Evaluating the chemoresistant effect of poor prognosis-associated gene IGJ overexpression in a B-acute lymphoblastic leukemia model
ilustraciones, diagramas
- Autores:
-
Moreno Cristancho, Camilo Ernesto
- Tipo de recurso:
- Fecha de publicación:
- 2024
- Institución:
- Universidad Nacional de Colombia
- Repositorio:
- Universidad Nacional de Colombia
- Idioma:
- eng
- OAI Identifier:
- oai:repositorio.unal.edu.co:unal/86219
- Palabra clave:
- 570 - Biología::576 - Genética y evolución
660 - Ingeniería química::668 - Tecnología de otros productos orgánicos
610 - Medicina y salud::615 - Farmacología y terapéutica
Cadenas J de Inmunoglobulina
eucemia-Linfoma Linfoblástico de Células Precursoras
Resistencia a Antineoplásicos
Immunoglobulin J-Chains
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Drug Resistance, Neoplasm
Leucemia linfoblástica aguda
Genes pronósticos adversos
CRISPRa
Actividad metabólica
Quimioterapia del cáncer
Acute lymphoblastic leukemia
Adverse prognostic genes
CRISPRa
Metabolic activity
Cancer chemotherapy
- Rights
- openAccess
- License
- Atribución-NoComercial 4.0 Internacional
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Universidad Nacional de Colombia |
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| dc.title.eng.fl_str_mv |
Evaluating the chemoresistant effect of poor prognosis-associated gene IGJ overexpression in a B-acute lymphoblastic leukemia model |
| dc.title.translated.spa.fl_str_mv |
Evaluación del efecto quimiorresistente de la sobreexpresión del gen asociado a mal pronóstico IGJ en un modelo de leucemia linfoblástica aguda de precursores B |
| title |
Evaluating the chemoresistant effect of poor prognosis-associated gene IGJ overexpression in a B-acute lymphoblastic leukemia model |
| spellingShingle |
Evaluating the chemoresistant effect of poor prognosis-associated gene IGJ overexpression in a B-acute lymphoblastic leukemia model 570 - Biología::576 - Genética y evolución 660 - Ingeniería química::668 - Tecnología de otros productos orgánicos 610 - Medicina y salud::615 - Farmacología y terapéutica Cadenas J de Inmunoglobulina eucemia-Linfoma Linfoblástico de Células Precursoras Resistencia a Antineoplásicos Immunoglobulin J-Chains Precursor Cell Lymphoblastic Leukemia-Lymphoma Drug Resistance, Neoplasm Leucemia linfoblástica aguda Genes pronósticos adversos CRISPRa Actividad metabólica Quimioterapia del cáncer Acute lymphoblastic leukemia Adverse prognostic genes CRISPRa Metabolic activity Cancer chemotherapy |
| title_short |
Evaluating the chemoresistant effect of poor prognosis-associated gene IGJ overexpression in a B-acute lymphoblastic leukemia model |
| title_full |
Evaluating the chemoresistant effect of poor prognosis-associated gene IGJ overexpression in a B-acute lymphoblastic leukemia model |
| title_fullStr |
Evaluating the chemoresistant effect of poor prognosis-associated gene IGJ overexpression in a B-acute lymphoblastic leukemia model |
| title_full_unstemmed |
Evaluating the chemoresistant effect of poor prognosis-associated gene IGJ overexpression in a B-acute lymphoblastic leukemia model |
| title_sort |
Evaluating the chemoresistant effect of poor prognosis-associated gene IGJ overexpression in a B-acute lymphoblastic leukemia model |
| dc.creator.fl_str_mv |
Moreno Cristancho, Camilo Ernesto |
| dc.contributor.advisor.spa.fl_str_mv |
Godoy Silva, Rubén Darío Gutierrez Triana, José Arturo |
| dc.contributor.author.spa.fl_str_mv |
Moreno Cristancho, Camilo Ernesto |
| dc.contributor.researchgroup.spa.fl_str_mv |
Grupo de Investigación en Procesos Químicos y Bioquímicos |
| dc.contributor.orcid.spa.fl_str_mv |
https://orcid.org/0000-0002-0402-0530 |
| dc.subject.ddc.spa.fl_str_mv |
570 - Biología::576 - Genética y evolución 660 - Ingeniería química::668 - Tecnología de otros productos orgánicos 610 - Medicina y salud::615 - Farmacología y terapéutica |
| topic |
570 - Biología::576 - Genética y evolución 660 - Ingeniería química::668 - Tecnología de otros productos orgánicos 610 - Medicina y salud::615 - Farmacología y terapéutica Cadenas J de Inmunoglobulina eucemia-Linfoma Linfoblástico de Células Precursoras Resistencia a Antineoplásicos Immunoglobulin J-Chains Precursor Cell Lymphoblastic Leukemia-Lymphoma Drug Resistance, Neoplasm Leucemia linfoblástica aguda Genes pronósticos adversos CRISPRa Actividad metabólica Quimioterapia del cáncer Acute lymphoblastic leukemia Adverse prognostic genes CRISPRa Metabolic activity Cancer chemotherapy |
| dc.subject.decs.spa.fl_str_mv |
Cadenas J de Inmunoglobulina eucemia-Linfoma Linfoblástico de Células Precursoras Resistencia a Antineoplásicos |
| dc.subject.decs.eng.fl_str_mv |
Immunoglobulin J-Chains Precursor Cell Lymphoblastic Leukemia-Lymphoma Drug Resistance, Neoplasm |
