Acute myeloid leukemia xenograft success prediction: saving time
journal contributionposted on 05.08.2020, 16:30 by Emmanuel Griessinger, Jacques Vargaftig, Stuart Horswell, David C Taussig, John Gribben, Dominique Bonnet
Xenograft assay allows functional analysis of leukemia-initiating cells of acute myeloid leukemia primary samples. However, 40% of samples derived from patients with better outcomes fail to engraft in immunodeficient mouse recipients when conventional protocols are followed. At diagnosis, the engraftment of intermediate-risk group samples cannot be anticipated. In this study, we decided to further explore the reasons for xenograft success and failure. No differences in extracellular phenotype, apoptosis, or cell cycle profile could distinguish samples that engraft (engrafter [E]) from samples that do not engraft (nonengrafter [NE]) in NSG mice. In addition, ex vivo long-term culture assay revealed, after 5 weeks, a lower content of leukemic-LTC-initiating cells in the NE samples associated with a lower expansion rate capacity. One-week co-cultures with mesenchymal or osteoblastic or endothelial cells did not influence the proliferation rate, suggesting that E and NE samples are genuinely rapidly or slowly expanding independent of external cue. Engraftment success for some NE samples was consistently observed in recipient mice analyzed 6 months later than the conventional 3-month period. Eventually we implemented a flow cytometry-based assay, which allowed us to predict, in 1 week, the fast or delayed engraftment potential of a noncharacterized acute myeloid leukemia sample. This approach will be especially useful in selecting intermediate-risk-group patient samples and restricting the experimental duration to a 3-month period and, eventually, in reducing the number of animals and the cost and effort of unnecessary xenograft failures.