Detailed Characterization of Mesenchymal Stem/Stromal Cells from a Large Cohort of AML Patients Demonstrates a Definitive Link to Treatment Outcomes

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dc.contributor.author	Díaz de la Guardia, Rafael
dc.contributor.author	Lopez-Millan, Belen
dc.contributor.author	Lavoie, Jessie R.
dc.contributor.author	Bueno, Clara
dc.contributor.author	Castaño Cardoso, Julio
dc.contributor.author	Gómez-Casares, Maite
dc.contributor.author	Vives Polo, Susana
dc.contributor.author	Palomo Sanchís, Laura
dc.contributor.author	Juan, Manel
dc.contributor.author	Delgado, Julio
dc.contributor.author	Blanco, Maria L.
dc.contributor.author	Nomdedeu, Josep
dc.contributor.author	Chaparro, Alberto
dc.contributor.author	Fuster, José Luis
dc.contributor.author	Anguita, Eduardo
dc.contributor.author	Rosu-Myles, Michael
dc.contributor.author	Menéndez Bujan, Pablo
dc.contributor.author	Universitat Autònoma de Barcelona
dc.date	2017
dc.identifier	https://ddd.uab.cat/record/186248
dc.identifier	urn:10.1016/j.stemcr.2017.04.019
dc.identifier	urn:oai:ddd.uab.cat:186248
dc.identifier	urn:pmid:28528702
dc.identifier	urn:pmcid:PMC5470078
dc.identifier	urn:pmc-uid:5470078
dc.identifier	urn:articleid:22136711v8p1573
dc.identifier	urn:oai:egreta.uab.cat:publications/60099135-4e5e-4973-9876-0cb9c20af5be
dc.identifier	urn:scopus_id:85019374811
dc.identifier	urn:oai:pubmedcentral.nih.gov:5470078
dc.format	application/pdf
dc.language	eng
dc.publisher
dc.relation	Agència de Gestió d'Ajuts Universitaris i de Recerca SGR/330
dc.relation	European Commission CoG/2014/646903
dc.relation	Ministerio de Economía y Competitividad 2016/RTC/2016/4603-1
dc.relation	Instituto de Salud Carlos III PI14-01191
dc.relation	Stem cell reports ; Vol. 8 (may 2017), p. 1573-1586
dc.rights	open access
dc.rights	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
dc.rights	https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject	BM-MSC
dc.subject	AML
dc.subject	Risk-stratification
dc.subject	Immunosuppression
dc.subject	Characterization
dc.subject	Chemoprotection
dc.subject	IL-10
dc.title	Detailed Characterization of Mesenchymal Stem/Stromal Cells from a Large Cohort of AML Patients Demonstrates a Definitive Link to Treatment Outcomes
dc.type	Article
dc.description.abstract	Altres ajuts: Health Canada's Genomics Research and Development Initiative Phase VI (H4080-144541-2014-2019); Obra Social La Caixa-Fundació Josep Carreras and the Generalitat de Catalunya (SGR330); Asociación Española Contra el Cáncer (AECC-CI-2015)
dc.description.abstract	Bone marrow mesenchymal stem/stromal cells (BM-MSCs) are key components of the hematopoietic niche thought to have a direct role in leukemia pathogenesis. BM-MSCs from patients with acute myeloid leukemia (AML) have been poorly characterized due to disease heterogeneity. We report a functional, genetic, and immunological characterization of BM-MSC cultures from 46 AML patients, stratified by molecular/cytogenetics into low-risk (LR), intermediate-risk (IR), and high-risk (HR) subgroups. Stable MSC cultures were successfully established and characterized from 40 of 46 AML patients irrespective of the risk subgroup. AML-derived BM-MSCs never harbored tumor-specific cytogenetic/molecular alterations present in blasts, but displayed higher clonogenic potential than healthy donor (HD)-derived BM-MSCs. Although HD- and AML-derived BM-MSCs equally provided chemoprotection to AML cells in vitro, AML-derived BM-MSCs were more immunosuppressive/anti-inflammatory, enhanced suppression of lymphocyte proliferation, and diminished secretion of pro-inflammatory cytokines. Multivariate analysis revealed that the level of interleukin-10 produced by AML-derived BM-MSCs as an independent prognostic factor negatively affected overall survival. Collectively our data show that AML-derived BM-MSCs are not tumor related, but display functional differences contributing to therapy resistance and disease evolution. In this article, Díaz de la Guardia and colleagues report a functional, genetic, and immunological characterization of BM-MSC cultures from 46 AML patients, stratified by molecular/cytogenetics into low-risk (LR), intermediate-risk (IR), and high-risk (HR) subgroups. BM-MSCs never harbored tumor-specific cytogenetic/molecular alterations present in blasts, and IL-10 produced by AML-derived BM-MSCs is an independent prognostic factor negatively impacting on overall survival.

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