miRNome profiling of clonal stem cells in Ph+ CML

Autores
Ruiz, María Sol; Sánchez, María Belén; Bonecker, Simone; Furtado, Carolina; Koile, Daniel Isaac; Yankilevich, Patricio; Cranco, Santiago; Custidiano, María del Rosario; Freitas, Josefina; Moiraghi, Beatriz; Pérez, Mariel Ana; Pavlovsky, Carolina; Varela, Ana Inés; Ventriglia, Verónica; Sánchez Ávalos, Julio César Américo; Larripa, Irene Beatriz; Zalcberg, Ilana; Mordoh, Jose; Valent, Peter; Bianchini, Michele
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Chronic myeloid leukemia (CML) is a myeloid stem cell neoplasm characterized by an expansion of myeloid progenitor cells and the presence of BCR-ABL1 oncoprotein. Since the introduction of specific BCR-ABL1 tyrosine kinase inhibitors (TKI), overall survival has improved significantly. However, under long-term therapy patients may have residual disease that originates from TKI-resistant leukemic stem cells (LSC). In this work, we analyzed the miRNome of CML LSC, normal hematopoietic stem cells (HSC) obtained from the same CML patients, and stem and progenitor cells obtained from healthy donors (HD) by next-generation sequencing. We detected a global decrease of microRNA levels in LSC and HSC from CML patients, and decreased levels of microRNAs and snoRNAs from a genomic cluster in chromosome 14, suggesting a mechanism of silencing of multiple non-coding RNAs. Surprisingly, HSC from CML patients, despite the absence of BCR-ABL1 expression, showed an altered miRNome. In silico analysis revealed an association between validated microRNAs and multiple metabolic pathways, suggesting that these molecules may be mediators of the previously reported dysregulation of LSC metabolism. This is the first report of the LSC miRNome that distinguishes between BCR-ABL1+ LSC and their BCR-ABL1- counterparts, providing valuable data for future studies.
Fil: Ruiz, María Sol. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Sánchez, María Belén. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina
Fil: Bonecker, Simone. Instituto Nacional de Câncer; Brasil
Fil: Furtado, Carolina. Instituto Nacional de Câncer; Brasil
Fil: Koile, Daniel Isaac. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina
Fil: Yankilevich, Patricio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina
Fil: Cranco, Santiago. Instituto Alexander Fleming; Argentina
Fil: Custidiano, María del Rosario. Instituto Alexander Fleming; Argentina
Fil: Freitas, Josefina. Hospital Nacional Profesor Alejandro Posadas; Argentina
Fil: Moiraghi, Beatriz. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina
Fil: Pérez, Mariel Ana. Gobierno de la Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal General de Agudos "prof. Dr. Rodolfo Rossi".; Argentina
Fil: Pavlovsky, Carolina. Fundación Para Combatir la Leucemia; Argentina
Fil: Varela, Ana Inés. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina
Fil: Ventriglia, Verónica. Hospital Nacional Profesor Alejandro Posadas; Argentina
Fil: Sánchez Ávalos, Julio César Américo. Instituto Alexander Fleming; Argentina
Fil: Larripa, Irene Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Zalcberg, Ilana. Instituto Nacional de Câncer; Brasil
Fil: Mordoh, Jose. Fundación Cáncer; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Valent, Peter. Medical University of Vienna; Austria
Fil: Bianchini, Michele. Fundación Cáncer; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
CD26
LEUKEMIA
LEUKEMIC STEM CELL
METABOLISM
MICRORNAS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/168583
Acceder
id CONICETDig_1fdf7fa99983367f53bb0e3198de21bb
oai_identifier_str oai:ri.conicet.gov.ar:11336/168583
