Relación entre la expresión de ID1 e ID3 y el microambiente tumoral inmune de la médula ósea en adultos con leucemia linfoblástica aguda de células precursoras B

Ilustraciones a color, diagramas

Autores:
Poveda Garavito, Jenny Nathaly
Tipo de recurso:
Fecha de publicación:
2024
Institución:
Universidad Nacional de Colombia
Repositorio:
Universidad Nacional de Colombia
Idioma:
spa
OAI Identifier:
oai:repositorio.unal.edu.co:unal/86560
Acceso en línea:
https://repositorio.unal.edu.co/handle/unal/86560
https://repositorio.unal.edu.co/
Palabra clave:
610 - Medicina y salud
Sistema Inmunológico
Médula ósea
Monitorización Inmunológica
Immune System
Bone Marrow
Monitoring, Immunologic
Leucemia linfoblástica
Lymphoblastic leukemia
Leucemia linfoblástica aguda de células B precursoras
Sistema inmunitario
Médula ósea
Microambiente
Inmunovigilancia
ID1
ID3
Rights
openAccess
License
Atribución-NoComercial 4.0 Internacional
id UNACIONAL2_1a63f93f77e6acbf294f3b8639d97d35
oai_identifier_str oai:repositorio.unal.edu.co:unal/86560
network_acronym_str UNACIONAL2
network_name_str Universidad Nacional de Colombia
repository_id_str
dc.title.spa.fl_str_mv Relación entre la expresión de ID1 e ID3 y el microambiente tumoral inmune de la médula ósea en adultos con leucemia linfoblástica aguda de células precursoras B
dc.title.translated.none.fl_str_mv Relationship between ID1 and ID3 expression and the bone marrow immune tumor microenvironment in adults with B precursor cell acute lymphoblastic leukemia
title Relación entre la expresión de ID1 e ID3 y el microambiente tumoral inmune de la médula ósea en adultos con leucemia linfoblástica aguda de células precursoras B
spellingShingle Relación entre la expresión de ID1 e ID3 y el microambiente tumoral inmune de la médula ósea en adultos con leucemia linfoblástica aguda de células precursoras B
610 - Medicina y salud
Sistema Inmunológico
Médula ósea
Monitorización Inmunológica
Immune System
Bone Marrow
Monitoring, Immunologic
Leucemia linfoblástica
Lymphoblastic leukemia
Leucemia linfoblástica aguda de células B precursoras
Sistema inmunitario
Médula ósea
Microambiente
Inmunovigilancia
ID1
ID3
title_short Relación entre la expresión de ID1 e ID3 y el microambiente tumoral inmune de la médula ósea en adultos con leucemia linfoblástica aguda de células precursoras B
title_full Relación entre la expresión de ID1 e ID3 y el microambiente tumoral inmune de la médula ósea en adultos con leucemia linfoblástica aguda de células precursoras B
title_fullStr Relación entre la expresión de ID1 e ID3 y el microambiente tumoral inmune de la médula ósea en adultos con leucemia linfoblástica aguda de células precursoras B
title_full_unstemmed Relación entre la expresión de ID1 e ID3 y el microambiente tumoral inmune de la médula ósea en adultos con leucemia linfoblástica aguda de células precursoras B
title_sort Relación entre la expresión de ID1 e ID3 y el microambiente tumoral inmune de la médula ósea en adultos con leucemia linfoblástica aguda de células precursoras B
dc.creator.fl_str_mv Poveda Garavito, Jenny Nathaly
dc.contributor.advisor.none.fl_str_mv Combita Rojas, Alba Lucía
Orozco Castaño, Carlos Alberto
dc.contributor.author.none.fl_str_mv Poveda Garavito, Jenny Nathaly
dc.contributor.researchgroup.spa.fl_str_mv Grupo de Investigación en Biología del Cáncer
Grupo de Investigación Traslacional en Oncología
dc.contributor.orcid.spa.fl_str_mv 0009-0000-6605-873X
Poveda Garavito, Jenny Nathaly [0009-0000-6605-873X]
dc.contributor.cvlac.spa.fl_str_mv Poveda Garavito, Jenny Nathaly [0000074526]
dc.contributor.researchgate.spa.fl_str_mv https://www.researchgate.net/profile/Jenny-Poveda-Garavito
dc.subject.ddc.spa.fl_str_mv 610 - Medicina y salud
topic 610 - Medicina y salud
Sistema Inmunológico
Médula ósea
Monitorización Inmunológica
Immune System
Bone Marrow
Monitoring, Immunologic
Leucemia linfoblástica
Lymphoblastic leukemia
Leucemia linfoblástica aguda de células B precursoras
Sistema inmunitario
Médula ósea
Microambiente
Inmunovigilancia
ID1
ID3
dc.subject.other.spa.fl_str_mv Sistema Inmunológico
Médula ósea
Monitorización Inmunológica
dc.subject.other.eng.fl_str_mv Immune System
Bone Marrow
Monitoring, Immunologic
dc.subject.lemb.spa.fl_str_mv Leucemia linfoblástica
dc.subject.lemb.eng.fl_str_mv Lymphoblastic leukemia
dc.subject.proposal.spa.fl_str_mv Leucemia linfoblástica aguda de células B precursoras
Sistema inmunitario
Médula ósea
Microambiente
Inmunovigilancia
dc.subject.proposal.none.fl_str_mv ID1
ID3
description Ilustraciones a color, diagramas
publishDate 2024
dc.date.accessioned.none.fl_str_mv 2024-07-18T15:11:19Z
dc.date.available.none.fl_str_mv 2024-07-18T15:11:19Z
dc.date.issued.none.fl_str_mv 2024-05-08
dc.type.spa.fl_str_mv Trabajo de grado - Maestría
