@misc{10481/72240,
year = {2021},
month = {11},
url = {http://hdl.handle.net/10481/72240},
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.},
organization = {Spanish Ministry of Economy
and Competitiveness (SAF2016-80481R, PID2019-108160RBI00)},
organization = {Obra Social La Caixa (LCF/PR/HR19/52160011)},
organization = {Interreg
V-A programme (POCTEFA) 2014-2020 (grant PROTEOblood
EFA360/19)},
organization = {Health Canada (H4080-144541)},
organization = {Deutsche Josep Carreras Leukämie Stiftung},
organization = {Consejer ıa de Salud y Familia (PI-
0119-2019)},
organization = {Health Institute Carlos III (ISCIII/FEDER, PI17/01028)},
organization = {Asociación Española Contra el Cáncer},
organization = {Health Institute Carlos III/FEDER (CPII17/00032)},
organization = {Fundación Hay Esperanza},
organization = {CERCA/Generalitat de Catalunya},
organization = {Fundació Josep Carreras-Obra Social la Caixa},
organization = {Lady Tata Memorial
Trust International Award},
organization = {Asociación Española Contra el
Cáncer (INVES20011LÓPE)},
organization = {Asociación Española Contra el Cáncer (INVES211226MOLI)},
organization = {Marie Sklodowska Curie Fellowship (792923)},
publisher = {American Society of Hematology},
title = {Engraftment characterization of risk-stratified AML in NSGS mice},
doi = {10.1182/bloodadvances.2020003958},
author = {Díaz de la Guardia Quiles, Rafael and Ramos Mejía, Verónica and Rodríguez Manzaneque, Juan Carlos and López Millán, Belén},
}