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling miRNome profiling of clonal stem cells in Ph+ CMLRuiz, María SolSánchez, María BelénBonecker, SimoneFurtado, CarolinaKoile, Daniel IsaacYankilevich, PatricioCranco, SantiagoCustidiano, María del RosarioFreitas, JosefinaMoiraghi, BeatrizPérez, Mariel AnaPavlovsky, CarolinaVarela, Ana InésVentriglia, VerónicaSánchez Ávalos, Julio César AméricoLarripa, Irene BeatrizZalcberg, IlanaMordoh, JoseValent, PeterBianchini, MicheleCD26LEUKEMIALEUKEMIC STEM CELLMETABOLISMMICRORNAShttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Chronic myeloid leukemia (CML) is a myeloid stem cell neoplasm characterized by an expansion of myeloid progenitor cells and the presence of BCR-ABL1 oncoprotein. Since the introduction of specific BCR-ABL1 tyrosine kinase inhibitors (TKI), overall survival has improved significantly. However, under long-term therapy patients may have residual disease that originates from TKI-resistant leukemic stem cells (LSC). In this work, we analyzed the miRNome of CML LSC, normal hematopoietic stem cells (HSC) obtained from the same CML patients, and stem and progenitor cells obtained from healthy donors (HD) by next-generation sequencing. We detected a global decrease of microRNA levels in LSC and HSC from CML patients, and decreased levels of microRNAs and snoRNAs from a genomic cluster in chromosome 14, suggesting a mechanism of silencing of multiple non-coding RNAs. Surprisingly, HSC from CML patients, despite the absence of BCR-ABL1 expression, showed an altered miRNome. In silico analysis revealed an association between validated microRNAs and multiple metabolic pathways, suggesting that these molecules may be mediators of the previously reported dysregulation of LSC metabolism. This is the first report of the LSC miRNome that distinguishes between BCR-ABL1+ LSC and their BCR-ABL1- counterparts, providing valuable data for future studies.Fil: Ruiz, María Sol. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Sánchez, María Belén. Fundación Cáncer. Centro de Investigaciones Oncológicas; ArgentinaFil: Bonecker, Simone. Instituto Nacional de Câncer; BrasilFil: Furtado, Carolina. Instituto Nacional de Câncer; BrasilFil: Koile, Daniel Isaac. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Yankilevich, Patricio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Cranco, Santiago. Instituto Alexander Fleming; ArgentinaFil: Custidiano, María del Rosario. Instituto Alexander Fleming; ArgentinaFil: Freitas, Josefina. Hospital Nacional Profesor Alejandro Posadas; ArgentinaFil: Moiraghi, Beatriz. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Pérez, Mariel Ana. Gobierno de la Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal General de Agudos "prof. Dr. Rodolfo Rossi".; ArgentinaFil: Pavlovsky, Carolina. Fundación Para Combatir la Leucemia; ArgentinaFil: Varela, Ana Inés. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Ventriglia, Verónica. Hospital Nacional Profesor Alejandro Posadas; ArgentinaFil: Sánchez Ávalos, Julio César Américo. Instituto Alexander Fleming; ArgentinaFil: Larripa, Irene Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Zalcberg, Ilana. Instituto Nacional de Câncer; BrasilFil: Mordoh, Jose. Fundación Cáncer; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Valent, Peter. Medical University of Vienna; AustriaFil: Bianchini, Michele. Fundación Cáncer; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaCold Spring Harbor Laboratory Press2020-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/168583Ruiz, María Sol; Sánchez, María Belén; Bonecker, Simone; Furtado, Carolina; Koile, Daniel Isaac; et al.; miRNome profiling of clonal stem cells in Ph+ CML; Cold Spring Harbor Laboratory Press; BioRxiv; 11; 3-2020; 1-272692-82052692-8205CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/info:eu-repo/semantics/altIdentifier/doi/10.1101/2020.03.16.989194info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:19:29Zoai:ri.conicet.gov.ar:11336/168583instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:19:30.253CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv miRNome profiling of clonal stem cells in Ph+ CML
