Evaluating the chemoresistant effect of poor prognosis-associated gene IGJ overexpression in a B-acute lymphoblastic leukemia model

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dc.contributor.advisorGodoy Silva, Rubén Daríospa
dc.contributor.advisorGutierrez Triana, José Arturospa
dc.contributor.authorMoreno Cristancho, Camilo Ernestospa
dc.contributor.orcidhttps://orcid.org/0000-0002-0402-0530spa
dc.contributor.researchgroupGrupo de Investigación en Procesos Químicos y Bioquímicosspa
dc.date.accessioned2024-06-07T21:22:53Z
dc.date.available2024-06-07T21:22:53Z
dc.date.issued2024
dc.descriptionilustraciones, diagramasspa
dc.description.abstractLa Leucemia Linfoblástica Aguda (LLA) es una neoplasia hematológica que se caracteriza por la proliferación desordenada de células progenitoras de linaje linfoide B o T, siendo comúnmente diagnosticada en la población pediátrica y mostrando agresividad en adultos. A pesar de que Colombia ocupa el tercer lugar mundial en incidencia de LLA, la información sobre perfiles genéticos específicos en su población es insuficiente. En estudios recientes con pacientes adultos colombianos con LLA-B, tanto respondedores como no respondedores al tratamiento quimioterapéutico de inducción, se identificó un perfil con elevada expresión simultánea de los genes IGJ (Immunoglobulin J polypeptide), ID3 (DNA-binding protein inhibitor 3) e ID1 (DNA-binding protein inhibitor 1). Sin embargo, La relevancia funcional de esta firma génica de mal pronóstico en LLA-B, especialmente la del gen IGJ, es desconocida al carecer de información asociada con la quimiorresistencia. En este trabajo, establecimos un modelo celular de LLA-B con la sobreexpresión del gen de mal pronóstico IGJ utilizando la activación transcripcional mediada por CRISPR (IGJ_CRISPRa) para evaluar posibles alteraciones en la actividad metabólica y la resistencia a agentes quimioterapéuticos comúnmente utilizados en el tratamiento de la LLA. El análisis de RT-qPCR de las células IGJ_CRISPRa demostró un aumento sustancial en la expresión del gen endógeno IGJ a las 96, 120 y 144 horas después de la nucleofección, junto con alteraciones menores en la expresión génica de ID3 e ID1. Además, la evaluación de la actividad metabólica y la quimiorresistencia en las células IGJ_CRISPRa reveló un aumento en la actividad metabólica y la resistencia a dexametasona, metotrexato, doxorrubicina, y un aumento moderado en la resistencia a citarabina. Esto sugiere una posible asociación entre el gen IGJ y los mecanismos epigenéticos que alteran la expresión génica y las vías metabólicas. (Texto tomado de la fuente).spa
dc.description.abstractAcute Lymphoblastic Leukemia (ALL) is a hematologic neoplasm characterized by the disordered proliferation of progenitor cells of B or T lymphoid lineage, commonly diagnosed in the pediatric population, and exhibiting aggressiveness in adults. Despite Colombia ranking third globally in ALL incidences, specific genetic profiles in its population are insufficiently documented. Recent studies with Colombian adult patients diagnosed with B-cell ALL identified a profile with simultaneous overexpression of genes IGJ (Immunoglobulin J polypeptide), ID3 (DNA-binding protein inhibitor 3), and ID1 (DNA-binding protein inhibitor 1). However, the functional relevance of this adverse genetic signature in B-cell ALL, especially regarding the IGJ gene, remains unknown due to a lack of information associated with chemoresistance. In this study, we established a B-cell ALL cellular model with overexpression of the poor prognostic gene IGJ using CRISPR-mediated transcriptional activation (IGJ_CRISPRa) to assess potential alterations in metabolic activity and resistance