dc.type.driver.spa.fl_str_mv info:eu-repo/semantics/masterThesis
dc.type.version.spa.fl_str_mv 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/86560
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/86560
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 spa
language spa
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dc.publisher.spa.fl_str_mv Universidad Nacional de Colombia
dc.publisher.program.spa.fl_str_mv Bogotá - Medicina - Maestría en Inmunología
dc.publisher.faculty.spa.fl_str_mv Facultad de Medicina
dc.publisher.place.spa.fl_str_mv Bogotá, Colombia
dc.publisher.branch.spa.fl_str_mv Universidad Nacional de Colombia - Sede Bogotá
institution Universidad Nacional de Colombia
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spelling Atribución-NoComercial 4.0 Internacionalinfo:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Combita Rojas, Alba Lucía6314d25773a6df920534c402dcbbd1b1Orozco Castaño, Carlos Alberto5f6790e238d62c49e2a0516f16a95af6Poveda Garavito, Jenny Nathalya09d2ee2279726b8399cbf11215904bfGrupo de Investigación en Biología del CáncerGrupo de Investigación Traslacional en Oncología0009-0000-6605-873XPoveda Garavito, Jenny Nathaly [0009-0000-6605-873X]Poveda Garavito, Jenny Nathaly [0000074526]https://www.researchgate.net/profile/Jenny-Poveda-Garavito2024-07-18T15:11:19Z2024-07-18T15:11:19Z2024-05-08https://repositorio.unal.edu.co/handle/unal/86560Universidad Nacional de ColombiaRepositorio Institucional Universidad Nacional de Colombiahttps://repositorio.unal.edu.co/Ilustraciones a color, diagramasEl diagnóstico de leucemia linfoblástica aguda de precursores de células B (BCP-ALL) es una condición que generalmente presenta un pronóstico desfavorable. Investigaciones previas identificaron los genes ID1 e ID3 como predictores de mala respuesta en pacientes adultos colombianos con BCP-ALL, genes que desempeñan un papel crucial en diversos procesos relacionados con el desarrollo del cáncer. En particular, en otros modelos de cáncer, ID1 e ID3 se asociaron con la presencia de poblaciones inmunitarias reguladoras en el microambiente inmunitario tumoral (TIME). Considerando que estudios anteriores han demostrado que el desarrollo de BCP-ALL altera la composición de las células inmunitarias y el microambiente tumoral de la médula ósea (BM), influyendo en la progresión de la enfermedad y la respuesta a la terapia, este estudio tuvo como objetivo analizar la expresión diferencial de ID1 e ID3 y su posible relación con el TIME en pacientes con BCP-ALL. Para llevar a cabo el estudio, se tomaron muestras de BM de seis pacientes con BCP-ALL diagnosticados en el Instituto Nacional de Cancerología de Colombia. Inicialmente, se evaluó la expresión de ID1 e ID3 en células tumorales de BM mediante la técnica de RT-qPCR, dividiendo a los pacientes en dos categorías según la expresión de estos genes (basal y sobreexpresión). Posteriormente, se realizó una caracterización detallada de las poblaciones inmunes presentes en la BM mediante citometría de flujo, abarcando linfocitos T CD4+ (T totales y reguladores), T CD8+, células mieloides supresoras (MDSC), macrófagos (M1 y M2) y natural killer (NK). Además, se llevó a cabo un análisis de RNA-seq para evaluar los genes inmunes asociados con la respuesta contra BCP-ALL, y se analizaron los perfiles TIME utilizando paquetes como DESeq2, CIBERSORT y xCell en RStudio. Además, se consultó la base de datos pública TARGET para corroborar los datos obtenidos. Los resultados revelaron la expresión diferencial de 15,951 genes entre los dos grupos estudiados, con una sobreexpresión destacada de genes asociados con las vías de neutrófilos. El análisis de enriquecimiento de genes mostró una mayor expresión de genes implicados en la degranulación de neutrófilos, la activación de neutrófilos y la inmunidad mediada por neutrófilos. En particular, se observaron diferencias significativas en las poblaciones de neutrófilos, monocitos y linfocitos T CD4+ en pacientes con niveles elevados de ID1 e ID3 en comparación con el grupo con expresión basal. Estos hallazgos fueron consistentes con los datos obtenidos mediante citometría de flujo. En conclusión, los resultados de este estudio sugieren que los niveles de expresión de ID1 e ID3 en células leucémicas (LC) de BCP-ALL están asociados con alteraciones significativas en las poblaciones de TIME, destacando un posible papel inmunomodulador de estos genes, especialmente en las vías de los neutrófilos. Estos hallazgos podrían tener implicaciones importantes para comprender la progresión de la enfermedad y mejorar las estrategias terapéuticas en pacientes con BCP-ALL. (Texto tomado de la fuente)The diagnosis of acute lymphoblastic leukemia of B-cell