Engraftment characterization of risk-stratified AML in NSGS mice

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 therapeutic...

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Detalhes bibliográficos
Autores: Lapillonne, Helene, Díaz de la Guardia, R., Velasco-Hernandez, Talia, Gutiérrez-Agüera, Francisco, Roca-Ho, Heleia, Molina, Òscar, Nombela-Arrieta, Cesar, Bataller Torralba, Alex, Fuster, José Luis, Anguita, Eduardo, Vives, Susana, Zamora, Lurdes, Nomdedéu Guinot, Josep Francesc, Gómez Casares, María Teresa, Ramírez-Orellana, Manuel, Ramos-Mejía, Verónica, Rodriguez-Manzaneque Escribano, Juan Carlos, Bueno, Clara, Lopez Millan, Maria Belén, Menéndez, Pablo
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Recursos:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/218506
Acesso em linha:https://hdl.handle.net/2445/218506
Access Level:acceso abierto
Palavra-chave:Animals
Medul·la òssia
Antígens
Leucèmia
Bone marrow
Antigens
Leukemia
Descrição
Resumo: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 patient-matched 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 CD34 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.

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