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
AuthorsVu, 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.

Year2020
JournalNature Communications
Journal citation11, pp. 1-15
PublisherNature Publishing Group
ISSN2041-1723
Digital Object Identifier (DOI)https://doi.org/10.1038/s41467-020-16840-2
Scopus EID2-s2.0-85086602290
Open accessPublished as ‘gold’ (paid) open access
Research or scholarlyResearch
Page range1-15
Publisher's version
License
File Access Level
Open
Output statusPublished
Publication process dates
Deposited27 Apr 2021
Permalink -

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
  • 85
    total views
  • 36
    total downloads
  • 0
    views this month
  • 0
    downloads this month
These values are for the period from 19th October 2020, when this repository was created.

Export as

Related outputs

ADAR1 masks the cancer immunotherapeutic promise of ZBP1-driven necroptosis
Zhang, Ting, Yin, Chaoran, Fedorov, Aleksandr, Qiao, Liangjun, Bao, Hongliang, Beknazarov, Nazar, Wang, Shiyu, Gautam, Avishekh, Williams, Riley M., Crawford, Jeremy Chase, Peri, Suraj, Studitsky, Vasily, Beg, Amer A., Thomas, Paul G., Walkley, Carl, Xu, Yan, Poptsova, Maria, Herbert, Alan and Balachandran, Siddharth. (2022). ADAR1 masks the cancer immunotherapeutic promise of ZBP1-driven necroptosis. Nature. 606, pp. 594-602. https://doi.org/10.1038/s41586-022-04753-7
Genome-wide screening identifies cell-cycle control as a synthetic lethal pathway with SRSF2P95H mutation
Xu, Jane Jialu, Chalk, Alistair M., Nikolic, Iva, Simpson, Kaylene J., Smeets, Monique F. and Walkley, Carl R.. (2022). Genome-wide screening identifies cell-cycle control as a synthetic lethal pathway with SRSF2P95H mutation. Blood Advances. 6(7), pp. 2092-2106. https://doi.org/10.1182/bloodadvances.2021004571
Direct identification of A-to-I editing sites with nanopore native RNA sequencing
Nguyen, Tram, Heng, Jia, Kaewsapsak, Pornchai, Kok, Eng, Stanojevic, Dominik, Liu, Hao, Cardilla, Angelysia, Praditya, Albert, Yi, Zirong, Lin, Mingwan, Aw, Jong, Ho, Yin, Peh, Kai, Wang, Yuanming, Zhong, Qixing, Heraud-Farlow, Jacki, Xue, Shifeng, Reversade, Bruno, Walkley, Carl Richard, ... Tan, Meng. (2022). Direct identification of A-to-I editing sites with nanopore native RNA sequencing. Nature Methods. 19, pp. 833-844. https://doi.org/10.1038/s41592-022-01513-3
Rothmund-Thomson syndrome-like RECQL4 truncating mutations cause a haploinsufficient low-bone-mass phenotype in mice
Castillo-Tandazo, Wilson, Frazier, Ann E., Sims, Natalie A., Smeets, Monique F. and Walkley, Carl R.. (2021). Rothmund-Thomson syndrome-like RECQL4 truncating mutations cause a haploinsufficient low-bone-mass phenotype in mice. Molecular and Cellular Biology. 41(3), pp. Article e00590-20. https://doi.org/10.1128/MCB.00590-20
What do editors do? Understanding the physiological functions of A-to-I RNA editing by adenosine deaminase acting on RNAs
Heraud-Farlow, Jacki E. and Walkley, Carl R.. (2020). What do editors do? Understanding the physiological functions of A-to-I RNA editing by adenosine deaminase acting on RNAs. Open Biology. 10(7), p. 200085. https://doi.org/10.1098/rsob.200085
Enhancing mitochondrial function in vivo rescues MDS-like anemia induced by pRb deficiency
