RT Journal Article
T1 Engraftment characterization of risk-stratified AML in NSGS mice
A1 Diaz de la Guardia, Rafael
A1 Velasco-Hernandez, Talia
A1 Gutierrez-Aguera, Francisco
A1 Roca-Ho, Heleia
A1 Molina, Oscar
A1 Nombela-Arrieta, Cesar
A1 Bataller, Alex
A1 Luis Fuster, Jose
A1 Anguita, Eduardo
A1 Vives, Susana
A1 Zamora, Lurdes
A1 Nomdedeu, Josep
A1 Teresa Gomez-Casares, Maria
A1 Ramirez-Orellana, Manuel
A1 Lapillonne, Helene
A1 Ramos-Mejia, Veronica
A1 Carlos Rodriguez-Manzaneque, Juan
A1 Bueno, Clara
A1 Lopez-Millan, Belen
A1 Menendez, Pablo
K1 AML biology and
K1 testing novel
K1 We characterize
K1 human AML
K1 Acute myeloid-leukemia
K1 Mesenchymal stem-cells
K1 Initiating cells
K1 Xenotransplantation model
K1 Myelodysplastic syndrome
K1 Progenitor cells
K1 Niche
K1 Nucleophosmin
K1 Frequency
AB 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.
PB Elsevier
SN 2473-9529
YR 2021
FD 2021-11-24
LK https://hdl.handle.net/10668/28398
UL https://hdl.handle.net/10668/28398
LA en
DS RISalud
RD Apr 7, 2025