Evaluation of the primitive fraction by functional in vitro assays at the RNA and DNA level represents a novel tool for complementing molecular monitoring in chronic myeloid leukem...

Autores: Ruiz, María Sol; Sanchez, María Belén; Gutierrez, Leandro German; Koile, Daniel Isaac; Yankilevich, Patricio; Mosqueira, Celeste; Cranco, Santiago; Custidiano, María del Rosario; Freitas, Josefina; Foncuberta, Cecilia; Moiraghi, Beatriz; Pavlovsky, Carolina; Pérez, Mariel Ana; Ventriglia, Verónica; Sánchez Ávalos, Julio César Américo; Mordoh, Jose; Larripa, Irene Beatriz; Bianchini, Michele
Año de publicación: 2018
Idioma: inglés
Tipo de recurso: artículo
Estado: versión publicada
Descripción: Quantification of BCR-ABL1 mRNA levels in peripheral blood of chronic myeloidleukemia patients is a strong indicator of response to tyrosine-kinase inhibitors (TKI)treatment. However, additional prognostic markers are needed in order to better classify patients. The hypothesis of leukemic stem cells (LSCs) heterogeneity and persistence, suggests that their functional evaluation could be of clinical interest. In this work, we assessed the primitive and progenitor fractions in patients at diagnosis and during TKI treatment using functional in vitro assays, defining a ?functional leukemic burden? (FLB). We observed that the FLB was reduced in vivo in both fractions upon treatment. However, different FLB levels were observed among patients according to their response to treatment, suggesting that quantification of the FLB could complement early molecular monitoring. Given that FLB assessment is limited by BCR-ABL1 mRNA expression levels, we developed a novel detection method of primitive cells at the DNA level, using patient-specific primers and direct nested PCR in colonies obtained from functional in vitro assays. We believe that this methodcould be useful in the context of discontinuation trials, given that it is unknown whether the persistent leukemic clone represents LSCs, able to resume the leukemia upon TKI removal.
Fil: Ruiz, María Sol. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina
Fil: Sanchez, María Belén. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina. Argenomics; Argentina
Fil: Gutierrez, Leandro German. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. Instituto Alexander Fleming, Bs. As.; Argentina
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: Mosqueira, Celeste. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina
Fil: Cranco, Santiago. Fundaleu; Argentina
Fil: Custidiano, María del Rosario. Hospital Italiano de La Plata; Argentina
Fil: Freitas, Josefina. Provincia de Buenos Aires. Hospital Nacional Profesor A. Posadas; Argentina
Fil: Foncuberta, Cecilia. Instituto Alexander Fleming; Argentina
Fil: Moiraghi, Beatriz. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina
Fil: Pavlovsky, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Pérez, Mariel Ana. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina
Fil: Ventriglia, Verónica. Provincia de Buenos Aires. Hospital Nacional Profesor A. Posadas; Argentina; Argentina
Fil: Sánchez Ávalos, Julio César Américo. Instituto Alexander Fleming; Argentina
Fil: Mordoh, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina
Fil: Larripa, Irene Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Bianchini, Michele. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina
Materia: CML
BCR-ABL
Stem Cell
Nivel de accesibilidad: acceso abierto
Condiciones de uso: https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
Institución: Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador: oai:ri.conicet.gov.ar:11336/95943

Acceder

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network_acronym_str	CONICETDig
repository_id_str	3498
network_name_str	CONICET Digital (CONICET)
