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Accession IconGSE35504

Engraftment of limited numbers of pediatric leukemia into NOD/SCID/IL2Rcg-null mice enables surrogate markers for clinical outcome

Organism Icon Homo sapiens
Sample Icon 11 Downloadable Samples
Technology Badge Icon Affymetrix Human Gene 1.0 ST Array (hugene10st)

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Description
Cultured immortalized cell lines have been extensively used to study the characteristics of various malignant stem cell clones and to optimize new treatment strategies. Nonetheless, the usefulness of such in vitro systems to recapitulate primary disease proved to be limited. Therefore, the design of more meaningful pre-clinical in vivo models ideally utilizing primary patient-derived material is of critical importance. In this context, the recently described NOD.Cg-Prkdcscid IL2rgtmWjl/Sz (NSG) mouse strain has been reported to sustain superior engraftment rates of patient-derived acute lymphatic and myeloid leukemic samples. However, limited data exist whether NSG-derived blasts retain their leukemogenecity over successive mouse generations and whether characteristics of this mouse model will indeed allow correlation to clinical parameters. In the present study, we thus engrafted NSG mice with 18 different pediatric B cell precursor ALL, AML and T-ALL samples and could demonstrate that NSG-derived blasts retained their leukemogenic profile with respect to immune-phenotype, chromosomal aberrations, transcriptome, flowcytometric- and PCR-minimal residual disease (MRD) marker expression. Moreover, the extent of leukemic engraftment and the overall survival of NSG mice highly correlated with the individual prognosis of pediatric B cell precursor ALL, AML and T-ALL patients. Thus, we here report on a complex in vivo model that provides a valuable tool for studying the heterogeneity of leukemic disease and for improving patient-tailored leukemia-targeting strategies .
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