Hematopoietic stem and progenitor cell-restricted Cdx2 expression induces transformation to myelodysplasia and acute leukemia
Journal article
Vu, Therese, Straube, Jasmin, Porter, Amy H., Bywater, Megan, Song, Axia, Ling, Victoria, Cooper, Leanne, Pali, Gabor, Bruedigam, Claudia, Jacquelin, Sebastien, Green, Joanne, Magor, Graham, Perkins, Andrew, Chalk, Alistair M., Walkley, Carl R., Heidel, Florian H., Mukhopadhyay, Pamela, Cloonan, Nicole, Gröschel, Stefan, ... Lane, Steven W.. (2020). Hematopoietic stem and progenitor cell-restricted Cdx2 expression induces transformation to myelodysplasia and acute leukemia. Nature Communications. 11, pp. 1-15. https://doi.org/10.1038/s41467-020-16840-2
Authors | Vu, Therese, Straube, Jasmin, Porter, Amy H., Bywater, Megan, Song, Axia, Ling, Victoria, Cooper, Leanne, Pali, Gabor, Bruedigam, Claudia, Jacquelin, Sebastien, Green, Joanne, Magor, Graham, Perkins, Andrew, Chalk, Alistair M., Walkley, Carl R., Heidel, Florian H., Mukhopadhyay, Pamela, Cloonan, Nicole, Gröschel, Stefan, Mallm, Jan-Philipp, Fröhling, Stefan, Scholl, Claudia and Lane, Steven W. |
---|---|
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 transcription factors. Furthermore, treatment of Cdx2 AML with azacitidine decreases leukemic burden. Extended scheduling of low-dose azacitidine shows greater efficacy in comparison to intermittent higher-dose azacitidine, linked to more specific epigenetic modulation. Conditional Cdx2 expression in HSPCs is an inducible model of de novo leukemic transformation and can be used to optimize treatment in high-risk AML. |
Year | 2020 |
Journal | Nature Communications |
Journal citation | 11, pp. 1-15 |
Publisher | Nature Publishing Group |
ISSN | 2041-1723 |
Digital Object Identifier (DOI) | https://doi.org/10.1038/s41467-020-16840-2 |
Scopus EID | 2-s2.0-85086602290 |
Open access | Published as ‘gold’ (paid) open access |
Research or scholarly | Research |
Page range | 1-15 |
Publisher's version | License File Access Level Open |
Output status | Published |
Publication process dates | |
Deposited | 27 Apr 2021 |
https://acuresearchbank.acu.edu.au/item/8vy47/hematopoietic-stem-and-progenitor-cell-restricted-cdx2-expression-induces-transformation-to-myelodysplasia-and-acute-leukemia
Download files
Publisher's version
OA_Vu_2020_Hematopoietic_stem_and_progenitor_cell_restricted.pdf | |
License: CC BY 4.0 | |
File access level: Open |
85
total views36
total downloads0
views this month0
downloads this month