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Asxl1 lesions collaborate with CEBPA-p30 in AML
quences in the context of CEBPA mutant AML and that they therefore provide more than a fertile ground for AML development.
To summarize, we have generated a novel ASXL1G643W mouse model mimicking the most commonly observed ASXL1 lesion mutation in human MDS and AML patients. Consistent with the co-occurrence of CEBPA and ASXL1 lesions in AML, the ASXL1G643W variant accelerates AML development in the context of CEBPA mutant AML. Finally, the observed resistance towards chemotherapy conferred by the ASXL1G643W variant provides us with an experimental handle for future experiments aimed at its reversal.
Disclosures
No conflicts of interest to disclose
Contributions
TD, MBS, AMH and ASW carried out the experiments; TD,
AW, AK, SP and BTP analyzed data; TDA and BP drafted the manuscript which was proofread by all authors; BTP directed the research.
Acknowledgments
We thank Javier Martín Gonzalez and the Transgenic Core Facility for the generation of the mutant strain.
Funding
This work was supported by a grant from the Danish Cancer Society (to Teresa D’Altri) and through a center grant from the Novo Nordisk Foundation (Novo Nordisk Foundation Center for Stem Cell Biology, DanStem; Grant Number NNF17CC0027852). The present work is also part of the Danish Research Center for Precision Medicine in Blood Cancers funded by the Danish Cancer Society grant no. R223-A13071 and Greater Copenhagen Health Science Partners.
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