spelling	Evaluation of the primitive fraction by functional in vitro assays at the RNA and DNA level represents a novel tool for complementing molecular monitoring in chronic myeloid leukemiaRuiz, María SolSanchez, María BelénGutierrez, Leandro GermanKoile, Daniel IsaacYankilevich, PatricioMosqueira, CelesteCranco, SantiagoCustidiano, María del RosarioFreitas, JosefinaFoncuberta, CeciliaMoiraghi, BeatrizPavlovsky, CarolinaPérez, Mariel AnaVentriglia, VerónicaSánchez Ávalos, Julio César AméricoMordoh, JoseLarripa, Irene BeatrizBianchini, MicheleCMLBCR-ABLStem Cellhttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Quantification of BCR-ABL1 mRNA levels in peripheral blood of chronic myeloidleukemia patients is a strong indicator of response to tyrosine-kinase inhibitors (TKI)treatment. However, additional prognostic markers are needed in order to better classify patients. The hypothesis of leukemic stem cells (LSCs) heterogeneity and persistence, suggests that their functional evaluation could be of clinical interest. In this work, we assessed the primitive and progenitor fractions in patients at diagnosis and during TKI treatment using functional in vitro assays, defining a ?functional leukemic burden? (FLB). We observed that the FLB was reduced in vivo in both fractions upon treatment. However, different FLB levels were observed among patients according to their response to treatment, suggesting that quantification of the FLB could complement early molecular monitoring. Given that FLB assessment is limited by BCR-ABL1 mRNA expression levels, we developed a novel detection method of primitive cells at the DNA level, using patient-specific primers and direct nested PCR in colonies obtained from functional in vitro assays. We believe that this methodcould be useful in the context of discontinuation trials, given that it is unknown whether the persistent leukemic clone represents LSCs, able to resume the leukemia upon TKI removal.Fil: Ruiz, María Sol. Fundación Cáncer. Centro de Investigaciones Oncológicas; ArgentinaFil: Sanchez, María Belén. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina. Argenomics; ArgentinaFil: Gutierrez, Leandro German. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. Instituto Alexander Fleming, Bs. As.; ArgentinaFil: 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: Mosqueira, Celeste. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Cranco, Santiago. Fundaleu; ArgentinaFil: Custidiano, María del Rosario. Hospital Italiano de La Plata; ArgentinaFil: Freitas, Josefina. Provincia de Buenos Aires. Hospital Nacional Profesor A. Posadas; ArgentinaFil: Foncuberta, Cecilia. Instituto Alexander Fleming; ArgentinaFil: Moiraghi, Beatriz. Fundación Cáncer. Centro de Investigaciones Oncológicas; ArgentinaFil: Pavlovsky, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Pérez, Mariel Ana. Fundación Cáncer. Centro de Investigaciones Oncológicas; ArgentinaFil: Ventriglia, Verónica. Provincia de Buenos Aires. Hospital Nacional Profesor A. Posadas; Argentina; ArgentinaFil: Sánchez Ávalos, Julio César Américo. Instituto Alexander Fleming; ArgentinaFil: Mordoh, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Cáncer. Centro de Investigaciones Oncológicas; ArgentinaFil: Larripa, Irene Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Bianchini, Michele. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Cáncer. Centro de Investigaciones Oncológicas; ArgentinaImpact Journals2018-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/95943Ruiz, María Sol; Sanchez, María Belén; Gutierrez, Leandro German; Koile, Daniel Isaac; Yankilevich, Patricio; et al.; Evaluation of the primitive fraction by functional in vitro assays at the RNA and DNA level represents a novel tool for complementing molecular monitoring in chronic myeloid leukemia; Impact Journals; Oncotarget; 9; 29; 4-2018; 20255-202641949-2553CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.18632/oncotarget.24749info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:52:40Zoai:ri.conicet.gov.ar:11336/95943instacron: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:34982025-09-03 09:52:41.193CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv	Evaluation of the primitive fraction by functional in vitro assays at the RNA and DNA level represents a novel tool for complementing molecular monitoring in chronic myeloid leukemia
title	Evaluation of the primitive fraction by functional in vitro assays at the RNA and DNA level represents a novel tool for complementing molecular monitoring in chronic myeloid leukemia