| dc.subject.proposal.spa.fl_str_mv |
Leucemia linfoblástica aguda Genes pronósticos adversos CRISPRa Actividad metabólica Quimioterapia del cáncer |
| dc.subject.proposal.eng.fl_str_mv |
Acute lymphoblastic leukemia Adverse prognostic genes CRISPRa Metabolic activity Cancer chemotherapy |
| description |
ilustraciones, diagramas |
| publishDate |
2024 |
| dc.date.accessioned.none.fl_str_mv |
2024-06-07T21:22:53Z |
| dc.date.available.none.fl_str_mv |
2024-06-07T21:22:53Z |
| dc.date.issued.none.fl_str_mv |
2024 |
| dc.type.spa.fl_str_mv |
Trabajo de grado - Maestría |
| dc.type.driver.spa.fl_str_mv |
info:eu-repo/semantics/masterThesis |
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info:eu-repo/semantics/acceptedVersion |
| dc.type.content.spa.fl_str_mv |
Text |
| dc.type.redcol.spa.fl_str_mv |
http://purl.org/redcol/resource_type/TM |
| status_str |
acceptedVersion |
| dc.identifier.uri.none.fl_str_mv |
https://repositorio.unal.edu.co/handle/unal/86219 |
| dc.identifier.instname.spa.fl_str_mv |
Universidad Nacional de Colombia |
| dc.identifier.reponame.spa.fl_str_mv |
Repositorio Institucional Universidad Nacional de Colombia |
| dc.identifier.repourl.spa.fl_str_mv |
https://repositorio.unal.edu.co/ |
| url |
https://repositorio.unal.edu.co/handle/unal/86219 https://repositorio.unal.edu.co/ |
| identifier_str_mv |
Universidad Nacional de Colombia Repositorio Institucional Universidad Nacional de Colombia |
| dc.language.iso.spa.fl_str_mv |
eng |
| language |
eng |
| dc.relation.indexed.spa.fl_str_mv |
Bireme |
| dc.relation.references.spa.fl_str_mv |
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Atribución-NoComercial 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Godoy Silva, Rubén Darío019810b6b9f5c2a275ca1c832cf9cda7600Gutierrez Triana, José Arturoa6771eeaec99d8019e68b43a45d4baa1600Moreno Cristancho, Camilo Ernestof45c40448ce987469f30f0e49facc6adGrupo de Investigación en Procesos Químicos y Bioquímicoshttps://orcid.org/0000-0002-0402-05302024-06-07T21:22:53Z2024-06-07T21:22:53Z2024https://repositorio.unal.edu.co/handle/unal/86219Universidad Nacional de ColombiaRepositorio Institucional Universidad Nacional de Colombiahttps://repositorio.unal.edu.co/ilustraciones, diagramasLa 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).Acute 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.Texto en inglésMaestríaMagíster en Ingeniería - Ingeniería QuímicaBiotecnologíaxviii, 83 páginasapplication/pdfengUniversidad Nacional de ColombiaBogotá - Ingeniería - Maestría en Ingeniería - Ingeniería QuímicaFacultad de IngenieríaBogotá, ColombiaUniversidad Nacional de Colombia - Sede Bogotá570 - Biología::576 - Genética y evolución660 - Ingeniería química::668 - Tecnología de otros productos orgánicos610 - Medicina y salud::615 - Farmacología y terapéuticaCadenas J de Inmunoglobulinaeucemia-Linfoma Linfoblástico de Células PrecursorasResistencia a AntineoplásicosImmunoglobulin J-ChainsPrecursor Cell Lymphoblastic Leukemia-LymphomaDrug Resistance, NeoplasmLeucemia linfoblástica agudaGenes pronósticos adversosCRISPRaActividad metabólicaQuimioterapia del cáncerAcute lymphoblastic leukemiaAdverse prognostic genesCRISPRaMetabolic activityCancer chemotherapyEvaluating the chemoresistant effect of poor prognosis-associated gene IGJ overexpression in a B-acute lymphoblastic leukemia modelEvaluación del efecto quimiorresistente de la sobreexpresión del gen asociado a mal pronóstico IGJ en un modelo de leucemia linfoblástica aguda de precursores BTrabajo de grado - Maestríainfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/acceptedVersionTexthttp://purl.org/redcol/resource_type/TMBiremeM. 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Vo et al., “mTORC1 inhibition induces resistance to methotrexate and 6-mercaptopurine in Ph+ and Ph-like B-ALL,” Mol Cancer Ther, vol. 16, no. 9, pp. 1942–1953, Sep. 2017, doi: 10.1158/1535-7163.MCT-17-0024.EstudiantesInvestigadoresPúblico generalLICENSElicense.txtlicense.txttext/plain; charset=utf-85879https://repositorio.unal.edu.co/bitstream/unal/86219/1/license.txteb34b1cf90b7e1103fc9dfd26be24b4aMD51ORIGINAL1026587046.2024.pdf1026587046.2024.pdfTesis de Maestría en Ingeniería - Ingeniería Químicaapplication/pdf3352146https://repositorio.unal.edu.co/bitstream/unal/86219/3/1026587046.2024.pdf65e9c1a775f72d331693ee229065e0e9MD53THUMBNAIL1026587046.2024.pdf.jpg1026587046.2024.pdf.jpgGenerated Thumbnailimage/jpeg5987https://repositorio.unal.edu.co/bitstream/unal/86219/4/1026587046.2024.pdf.jpg224dc8f74f9cac262fc9e587f70868d6MD54unal/86219oai:repositorio.unal.edu.co:unal/862192024-08-25 23:11:19.825Repositorio Institucional Universidad Nacional de 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