to chemotherapeutic agents commonly used in ALL treatment. RT-qPCR analysis of IGJ_CRISPRa cells demonstrated a substantial increase in the expression of the IGJ endogenous gene at 96, 120, and 144 hours after nucleofection, along with minor alterations in the gene expression of ID3 and ID1. In addition, the evaluation of metabolic activity and chemoresistance in IGJ_CRISPRa cells revealed an increase in metabolic activity and resistance to dexamethasone, methotrexate, doxorubicin, and a moderate increase in resistance to cytarabine. This suggests a potential association between the IGJ gene and epigenetic mechanisms that alter gene expression and metabolic pathways.eng
dc.description.degreelevelMaestríaspa
dc.description.degreenameMagíster en Ingeniería - Ingeniería Químicaspa
dc.description.notesTexto en inglésspa
dc.description.researchareaBiotecnologíaspa
dc.format.extentxviii, 83 páginasspa
dc.format.mimetypeapplication/pdfspa
dc.identifier.instnameUniversidad Nacional de Colombiaspa
dc.identifier.reponameRepositorio Institucional Universidad Nacional de Colombiaspa
dc.identifier.repourlhttps://repositorio.unal.edu.co/spa
dc.identifier.urihttps://repositorio.unal.edu.co/handle/unal/86219
dc.language.isoengspa
dc.publisherUniversidad Nacional de Colombiaspa
dc.publisher.branchUniversidad Nacional de Colombia - Sede Bogotáspa
dc.publisher.facultyFacultad de Ingenieríaspa
dc.publisher.placeBogotá, Colombiaspa
dc.publisher.programBogotá - Ingeniería - Maestría en Ingeniería - Ingeniería Químicaspa
dc.relation.indexedBiremespa
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dc.rights.accessrightsinfo:eu-repo/semantics/openAccessspa
dc.rights.licenseAtribución-NoComercial 4.0 Internacionalspa
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/spa
dc.subject.ddc570 - Biología::576 - Genética y evoluciónspa
dc.subject.ddc660 - Ingeniería química::668 - Tecnología de otros productos orgánicosspa
dc.subject.ddc610 - Medicina y salud::615 - Farmacología y terapéuticaspa
dc.subject.decsCadenas J de Inmunoglobulinaspa
dc.subject.decsImmunoglobulin J-Chainseng
dc.subject.decseucemia-Linfoma Linfoblástico de Células Precursorasspa
dc.subject.decsPrecursor Cell Lymphoblastic Leukemia-Lymphomaeng
dc.subject.decsResistencia a Antineoplásicosspa
dc.subject.decsDrug Resistance, Neoplasmeng
dc.subject.proposalLeucemia linfoblástica agudaspa
dc.subject.proposalGenes pronósticos adversosspa
dc.subject.proposalCRISPRaspa
dc.subject.proposalActividad metabólicaspa
dc.subject.proposalQuimioterapia del cáncerspa
dc.subject.proposalAcute lymphoblastic leukemiaeng
dc.subject.proposalAdverse prognostic geneseng
dc.subject.proposalCRISPRaeng
dc.subject.proposalMetabolic activityeng
dc.subject.proposalCancer chemotherapyeng
dc.titleEvaluating the chemoresistant effect of poor prognosis-associated gene IGJ overexpression in a B-acute lymphoblastic leukemia modeleng
dc.title.translatedEvaluación del efecto quimiorresistente de la sobreexpresión del gen asociado a mal pronóstico IGJ en un modelo de leucemia linfoblástica aguda de precursores Bspa
dc.typeTrabajo de grado - Maestríaspa
dc.type.coarhttp://purl.org/coar/resource_type/c_bdccspa
dc.type.coarversionhttp://purl.org/coar/version/c_ab4af688f83e57aaspa
dc.type.contentTextspa
dc.type.driverinfo:eu-repo/semantics/masterThesisspa
dc.type.redcolhttp://purl.org/redcol/resource_type/TMspa
dc.type.versioninfo:eu-repo/semantics/acceptedVersionspa
dcterms.audience.professionaldevelopmentEstudiantesspa
dcterms.audience.professionaldevelopmentInvestigadoresspa
dcterms.audience.professionaldevelopmentPúblico generalspa
oaire.accessrightshttp://purl.org/coar/access_right/c_abf2spa

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