Sen, Taha, Jain, Mayur, Gram, Magnus, Mattebo, Alexander, Soneji, Shamit, Walkley, Carl R. and Singbrant, Sofie. (2020). Enhancing mitochondrial function in vivo rescues MDS-like anemia induced by pRb deficiency. Experimental Hematology. 88, pp. 28-41. https://doi.org/10.1016/j.exphem.2020.06.006
Dynamic regulation of Z-DNA in the mouse prefrontal cortex by the RNA-editing enzyme Adar1 is required for fear extinction
Marshall, Paul R., Zhao, Qiongyi, Li, Xiang, Wei, Wei, Periyakaruppiah, Ambika, Zajaczkowski, Esmi L., J. Leighton, Laura, Madugalle, Sachithrani U., Basic, Dean, Wang, Ziqi, Yin, Jiayu, Liau, Wei-Siang, Gupte, Ankita, Walkley, Carl R. and Bredy, Timothy W.. (2020). Dynamic regulation of Z-DNA in the mouse prefrontal cortex by the RNA-editing enzyme Adar1 is required for fear extinction. Nature Neuroscience. 23(6), pp. 718-729. https://doi.org/10.1038/s41593-020-0627-5
Murine models of bone sarcomas
Jacques, Camille, Renema, Nathalie, Ory, Benjamin, Walkley, Carl R., Grigoriadis, Agamemnon E. and Heymann, Dominique. (2019). Murine models of bone sarcomas. In In Idris, Aymen I. (Ed.). Bone research protocols pp. 331-342 Humana Press. https://doi.org/10.1007/978-1-4939-8997-3_18
Osteosarcoma in the Post Genome Era: Preclinical Models and Approaches to Identify Tractable Therapeutic Targets
Wilson Castillo-Tandazo, Anthony J. Mutsaers and Carl R. Walkley. (2019). Osteosarcoma in the Post Genome Era: Preclinical Models and Approaches to Identify Tractable Therapeutic Targets. Current Osteoporosis Reports. 17(5), pp. 343-352. https://doi.org/10.1007/s11914-019-00534-w
Cell death following the loss of ADAR1 mediated A-to-I RNA editing is not effected by the intrinsic apoptosis pathway
Walkley, Carl R. and Kile, Benjamin T.. (2019). Cell death following the loss of ADAR1 mediated A-to-I RNA editing is not effected by the intrinsic apoptosis pathway. Cell Death and Disease. 10, pp. 1 - 5. https://doi.org/10.1038/s41419-019-2160-6
Defining the functions of adenosine-to-inosine RNA editing through hematology
Heraud-Farlow, Jacki E., Chalk, Alistair M. and Walkley, Carl R.. (2019). Defining the functions of adenosine-to-inosine RNA editing through hematology. Current Opinion in Hematology. 26(4), pp. 241 - 248. https://doi.org/10.1097/MOH.0000000000000514
Modeling human RNA spliceosome mutations in the mouse: Not all mice were created equal
Xu, Jane Jialu, Smeets, Monique F., Tan, Shuh Ying, Wall, Meaghan, Purton, Louise E. and Walkley, Carl R.. (2019). Modeling human RNA spliceosome mutations in the mouse: Not all mice were created equal. Experimental Hematology. 70, pp. 10 - 23. https://doi.org/10.1016/j.exphem.2018.11.001
Hemopoietic Cell Kinase amplification with Protein Tyrosine Phosphatase Receptor T depletion leads to polycythemia, aberrant marrow erythoid maturation, and splenomegaly
Ku, Matthew, MacKinnon, Ruth N., Wall, Meaghan, Narayan, Nisha, Walkley, Carl, Cheng, Heung-Chin, Campbell, Lynda J., Purton, Louise E. and Nandurkar, Harshal. (2019). Hemopoietic Cell Kinase amplification with Protein Tyrosine Phosphatase Receptor T depletion leads to polycythemia, aberrant marrow erythoid maturation, and splenomegaly. Scientific Reports. 9(1), pp. 1 - 11. https://doi.org/10.1038/s41598-019-43373-6
ATP-dependent helicase activity is dispensable for the physiological functions of Recql4
Castillo-Tandazo, Wilson, Smeets, Monique F., Murphy, Vincent, Liu, Rui, Hodson, Charlotte, Heierhorst, Jörg, Deans, Andrew J. and Walkley, Carl R.. (2019). ATP-dependent helicase activity is dispensable for the physiological functions of Recql4. PLoS Genetics. 15(7), pp. 1 - 19. https://doi.org/10.1371/journal.pgen.1008266