title miRNome profiling of clonal stem cells in Ph+ CML
spellingShingle miRNome profiling of clonal stem cells in Ph+ CML
Ruiz, María Sol
CD26
LEUKEMIA
LEUKEMIC STEM CELL
METABOLISM
MICRORNAS
title_short miRNome profiling of clonal stem cells in Ph+ CML
title_full miRNome profiling of clonal stem cells in Ph+ CML
title_fullStr miRNome profiling of clonal stem cells in Ph+ CML
title_full_unstemmed miRNome profiling of clonal stem cells in Ph+ CML
title_sort miRNome profiling of clonal stem cells in Ph+ CML
dc.creator.none.fl_str_mv Ruiz, María Sol
Sánchez, María Belén
Bonecker, Simone
Furtado, Carolina
Koile, Daniel Isaac
Yankilevich, Patricio
Cranco, Santiago
Custidiano, María del Rosario
Freitas, Josefina
Moiraghi, Beatriz
Pérez, Mariel Ana
Pavlovsky, Carolina
Varela, Ana Inés
Ventriglia, Verónica
Sánchez Ávalos, Julio César Américo
Larripa, Irene Beatriz
Zalcberg, Ilana
Mordoh, Jose
Valent, Peter
Bianchini, Michele
author Ruiz, María Sol
author_facet Ruiz, María Sol
Sánchez, María Belén
Bonecker, Simone
Furtado, Carolina
Koile, Daniel Isaac
Yankilevich, Patricio
Cranco, Santiago
Custidiano, María del Rosario
Freitas, Josefina
Moiraghi, Beatriz
Pérez, Mariel Ana
Pavlovsky, Carolina
Varela, Ana Inés
Ventriglia, Verónica
Sánchez Ávalos, Julio César Américo
Larripa, Irene Beatriz
Zalcberg, Ilana
Mordoh, Jose
Valent, Peter
Bianchini, Michele
author_role author
author2 Sánchez, María Belén
Bonecker, Simone
Furtado, Carolina
Koile, Daniel Isaac
Yankilevich, Patricio
Cranco, Santiago
Custidiano, María del Rosario
Freitas, Josefina
Moiraghi, Beatriz
Pérez, Mariel Ana
Pavlovsky, Carolina
Varela, Ana Inés
Ventriglia, Verónica
Sánchez Ávalos, Julio César Américo
Larripa, Irene Beatriz
Zalcberg, Ilana
Mordoh, Jose
Valent, Peter
Bianchini, Michele
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv CD26
LEUKEMIA
LEUKEMIC STEM CELL
METABOLISM
MICRORNAS
topic CD26
LEUKEMIA
LEUKEMIC STEM CELL
METABOLISM
MICRORNAS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Chronic myeloid leukemia (CML) is a myeloid stem cell neoplasm characterized by an expansion of myeloid progenitor cells and the presence of BCR-ABL1 oncoprotein. Since the introduction of specific BCR-ABL1 tyrosine kinase inhibitors (TKI), overall survival has improved significantly. However, under long-term therapy patients may have residual disease that originates from TKI-resistant leukemic stem cells (LSC). In this work, we analyzed the miRNome of CML LSC, normal hematopoietic stem cells (HSC) obtained from the same CML patients, and stem and progenitor cells obtained from healthy donors (HD) by next-generation sequencing. We detected a global decrease of microRNA levels in LSC and HSC from CML patients, and decreased levels of microRNAs and snoRNAs from a genomic cluster in chromosome 14, suggesting a mechanism of silencing of multiple non-coding RNAs. Surprisingly, HSC from CML patients, despite the absence of BCR-ABL1 expression, showed an altered miRNome. In silico analysis revealed an association between validated microRNAs and multiple metabolic pathways, suggesting that these molecules may be mediators of the previously reported dysregulation of LSC metabolism. This is the first report of the LSC miRNome that distinguishes between BCR-ABL1+ LSC and their BCR-ABL1- counterparts, providing valuable data for future studies.