spellingShingle	Evaluation of the primitive fraction by functional in vitro assays at the RNA and DNA level represents a novel tool for complementing molecular monitoring in chronic myeloid leukemia Ruiz, María Sol CML BCR-ABL Stem Cell
title_short	Evaluation of the primitive fraction by functional in vitro assays at the RNA and DNA level represents a novel tool for complementing molecular monitoring in chronic myeloid leukemia
title_full	Evaluation of the primitive fraction by functional in vitro assays at the RNA and DNA level represents a novel tool for complementing molecular monitoring in chronic myeloid leukemia
title_fullStr	Evaluation of the primitive fraction by functional in vitro assays at the RNA and DNA level represents a novel tool for complementing molecular monitoring in chronic myeloid leukemia
title_full_unstemmed	Evaluation of the primitive fraction by functional in vitro assays at the RNA and DNA level represents a novel tool for complementing molecular monitoring in chronic myeloid leukemia
title_sort	Evaluation of the primitive fraction by functional in vitro assays at the RNA and DNA level represents a novel tool for complementing molecular monitoring in chronic myeloid leukemia
dc.creator.none.fl_str_mv	Ruiz, María Sol Sanchez, María Belén Gutierrez, Leandro German Koile, Daniel Isaac Yankilevich, Patricio Mosqueira, Celeste Cranco, Santiago Custidiano, María del Rosario Freitas, Josefina Foncuberta, Cecilia Moiraghi, Beatriz Pavlovsky, Carolina Pérez, Mariel Ana Ventriglia, Verónica Sánchez Ávalos, Julio César Américo Mordoh, Jose Larripa, Irene Beatriz Bianchini, Michele
author	Ruiz, María Sol
author_facet	Ruiz, María Sol Sanchez, María Belén Gutierrez, Leandro German Koile, Daniel Isaac Yankilevich, Patricio Mosqueira, Celeste Cranco, Santiago Custidiano, María del Rosario Freitas, Josefina Foncuberta, Cecilia Moiraghi, Beatriz Pavlovsky, Carolina Pérez, Mariel Ana Ventriglia, Verónica Sánchez Ávalos, Julio César Américo Mordoh, Jose Larripa, Irene Beatriz Bianchini, Michele
author_role	author
author2	Sanchez, María Belén Gutierrez, Leandro German Koile, Daniel Isaac Yankilevich, Patricio Mosqueira, Celeste Cranco, Santiago Custidiano, María del Rosario Freitas, Josefina Foncuberta, Cecilia Moiraghi, Beatriz Pavlovsky, Carolina Pérez, Mariel Ana Ventriglia, Verónica Sánchez Ávalos, Julio César Américo Mordoh, Jose Larripa, Irene Beatriz Bianchini, Michele
author2_role	author author author author author author author author author author author author author author author author author
dc.subject.none.fl_str_mv	CML BCR-ABL Stem Cell
topic	CML BCR-ABL Stem Cell
purl_subject.fl_str_mv	https://purl.org/becyt/ford/3.2 https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv	Quantification of BCR-ABL1 mRNA levels in peripheral blood of chronic myeloidleukemia patients is a strong indicator of response to tyrosine-kinase inhibitors (TKI)treatment. However, additional prognostic markers are needed in order to better classify patients. The hypothesis of leukemic stem cells (LSCs) heterogeneity and persistence, suggests that their functional evaluation could be of clinical interest. In this work, we assessed the primitive and progenitor fractions in patients at diagnosis and during TKI treatment using functional in vitro assays, defining a ?functional leukemic burden? (FLB). We observed that the FLB was reduced in vivo in both fractions upon treatment. However, different FLB levels were observed among patients according to their response to treatment, suggesting that quantification of the FLB could complement early molecular monitoring. Given that FLB assessment is limited by BCR-ABL1 mRNA expression levels, we developed a novel detection method of primitive cells at the DNA level, using patient-specific primers and direct nested PCR in colonies obtained from functional in vitro assays. We believe that this methodcould be useful in the context of discontinuation trials, given that it is unknown whether the persistent leukemic clone represents LSCs, able to resume the leukemia upon TKI removal. Fil: Ruiz, María Sol. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina Fil: Sanchez, María Belén. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina. Argenomics; Argentina Fil: Gutierrez, Leandro German. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. Instituto Alexander Fleming, Bs. As.; Argentina 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: Mosqueira, Celeste. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina Fil: Cranco, Santiago. Fundaleu; Argentina Fil: Custidiano, María del Rosario. Hospital Italiano de La Plata; Argentina Fil: Freitas, Josefina. Provincia de Buenos Aires. Hospital Nacional Profesor A. Posadas; Argentina Fil: Foncuberta, Cecilia. Instituto Alexander Fleming; Argentina Fil: Moiraghi, Beatriz. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina Fil: Pavlovsky, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Pérez, Mariel Ana. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina Fil: Ventriglia, Verónica. Provincia de Buenos Aires. Hospital Nacional Profesor A. Posadas; Argentina; Argentina Fil: Sánchez Ávalos, Julio César Américo. Instituto Alexander Fleming; Argentina Fil: Mordoh, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina Fil: Larripa, Irene Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina Fil: Bianchini, Michele. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina
description	Quantification of BCR-ABL1 mRNA levels in peripheral blood of chronic myeloidleukemia patients is a strong indicator of response to tyrosine-kinase inhibitors (TKI)treatment. However, additional prognostic markers are needed in order to better classify patients. The hypothesis of leukemic stem cells (LSCs) heterogeneity and persistence, suggests that their functional evaluation could be of clinical interest. In this work, we assessed the primitive and progenitor fractions in patients at diagnosis and during TKI treatment using functional in vitro assays, defining a ?functional leukemic burden? (FLB). We observed that the FLB was reduced in vivo in both fractions upon treatment. However, different FLB levels were observed among patients according to their response to treatment, suggesting that quantification of the FLB could complement early molecular monitoring. Given that FLB assessment is limited by BCR-ABL1 mRNA expression levels, we developed a novel detection method of primitive cells at the DNA level, using patient-specific primers and direct nested PCR in colonies obtained from functional in vitro assays. We believe that this methodcould be useful in the context of discontinuation trials, given that it is unknown whether the persistent leukemic clone represents LSCs, able to resume the leukemia upon TKI removal.
publishDate	2018
dc.date.none.fl_str_mv	2018-04
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/11336/95943 Ruiz, María Sol; Sanchez, María Belén; Gutierrez, Leandro German; Koile, Daniel Isaac; Yankilevich, Patricio; et al.; Evaluation of the primitive fraction by functional in vitro assays at the RNA and DNA level represents a novel tool for complementing molecular monitoring in chronic myeloid leukemia; Impact Journals; Oncotarget; 9; 29; 4-2018; 20255-20264 1949-2553 CONICET Digital CONICET
url	http://hdl.handle.net/11336/95943
identifier_str_mv	Ruiz, María Sol; Sanchez, María Belén; Gutierrez, Leandro German; Koile, Daniel Isaac; Yankilevich, Patricio; et al.; Evaluation of the primitive fraction by functional in vitro assays at the RNA and DNA level represents a novel tool for complementing molecular monitoring in chronic myeloid leukemia; Impact Journals; Oncotarget; 9; 29; 4-2018; 20255-20264 1949-2553 CONICET Digital CONICET
dc.language.none.fl_str_mv	eng
language	eng
dc.relation.none.fl_str_mv	info:eu-repo/semantics/altIdentifier/doi/10.18632/oncotarget.24749
dc.rights.none.fl_str_mv	info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv	openAccess
rights_invalid_str_mv	https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv	application/pdf application/pdf
dc.publisher.none.fl_str_mv	Impact Journals
publisher.none.fl_str_mv	Impact Journals
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
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score	13.13397

Evaluation of the primitive fraction by functional in vitro assays at the RNA and DNA level represents a novel tool for complementing molecular monitoring in chronic myeloid leukem...

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