The majority of A-to-I RNA editing is not required for mammalian homeostasis
Chalk, Alistair M., Taylor, Scott, Heraud-Farlow, Jacki E. and Walkley, Carl. (2019). The majority of A-to-I RNA editing is not required for mammalian homeostasis. Genome Biology. 20, pp. 1 - 14. https://doi.org/10.1186/s13059-019-1873-2
Smac mimetics LCL161 and GDC-0152 inhibit osteosarcoma growth and metastasis in mice
Shekhar, Tanmay M., Burvenich, Ingrid J. G., Harris, Michael A., Rigopoulos, Angela, Zanker, Damien, Spurling, Alex, Parker, Belinda S., Walkley, Carl R., Scott, Andrew M. and Hawkins, Christine J.. (2019). Smac mimetics LCL161 and GDC-0152 inhibit osteosarcoma growth and metastasis in mice. BMC Cancer. 19, pp. 1 - 18. https://doi.org/10.1186/s12885-019-6103-5
Srsf2P95H initiates myeloid bias and myelodysplastic/myeloproliferative syndrome from hemopoietic stem cells
Smeets, Monique F., Tan, Shuh Ying, Xu, Jane Jialu, Anande, Govardhan, Unnikrishnan, Ashwin, Chalk, Alistair M., Taylor, Scott, Pimanda, John E., Wall, Meaghan, Purton, L. E. and Walkley, Carl. (2018). Srsf2P95H initiates myeloid bias and myelodysplastic/myeloproliferative syndrome from hemopoietic stem cells. Blood. 132(6), pp. 608 - 621. https://doi.org/10.1182/blood-2018-04-845602
Small animal models for the study of bone sarcoma pathogenesis: characteristics, therapeutic interests and limitations
Jacques, Camille, Renema, Nathalie, Lezot, Frederic, Ory, Benjamin, Walkley, Carl, Grigoriadis, Agi E. and Heymann, Dominique. (2018). Small animal models for the study of bone sarcoma pathogenesis: characteristics, therapeutic interests and limitations. Journal of Bone Oncology. 12, pp. 7 - 13. https://doi.org/10.1016/j.jbo.2018.02.004
ADAR1-mediated RNA editing is required for thymic self-tolerance and inhibition of autoimmunity
Nakahama, Taisuke, Kato, Yuki, Kim, Jung In, Vongpipatana, Tuangtong, Suzuki, Yutaka, Walkley, Carl R. and Kawahara, Yukio. (2018). ADAR1-mediated RNA editing is required for thymic self-tolerance and inhibition of autoimmunity. EMBO Reports. 19(12), pp. 1 - 18. https://doi.org/10.15252/embr.201846303
mTORC1 plays an important role in osteoblastic regulation of B-lymphopoiesis
Martin, Sally K., Fitter, Stephen, El Khawanky, Nadia, Grose, Randall H., Walkley, Carl, Purton, Louise E., Ruegg, Markus A., Hall, Michael N., Gronthos, Stan and Zannettino, Andrew C. W.. (2018). mTORC1 plays an important role in osteoblastic regulation of B-lymphopoiesis. Scientific Reports. 8(1), pp. 1 - 10. https://doi.org/10.1038/s41598-018-32858-5
Adar3 is involved in learning and memory in mice
Mladenova, Dessislava, Barry, Guy, Konen, Lyndsey M., Pineda, Sandy S., Guennewig, Boris, Avesson, Lotta, Zinn, Raphael, Schonrock, Nicole, Bitar, Maina, Jonkhout, Nicky, Crumlish, Lauren, Kaczorowski, Dominik C., Gong, Andrew, Pinese, Mark, Franco, Gloria R., Walkley, Carl R., Vissel, Bryce and Mattick, John S.. (2018). Adar3 is involved in learning and memory in mice. Frontiers in Neuroscience. 12, pp. 1 - 17. https://doi.org/10.3389/fnins.2018.00243
Tolerance to sustained activation of the cAMP/Creb pathway activity in osteoblastic cells is enabled by loss of p53
