Journal article

Hematopoietic stem and progenitor cell-restricted Cdx2 expression induces transformation to myelodysplasia and acute leukemia

Therese Vu, Jasmin Straube, Amy H Porter, Megan Bywater, Axia Song, Victoria Ling, Leanne Cooper, Gabor Pali, Claudia Bruedigam, Sebastien Jacquelin, Joanne Green, Graham Magor, Andrew Perkins, Alistair M Chalk, Carl R Walkley, Florian H Heidel, Pamela Mukhopadhyay, Nicole Cloonan, Stefan Groeschel, Jan-Philipp Mallm Show all

Nature Communications | NATURE PUBLISHING GROUP | Published : 2020

Abstract

The caudal-related homeobox transcription factor CDX2 is expressed in leukemic cells but not during normal blood formation. Retroviral overexpression of Cdx2 induces AML in mice, however the developmental stage at which CDX2 exerts its effect is unknown. We developed a conditionally inducible Cdx2 mouse model to determine the effects of in vivo, inducible Cdx2 expression in hematopoietic stem and progenitor cells (HSPCs). Cdx2-transgenic mice develop myelodysplastic syndrome with progression to acute leukemia associated with acquisition of additional driver mutations. Cdx2-expressing HSPCs demonstrate enrichment of hematopoietic-specific enhancers associated with pro-differentiation transcri..

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Grants

Awarded by NHMRC


Funding Acknowledgements

We would like to thank members of the Lane Lab, Geoff Hill, and Kyle MacBeth and Daniel Menezes from Celgene for helpful discussions and input, and Michael Milsom and Ruzhica Bogeska for technical assistance with flow sorting. We are grateful for the expert assistance of the QIMR Berghofer Flow Core, Animal House and Sequencing Core. This work was funded by NHMRC Project Grant 1098470, a philanthropic donation (Gordon and Jessie Gilmour Trust) and a research grant in aid from Celgene. Celgene provided 5-azacitidine for the mouse experiments. S.W.L. is a CSL Centenary Fellow. T.V. received a Leukaemia Foundation of Australia PhD Scholarship.