ<\/jats:italic>\n gene expression. Seahorse XF metabolic assays were conducted on 13 patient samples to assess mitochondrial respiration and glycolytic function. Functional studies were performed in the NALM\u20106 B\u2010ALL cell line using CRISPRa\u2010mediated\n IGJ<\/jats:italic>\n overexpression, followed by metabolic and chemoresistance assays using resazurin\u2010based viability testing with key chemotherapeutic agents.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Patient\u2010derived lymphoblasts exhibited a quiescent metabolic phenotype, with two distinct metabolic subgroups based on oxygen consumption and glycolysis rates. Higher\n IGJ<\/jats:italic>\n expression was significantly associated with the glycolytic subgroup and correlated with worse event\u2010free survival (EFS,\n p<\/jats:italic>\n = 0.0179) and overall survival (OS,\n p<\/jats:italic>\n = 0.0205). In NALM\u20106 cells,\n IGJ<\/jats:italic>\n overexpression led to increased metabolic activity and conferred resistance to dexamethasone, cytarabine, doxorubicin, and methotrexate, but not cyclophosphamide.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n IGJ<\/jats:italic>\n upregulation promotes metabolic reprogramming and chemoresistance in B\u2010ALL, suggesting a potential role for\n IGJ<\/jats:italic>\n as a biomarker and therapeutic target in overcoming treatment resistance. These findings provide new insights into the metabolic mechanisms underlying B\u2010ALL progression and highlight\n IGJ<\/jats:italic>\n as a candidate for future targeted interventions.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/pbc.32068","type":"journal-article","created":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T23:32:09Z","timestamp":1759793529000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Integration of Metabolic Profiling and Functional Genomics Suggests\n IGJ<\/i>\n as a Driver of Chemoresistance in B\u2010ALL"],"prefix":"10.1002","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-4156-7739","authenticated-orcid":false,"given":"Karen Lizeth","family":"Pach\u00f3n\u2010Meza","sequence":"first","affiliation":[{"name":"Immunology and Molecular Epidemiology Research Group (GIEM), Escuela de Microbiologia Facultad De Salud Universidad Industrial de Santander Bucaramanga Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0402-0530","authenticated-orcid":false,"given":"Camilo Ernesto","family":"Moreno\u2010Cristancho","sequence":"additional","affiliation":[{"name":"Immunology and Molecular Epidemiology Research Group (GIEM), Escuela de Microbiologia Facultad De Salud Universidad Industrial de Santander Bucaramanga Colombia"},{"name":"Research Group on Chemical and Biochemical Processes Departamento De Ingenieria Quimica y Ambiental Universidad Nacional de Colombia Bogota Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2019-2447","authenticated-orcid":false,"given":"Jos\u00e9 Luis","family":"Padilla\u2010Agudelo","sequence":"additional","affiliation":[{"name":"Immunology and Molecular Epidemiology Research Group (GIEM), Escuela de Microbiologia Facultad De Salud Universidad Industrial de Santander Bucaramanga Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9578-7480","authenticated-orcid":false,"given":"Ana Isabel","family":"Ramos\u2010Murillo","sequence":"additional","affiliation":[{"name":"Research Group on Chemical and Biochemical Processes Departamento De Ingenieria Quimica y Ambiental Universidad Nacional de Colombia Bogota Colombia"},{"name":"Departamento De Investigaci\u00f3n y Desarrollo, BIOARTIFICIAL BIC Clichy France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0158-5157","authenticated-orcid":false,"given":"Diana","family":"Londo\u00f1o\u2010Barbosa","sequence":"additional","affiliation":[{"name":"Advanced Therapy Unit Instituto Distrital de Ciencia, Biotecnologia e Innovacion en Salud (IDCBIS) Bogota Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5018-9927","authenticated-orcid":false,"given":"Gustavo","family":"Salguero","sequence":"additional","affiliation":[{"name":"Advanced Therapy Unit Instituto Distrital de Ciencia, Biotecnologia e Innovacion en Salud (IDCBIS) Bogota Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7578-790X","authenticated-orcid":false,"given":"Sandra Milena","family":"Sanabria\u2010Barrera","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n Cardiovascular de Colombia Laboratorio De Investigaciones Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3758-640X","authenticated-orcid":false,"given":"Claudia","family":"Chica","sequence":"additional","affiliation":[{"name":"Institut Pasteur Universit\u00e9 Paris Cit\u00e9 Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5849-8011","authenticated-orcid":false,"given":"Nataly","family":"Cruz\u2010Rodriguez","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology University of Michigan Ann Arbor Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6064-3743","authenticated-orcid":false,"given":"Rub\u00e9n Dar\u00edo","family":"Godoy\u2010Silva","sequence":"additional","affiliation":[{"name":"Research Group on Chemical and Biochemical Processes Departamento De Ingenieria Quimica y Ambiental Universidad Nacional de Colombia Bogota Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7705-3173","authenticated-orcid":false,"given":"Jos\u00e9 Arturo","family":"Guti\u00e9rrez\u2010Triana","sequence":"additional","affiliation":[{"name":"Immunology and Molecular Epidemiology Research Group (GIEM), Escuela de Microbiologia Facultad De Salud Universidad Industrial de Santander Bucaramanga Colombia"},{"name":"Laboratorio de Microbiolog\u00eda, CASEM Dpto. 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