Walia, Mannu K., Taylor, Scott, Ho, Patricia M.W., Martin, John and Walkley, Carl. (2018). Tolerance to sustained activation of the cAMP/Creb pathway activity in osteoblastic cells is enabled by loss of p53. Cell Death and Disease. 9(9), pp. 1 - 17. https://doi.org/10.1038/s41419-018-0944-8
The asymmetric cell division regulators par3, scribble and PINS/GPSM2 are not essential for erythroid development or enucleation
Wölwer, Christina B., Gödde, Nathan, Pase, Luke B., Elsum, Imogen A., Lim, Krystle Y. B., Sacirbegovic, Faruk, Walkley, Carl, Ellis, Sharon, Ohno, Shigeo, Matsuzaki, Fumio, Russell, Sarah M. and Humbert, Patrick O.. (2017). The asymmetric cell division regulators par3, scribble and PINS/GPSM2 are not essential for erythroid development or enucleation. PLoS ONE. 12(1), pp. 1 - 14. https://doi.org/10.1371/journal.pone.0170295
mTORC1 plays an important role in skeletal development by controlling preosteoblast differentiation
Fitter, Stephen, Mathews, Mary P., Martin, Sally K., Xie, Jianling, Ooi, Soo Siang, Walkley, Carl, Codrington, John D., Ruegg, Markus A., Hall, Michael N., Proud, Christopher G., Gronthos, Stan and Zannettino, Andrew C. W.. (2017). mTORC1 plays an important role in skeletal development by controlling preosteoblast differentiation. Molecular and Cellular Biology. 37(7), pp. 1 - 20. https://doi.org/10.1128/MCB.00668-16
Murine models of osteosarcoma: A piece of the translational puzzle
Walia, Mannu K., Castillo-Tandazo, Wilson, Mutsaers, Anthony J., Martin, T. John and Walkley, Carl. (2017). Murine models of osteosarcoma: A piece of the translational puzzle. Journal of Cellular Biochemistry. 119(6), pp. 4241 - 4250. https://doi.org/10.1002/jcb.26601
Ssb1 and Ssb2 cooperate to regulate mouse hematopoietic stem and progenitor cells by resolving replicative stress
Shi, Wei, Vu, Therese, Boucher, Didier, Biernacka, Anna, Nde, Jules, Pandita, Raj K., Straube, Jasmin, Boyle, Glen M., Al-Ejeh, Fares, Nag, Purba, Jeffery, Jessie, Harris, Janelle L., Bain, Amanda L., Grzelak, Marta, Skrzypczak, Magdalena, Mitra, Abhishek, Dojer, Norbert, Crosetto, Nicola, Cloonan, Nicole, ... Khanna, Kum Kum. (2017). Ssb1 and Ssb2 cooperate to regulate mouse hematopoietic stem and progenitor cells by resolving replicative stress. Blood. 129(18), pp. 2479 - 2492. https://doi.org/10.1182/blood-2016-06-725093
Dynamic landscape and regulation of RNA editing in mammals
Tan, Meng How, Li, Qin, Shanmugam, Raghuvaran, Piskol, Robert, Kohler, Jennefer, Young, Amy N., Liu, Kaiwen Ivy, Zhang, Rui, Ramaswami, Gokul, Ariyoshi, Kentaro, Gupte, Ankita, Keegan, Liam P., George, Cyril X., Ramu, Avinash, Huang, Ni, Pollina, Elizabeth A., Leeman, Dena S., Rustighi, Alessandra, Sharon Goh, Y. P., ... GTEx Consortium. (2017). Dynamic landscape and regulation of RNA editing in mammals. Nature. 550, pp. 249 - 254. https://doi.org/10.1038/nature24041
Design, synthesis, and biological activity of 1,2,3-triazolobenzodiazepine BET bromodomain inhibitors
Sharp, Phillip P., Garnier, Jean-Marc, Hatfaludi, Tamas, Xu, Zhen, Segal, David, Jarman, Kate E., Jousset, Hélène, Garnham, Alexandra, Feutrill, John T., Cuzzupe, Anthony, Hall, Peter, Taylor, Scott, Walkley, Carl, Tyler, Dean, Dawson, Mark A., Czabotar, Peter, Wilks, Andrew F., Glaser, Stefan, Huang, David C. S. and Burns, Christopher J.. (2017). Design, synthesis, and biological activity of 1,2,3-triazolobenzodiazepine BET bromodomain inhibitors. ACS Medicinal Chemistry Letters. 8(12), pp. 1298-1303. https://doi.org/10.1021/acsmedchemlett.7b00389
