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Engraftment characterization of risk-stratified AML in NSGS mice
dc.contributor.author | Díaz de la Guardia Quiles, Rafael | |
dc.contributor.author | Ramos Mejía, Verónica | |
dc.contributor.author | Rodríguez Manzaneque, Juan Carlos | |
dc.contributor.author | López Millán, Belén | |
dc.date.accessioned | 2022-01-07T13:29:25Z | |
dc.date.available | 2022-01-07T13:29:25Z | |
dc.date.issued | 2021-11-24 | |
dc.identifier.citation | Rafael Díaz de la Guardia... [et al.]. Engraftment characterization of risk-stratified AML in NSGS mice. Blood Adv 2021; 5 (23): 4842–4854. doi: [https://doi.org/10.1182/bloodadvances.2020003958] | es_ES |
dc.identifier.uri | http://hdl.handle.net/10481/72240 | |
dc.description | The authors thank Paola Romecin and Virginia Rodriguez-Cortez for technical assistance. This work was supported by the Spanish Ministry of Economy and Competitiveness (SAF2016-80481R, PID2019-108160RBI00), the Obra Social La Caixa (LCF/PR/HR19/52160011), Interreg V-A programme (POCTEFA) 2014-2020 (grant PROTEOblood EFA360/19), Health Canada (H4080-144541), and Deutsche Josep Carreras Leukämie Stiftung (P.M.). Additional funding was provided by Consejería de Salud y Familia (PI- 0119-2019) (R.D.d.l.G.), Health Institute Carlos III (ISCIII/FEDER, PI17/01028) and Asociación Española Contra el Cáncer (C.B.), Health Institute Carlos III/FEDER (CPII17/00032) (V.R.-M.), and Fundación Hay Esperanza (E.A.). CERCA/Generalitat de Catalunya and Fundación Josep Carreras-Obra Social la Caixa provided institutional support. B.L.-M. was supported by a Lady Tata Memorial Trust International Award and Asociación Española Contra el Cáncer (INVES20011LÓPE). O.M. and T.V.-H. were supported by Asociación Española Contra el Cáncer (INVES211226MOLI) and a Marie Sklodowska Curie Fellowship (792923), respectively. P.M. is an investigator in the Spanish Cell Therapy Network. | es_ES |
dc.description.abstract | Acute myeloid leukemia (AML) is the most common acute leukemia in adults. Disease heterogeneity is well documented, and patient stratification determines treatment decisions. Patient-derived xenografts (PDXs) from risk-stratified AML are crucial for studying AML biology and testing novel therapeutics. Despite recent advances in PDX modeling of AML, reproducible engraftment of human AML is primarily limited to high-risk (HR) cases, with inconsistent or very protracted engraftment observed for favorable-risk (FR) and intermediate-risk (IR) patients. We used NSGS mice to characterize the engraftment robustness/kinetics of 28 AML patient samples grouped according to molecular/ cytogenetic classification and assessed whether the orthotopic coadministration of patientmatched bone marrow mesenchymal stromal cells (BM MSCs) improves AML engraftment. PDX event-free survival correlated well with the predictable prognosis of risk-stratified AML patients. The majority (85-94%) of the mice were engrafted in bone marrow (BM) independently of the risk group, although HR AML patients showed engraftment levels that were significantly superior to those of FR or IR AML patients. Importantly, the engraftment levels observed in NSGS mice by week 6 remained stable over time. Serial transplantation and long-term culture-initiating cell (LTC-IC) assays revealed long-term engraftment limited to HR AML patients, fitter leukemia-initiating cells (LICs) in HR AML samples, and the presence of AML LICs in the CD342 leukemic fraction, regardless of the risk group. Finally, orthotopic coadministration of patient-matched BM MSCs and AML cells was dispensable for BM engraftment levels but favored peripheralization of engrafted AML cells. This comprehensive characterization of human AML engraftment in NSGS mice offers a valuable platform for in vivo testing of targeted therapies in risk-stratified AML patient samples. | es_ES |
dc.description.sponsorship | Spanish Ministry of Economy and Competitiveness (SAF2016-80481R, PID2019-108160RBI00) | es_ES |
dc.description.sponsorship | Obra Social La Caixa (LCF/PR/HR19/52160011) | es_ES |
dc.description.sponsorship | Interreg V-A programme (POCTEFA) 2014-2020 (grant PROTEOblood EFA360/19) | es_ES |
dc.description.sponsorship | Health Canada (H4080-144541) | es_ES |
dc.description.sponsorship | Deutsche Josep Carreras Leukämie Stiftung | es_ES |
dc.description.sponsorship | Consejer ıa de Salud y Familia (PI- 0119-2019) | es_ES |
dc.description.sponsorship | Health Institute Carlos III (ISCIII/FEDER, PI17/01028) | es_ES |
dc.description.sponsorship | Asociación Española Contra el Cáncer | es_ES |
dc.description.sponsorship | Health Institute Carlos III/FEDER (CPII17/00032) | es_ES |
dc.description.sponsorship | Fundación Hay Esperanza | es_ES |
dc.description.sponsorship | CERCA/Generalitat de Catalunya | es_ES |
dc.description.sponsorship | Fundació Josep Carreras-Obra Social la Caixa | es_ES |
dc.description.sponsorship | Lady Tata Memorial Trust International Award | es_ES |
dc.description.sponsorship | Asociación Española Contra el Cáncer (INVES20011LÓPE) | es_ES |
dc.description.sponsorship | Asociación Española Contra el Cáncer (INVES211226MOLI) | es_ES |
dc.description.sponsorship | Marie Sklodowska Curie Fellowship (792923) | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | American Society of Hematology | es_ES |
dc.rights | Atribución-NoComercial-SinDerivadas 3.0 España | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/es/ | * |
dc.title | Engraftment characterization of risk-stratified AML in NSGS mice | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/H2020/792923 | es_ES |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es_ES |
dc.identifier.doi | 10.1182/bloodadvances.2020003958 | |
dc.type.hasVersion | info:eu-repo/semantics/publishedVersion | es_ES |
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