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Página principal > Artículos > Artículos publicados > Engraftment characterization of risk-stratified AML in NSGS mice |
Fecha: | 2021 |
Resumen: | 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. |
Ayudas: | Ministerio de Economía y Competitividad SAF2016-80481R Ministerio de Economía y Competitividad PID2019-108160RBI00 Instituto de Salud Carlos III PI-0119-2019 Instituto de Salud Carlos III CPII17/00032 Instituto de Salud Carlos III PI17/01028 European Commission 792923 |
Nota: | Altres ajuts: Obra Social La Caixa (LCF/PR/HR19/52160011); Inter-reg V-A programme (POCTEFA) 2014-2020 (grant PROTEO-blood EFA360/19); Health Canada (H4080-144541); Deutsche Josep Carreras Leukamie Stiftung; Asociación Española Contra el Cáncer INVES20011LÓPE, INVES211226MOLI); Fundación Hay Esperanza; CERCA/Generalitat de Catalunya; Lady Tata Memorial Trust International Award. |
Derechos: | 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. |
Lengua: | Anglès |
Documento: | Article ; recerca ; Versió publicada |
Publicado en: | Blood advances, Vol. 5 Núm. 23 (14 2021) , p. 4842-4854, ISSN 2473-9537 |
13 p, 2.6 MB |