Protein recoding by ADAR1-mediated RNA editing is not essential for normal development and homeostasis
Heraud-Farlow, Jacki E., Chalk, Alistair M., Linder, Sandra, Li, Qin, Taylor, Scott, White, Joshua M., Pang, Lokman, Liddicoat, Brian J., Gupte, Ankita, Li, Jin Billy and Walkley, Carl. (2017). Protein recoding by ADAR1-mediated RNA editing is not essential for normal development and homeostasis. Genome Biology. 18(1), pp. 1 - 18. https://doi.org/10.1186/s13059-017-1301-4
Rewriting the transcriptome: adenosine-to-inosine RNA editing by ADARs
Walkley, Carl and Li, Jin Billy. (2017). Rewriting the transcriptome: adenosine-to-inosine RNA editing by ADARs. Genome Biology. 18(1), pp. 1 - 13. https://doi.org/10.1186/s13059-017-1347-3
ADAR1, inosine and the immune sensing system: Distinguishing self from non-self
Liddicoat, Brian J., Chalk, Alistair M. and Walkley, Carl R.. (2016). ADAR1, inosine and the immune sensing system: Distinguishing self from non-self. Wiley Interdisciplinary Reviews: RNA. 7(2), pp. 157 - 172. https://doi.org/10.1002/wrna.1322
PDGF-AB and 5-Azacytidine induce conversion of somatic cells into tissue-regenerative multipotent stem cells
Chandrakanthan, Vashe, Yeola, Avani, Kwan, Jair C., Oliver, Rema A., Qiao, Qiao, Kang, Young Chan, Zarzour, Peter, Beck, Dominik, Boelen, Lies, Unnikrishnan, Ashwin, Villanueva, Jeanette E., Nunez, Andrea C., Knezevic, Kathy, Palu, Cintia, Nasrallah, Rabab, Carnell, Michael, Macmillan, Alex, Whan, Renee, Yu, Yan, ... Pimanda, John E.. (2016). PDGF-AB and 5-Azacytidine induce conversion of somatic cells into tissue-regenerative multipotent stem cells. Proceedings of the National Academy of Sciences of USA. 113(16), pp. E2306 - E2315. https://doi.org/10.1073/pnas.1518244113
Defining the minimal factors required for erythropoiesis through direct lineage conversion
Capellera-Garcia, Sandra, Pulecio, Julian, Dhulipala, Kishori, Siva, Kavitha, Rayon-Estrada, Violeta, Singbrant, Sofie, Sommarin, Mikael N. E., Walkley, Carl R., Soneji, Shamit, Karlsson, Göran, Raya, Ángel, Sankaran, Vijay G. and Flygare, Johan. (2016). Defining the minimal factors required for erythropoiesis through direct lineage conversion. Cell Reports. 15(11), pp. 2550 - 2562. https://doi.org/10.1016/j.celrep.2016.05.027
Adenosine-to-inosine RNA editing by ADAR1 is essential for normal murine erythropoiesis
Liddicoat, Brian J., Hartner, Jochen C., Piskol, Robert, Ramaswami, Gokul, Chalk, Alistair M., Kingsley, Paul D., Sankaran, Vijay G., Wall, Meaghan, Purton, Louise E., Seeburg, Peter H., Palis, James, Orkin, Stuart H., Lu, Jun, Li, Jin Billy and Walkley, Carl R.. (2016). Adenosine-to-inosine RNA editing by ADAR1 is essential for normal murine erythropoiesis. Experimental Hematology. 44(10), pp. 947 - 963. https://doi.org/10.1016/j.exphem.2016.06.250
Loss of ephrinB1 in osteogenic progenitor cells impedes endochondral ossification and compromises bone strength integrity during skeletal development
Nguyen, Thao M., Arthur, Agnieszka, Paton, Sharon, Hemming, Sarah, Panagopoulos, Romana, Codrington, John D., Walkley, Carl R., Zannettino, Andrew C. W. and Gronthos, Stan. (2016). Loss of ephrinB1 in osteogenic progenitor cells impedes endochondral ossification and compromises bone strength integrity during skeletal development. Bone. 93, pp. 12 - 21. https://doi.org/10.1016/j.bone.2016.09.009
