Page 21 - Haematologica June

Editorials
autologous MSC (auto). These results are very interesting because previous publications from two other groups arrived at opposite conclusions.18-20 Krevvata et al. confirm the observation of Rouault-Pierre et al. and demonstrate that MDS only offer transient benefit from the cytokine stimulation in the NSG-S model, and actually tend to exhaust their engraftment level over time.2 It is also the first study presenting a comprehensive paired analysis of engraftment that clearly establishes that MDS engraft- ment is not enhanced by co-injection of MSC, in contrast to previous reports. Overall, this work suggests that improving the MDS xenograft model remains a key chal- lenge. Further testing should be performed using other newly developed immunodeficient mouse models, such as the four genes encoding human cytokines MISTRG (M-CSFh/h IL-3/GM-CSFh/h hSIRPAtg TPOh/h Rag2-/- Il2rg-/-) strain or NBSGW mice (mouse stem cell factor receptor mutated in the background of NSG), to eventu- ally develop better MDS xenografts. In the perspective of this study, future investigations could explore and try to understand how and why an IL3, SCF and GM-SCF cytokine cocktail can be beneficial for supporting LICs of good prognosis AML but not of MDS, and how their dis- tinct epigenetic regulators and DNA methylation patterns might be involved in this differential response.
Acknowledgments
EG is supported by a grant from the Fondation de France.
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