Fil: Ruiz, María Sol. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Sánchez, María Belén. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina
Fil: Bonecker, Simone. Instituto Nacional de Câncer; Brasil
Fil: Furtado, Carolina. Instituto Nacional de Câncer; Brasil
Fil: Koile, Daniel Isaac. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina
Fil: Yankilevich, Patricio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina
Fil: Cranco, Santiago. Instituto Alexander Fleming; Argentina
Fil: Custidiano, María del Rosario. Instituto Alexander Fleming; Argentina
Fil: Freitas, Josefina. Hospital Nacional Profesor Alejandro Posadas; Argentina
Fil: Moiraghi, Beatriz. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina
Fil: Pérez, Mariel Ana. Gobierno de la Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal General de Agudos "prof. Dr. Rodolfo Rossi".; Argentina
Fil: Pavlovsky, Carolina. Fundación Para Combatir la Leucemia; Argentina
Fil: Varela, Ana Inés. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina
Fil: Ventriglia, Verónica. Hospital Nacional Profesor Alejandro Posadas; Argentina
Fil: Sánchez Ávalos, Julio César Américo. Instituto Alexander Fleming; Argentina
Fil: Larripa, Irene Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Zalcberg, Ilana. Instituto Nacional de Câncer; Brasil
Fil: Mordoh, Jose. Fundación Cáncer; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Valent, Peter. Medical University of Vienna; Austria
Fil: Bianchini, Michele. Fundación Cáncer; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Chronic myeloid leukemia (CML) is a myeloid stem cell neoplasm characterized by an expansion of myeloid progenitor cells and the presence of BCR-ABL1 oncoprotein. Since the introduction of specific BCR-ABL1 tyrosine kinase inhibitors (TKI), overall survival has improved significantly. However, under long-term therapy patients may have residual disease that originates from TKI-resistant leukemic stem cells (LSC). In this work, we analyzed the miRNome of CML LSC, normal hematopoietic stem cells (HSC) obtained from the same CML patients, and stem and progenitor cells obtained from healthy donors (HD) by next-generation sequencing. We detected a global decrease of microRNA levels in LSC and HSC from CML patients, and decreased levels of microRNAs and snoRNAs from a genomic cluster in chromosome 14, suggesting a mechanism of silencing of multiple non-coding RNAs. Surprisingly, HSC from CML patients, despite the absence of BCR-ABL1 expression, showed an altered miRNome. In silico analysis revealed an association between validated microRNAs and multiple metabolic pathways, suggesting that these molecules may be mediators of the previously reported dysregulation of LSC metabolism. This is the first report of the LSC miRNome that distinguishes between BCR-ABL1+ LSC and their BCR-ABL1- counterparts, providing valuable data for future studies.
publishDate 2020
dc.date.none.fl_str_mv 2020-03
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/168583
Ruiz, María Sol; Sánchez, María Belén; Bonecker, Simone; Furtado, Carolina; Koile, Daniel Isaac; et al.; miRNome profiling of clonal stem cells in Ph+ CML; Cold Spring Harbor Laboratory Press; BioRxiv; 11; 3-2020; 1-27
2692-8205
2692-8205
CONICET Digital
CONICET
url http://hdl.handle.net/11336/168583
identifier_str_mv Ruiz, María Sol; Sánchez, María Belén; Bonecker, Simone; Furtado, Carolina; Koile, Daniel Isaac; et al.; miRNome profiling of clonal stem cells in Ph+ CML; Cold Spring Harbor Laboratory Press; BioRxiv; 11; 3-2020; 1-27
2692-8205
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/
info:eu-repo/semantics/altIdentifier/doi/10.1101/2020.03.16.989194
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Cold Spring Harbor Laboratory Press
publisher.none.fl_str_mv Cold Spring Harbor Laboratory Press
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1844614167383769088
score 13.070432

Publicaciones similares