Increased miR-155-5p and reduced miR-148a-3p contribute to the suppression of osteosarcoma cell death
Bhattacharya, S., Chalk, Alistair M., Ng, A. J. M., Martin, T. John, Zannettino, Andrew C. W., Purton, L. E., Lu, J., Baker, E. K. and Walkley, Carl R.. (2016). Increased miR-155-5p and reduced miR-148a-3p contribute to the suppression of osteosarcoma cell death. Oncogene. 35(40), pp. 5282 - 5294. https://doi.org/10.1038/onc.2016.68
The transcription factor ASCIZ and its target DYNLL1 are essential for the development and expansion of MYC-driven B cell lymphoma
Wong, David M., Li, ngli Li, Jurado, Sabine, King, Ashleigh, Bamford, Rebecca, Wall, Meaghan, Walia, Mannu K., Kelly, Gemma L., Walkley, Carl R., Tarlinton, David M., Strasser, Andreas and Heierhorst, Jörg. (2016). The transcription factor ASCIZ and its target DYNLL1 are essential for the development and expansion of MYC-driven B cell lymphoma. Cell Reports. 14(6), pp. 1488 - 1499. https://doi.org/10.1016/j.celrep.2016.01.012
The role of RNA editing by ADAR1 in prevention of innate immune sensing of self-RNA
Heraud-Farlow, Jacki E. and Walkley, Carl R.. (2016). The role of RNA editing by ADAR1 in prevention of innate immune sensing of self-RNA. Journal of Molecular Medicine. 94(10), pp. 1095 - 1102. https://doi.org/10.1007/s00109-016-1416-1
Activation of PTHrP-cAMP-CREB1 signaling following p53 loss is essential for osteosarcoma initiation and maintenance
Walia, Mannu K., Ho, Patricia M. W., Taylor, Scott, Ng, Alvin J. M., Gupte, Ankita, Chalk, Alistair M., Zannettino, Andrew C. W., Martin, T. John and Walkley, Carl R.. (2016). Activation of PTHrP-cAMP-CREB1 signaling following p53 loss is essential for osteosarcoma initiation and maintenance. eLife. 5(April), pp. 1 - 31. https://doi.org/10.7554/eLife.13446
IAP antagonists sensitize murine osteosarcoma cells to killing by TNFα
Shekhar, Tanmay M., Miles, Mark A., Gupte, Ankita, Taylor, Scott, Tascone, Brianna, Walkley, Carl R. and Hawkins, Christine J.. (2016). IAP antagonists sensitize murine osteosarcoma cells to killing by TNFα. Oncotarget. 7(23), pp. 33866 - 33886. https://doi.org/10.18632/oncotarget.8980
Systematic screening identifies dual PI3K and mTOR inhibition as a conserved therapeutic vulnerability in osteosarcoma
Gupte, Ankita, Baker, E. K., Wan, Soo-San, Stewart, Elizabeth, Loh, Amos, Shelat, Anang A., Gould, Cathryn M., Chalk, Alistair M., Taylor, Scott, Lackovic, Kurt, Karlström, Åsa, Mutsaers, Anthony J., Desai, Jayesh, Madhamshettiwar, Piyush B., Zannettino, Andrew C. W., Burns, Christopher J., Huang, David C. S., Dyer, Michael A., Simpson, Kaylene J. and Walkley, Carl. (2015). Systematic screening identifies dual PI3K and mTOR inhibition as a conserved therapeutic vulnerability in osteosarcoma. Clinical Cancer Research. 21(14), pp. 3216 - 3229. https://doi.org/10.1158/1078-0432.CCR-14-3026
Wnt inhibitory factor 1 (WIF1) is a marker of osteoblastic differentiation stage and is not silenced by DNA methylation in osteosarcoma
Baker, Emma K., Taylor, Scott, Gupte, Ankita, Chalk, Alistair M., Bhattacharya, Shreya, Green, Alanna C., Martin, T. John, Strbenac, Dario, Robinson, Mark D., Purton, Louise E. and Walkley, Carl R.. (2015). Wnt inhibitory factor 1 (WIF1) is a marker of osteoblastic differentiation stage and is not silenced by DNA methylation in osteosarcoma. Bone. 73, pp. 223 - 232. https://doi.org/10.1016/j.bone.2014.12.063