precursors (BCP-ALL) is a condition that typically carries an unfavorable prognosis. Previous research has identified the genes ID1 and ID3 as predictors of poor response in adult Colombian patients with BCP-ALL. These genes play a crucial role in various processes related to cancer development. Specifically, in other cancer models, ID1 and ID3 have been associated with the presence of regulatory immune populations in the tumor immune microenvironment (TIME). Given that previous studies have demonstrated that the development of BCP-ALL alters the composition of immune cells and the tumor microenvironment in the bone marrow (BM), influencing disease progression and therapy response, this study aimed to analyze the differential expression of ID1 and ID3 and their potential relationship with TIME in BCPALL patients. To conduct the study, BM samples were taken from six patients diagnosed with BCP-ALL at the National Cancer Institute of Colombia. Initially, the expression of ID1 and ID3 in BM tumor cells was evaluated using the RT-qPCR technique, categorizing patients into two groups based on the expression of these genes (basal and overexpression). Subsequently, a detailed characterization of immune cell populations present in BM was performed using flow cytometry, including CD4+ T lymphocytes (total and regulatory), CD8+ T cells, myeloid-derived suppressor cells (MDSC), macrophages (M1 and M2), and natural killer (NK) cells. Additionally, an RNA-seq analysis was conducted to assess immune genes associated with the response against BCP-ALL, and TIME profiles were analyzed using packages such as DESeq2, CIBERSORT, and xCell in RStudio. Furthermore, the public TARGET database was consulted to corroborate the obtained data. The results revealed differential expression of 15,951 genes between the two studied groups, with prominent overexpression of genes associated with neutrophil pathways. Gene enrichment analysis showed increased expression of genes involved in neutrophil degranulation, neutrophil activation, and neutrophil-mediated immunity. Specifically, significant differences were observed in the populations of neutrophils, monocytes, and CD4+ T lymphocytes in patients with elevated levels of ID1 and ID3 compared to the group with basal expression. These findings were consistent with data obtained through flow cytometry. In conclusion, the results of this study suggest that the expression levels of ID1 and ID3 in leukemia cells (LC) of BCP-ALL are associated with significant alterations in TIME populations, highlighting a potential immunomodulatory role of these genes, especially in neutrophil pathways. These findings could have important implications for understanding disease progression and improving therapeutic strategies in BCP-ALL patients.MaestríaMagister en InmunologíaÁspectos Inmunológicos del Cáncerxvi, 83 páginasapplication/pdfspaUniversidad Nacional de ColombiaBogotá - Medicina - Maestría en InmunologíaFacultad de MedicinaBogotá, ColombiaUniversidad Nacional de Colombia - Sede Bogotá610 - Medicina y saludSistema InmunológicoMédula óseaMonitorización InmunológicaImmune SystemBone MarrowMonitoring, ImmunologicLeucemia linfoblásticaLymphoblastic leukemiaLeucemia linfoblástica aguda de células B precursorasSistema inmunitarioMédula óseaMicroambienteInmunovigilanciaID1ID3Relación entre la expresión de ID1 e ID3 y el microambiente tumoral inmune de la médula ósea en adultos con leucemia linfoblástica aguda de células precursoras BRelationship between ID1 and ID3 expression and the bone marrow immune tumor microenvironment in adults with B precursor cell acute lymphoblastic leukemiaTrabajo de grado - Maestríainfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/acceptedVersionTexthttp://purl.org/redcol/resource_type/TM1. 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Cancers (Basel). 2023 Aug 1;15(16):4186.Instituto Nacional de CancerologíaBibliotecariosEstudiantesInvestigadoresMaestrosMedios de comunicaciónPúblico generalLICENSElicense.txtlicense.txttext/plain; charset=utf-85879https://repositorio.unal.edu.co/bitstream/unal/86560/3/license.txteb34b1cf90b7e1103fc9dfd26be24b4aMD53ORIGINAL1012387881.2024.pdf1012387881.2024.pdfTesis de Magister en Inmunologíaapplication/pdf3472839https://repositorio.unal.edu.co/bitstream/unal/86560/4/1012387881.2024.pdfe067efc2612168ee34265728b83e6b87MD54THUMBNAIL1012387881.2024.pdf.jpg1012387881.2024.pdf.jpgGenerated Thumbnailimage/jpeg5585https://repositorio.unal.edu.co/bitstream/unal/86560/5/1012387881.2024.pdf.jpg213f2f0cdf2f5d8f90339e513898a1cdMD55unal/86560oai:repositorio.unal.edu.co:unal/865602024-08-25 23:10:52.837Repositorio Institucional Universidad Nacional de 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