Src family kinases and their role in hematological malignancies
Ku, Matthew, Wall, Meaghan, MacKinnon, Ruth N., Walkley, Carl R., Purton, Louise E., Tam, Constantine, Izon, David, Campbell, Lynda, Cheng, Heung-Chin and Nandurkar, Harshal. (2015). Src family kinases and their role in hematological malignancies. Leukemia and Lymphoma. 56(3), pp. 577 - 586. https://doi.org/10.3109/10428194.2014.907897
HIF-1α is required for hematopoietic stem cell mobilization and 4-prolyl hydroxylase inhibitors enhance mobilization by stabilizing HIF-1α
Forristal, C. E., Nowlan, B., Jacobsen, R. N., Barbier, V., Walkinshaw, G., Walkley, Carl, Winkler, I. G. and Levesque, J. P.. (2015). HIF-1α is required for hematopoietic stem cell mobilization and 4-prolyl hydroxylase inhibitors enhance mobilization by stabilizing HIF-1α. Leukemia. 29(6), pp. 1366 - 1378. https://doi.org/10.1038/leu.2015.8
The DNA Helicase Recql4 is required for normal osteoblast expansion and osteosarcoma formation
Ng, A. J. M., Walia, Mannu K., Smeets, Monique F., Mutsaers, Anthony J., Sims, Natalie A., Purton, L. E., Walsh, Nicole C., Martin, T. John and Walkley, Carl. (2015). The DNA Helicase Recql4 is required for normal osteoblast expansion and osteosarcoma formation. PLoS Genetics. 11(4), pp. 1 - 25. https://doi.org/10.1371/journal.pgen.1005160
BET inhibitors induce apoptosis through a MYC independent mechanism and synergise with CDK inhibitors to kill osteosarcoma cells
Baker, E. K., Taylor, Scott, Gupte, Ankita, Sharp, Phillip P., Walia, Mannu K., Walsh, Nicole C., Zannettino, Andrew C. W., Chalk, Alistair M., Burns, Christopher J. and Walkley, Carl. (2015). BET inhibitors induce apoptosis through a MYC independent mechanism and synergise with CDK inhibitors to kill osteosarcoma cells. Scientific Reports. 5, pp. 1 - 14. https://doi.org/10.1038/srep10120
RNA editing by ADAR1 prevents MDA5 sensing of endogenous dsRNA as nonself
Liddicoat, Brian J., Piskol, Robert, Chalk, Alistair M., Ramaswami, Gokul, Higuchi, Miyoko, Hartner, Jochen C., Li, Jin Billy, Seeburg, Peter H. and Walkley, Carl. (2015). RNA editing by ADAR1 prevents MDA5 sensing of endogenous dsRNA as nonself. Science. 349(6252), pp. 1115 - 1120. https://doi.org/10.1126/science.aac7049
Knockdown of PTHR1 in osteosarcoma cells decreases invasion and growth and increases tumor differentiation in vivo
Ho, P. W. M., Goradia, A., Russell, M. R., Chalk, Alistair M., Milley, K. M., Baker, E. K., Danks, J. A., Slavin, John, Walia, Mannu K., Crimeen-Irwin, B., Dickins, R. A., Martin, T. John and Walkley, Carl. (2015). Knockdown of PTHR1 in osteosarcoma cells decreases invasion and growth and increases tumor differentiation in vivo. Oncogene. 34(22), pp. 2922 - 2933. https://doi.org/10.1038/onc.2014.217
RARγ is a negative regulator of osteoclastogenesis
Green, Alanna C., Poulton, Ingrid J., Vrahnas, Christina, Häusler, Karl D., Walkley, Carl, Wu, Joy Y., Martin, T. John, Gillespie, Matthew T., Chandraratna, Roshantha A. S., Quinn, Julian M. W., Sims, Natalie A. and Purton, L. E.. (2015). RARγ is a negative regulator of osteoclastogenesis. The Journal of Steroid Biochemistry and Molecular Biology. 150, pp. 46 - 53. https://doi.org/10.1016/j.jsbmb.2015.03.005
Brief report: The differential roles of mTORC1 and mTORC2 in mesenchymal stem cell differentiation
Martin, Sally K., Fitter, Stephen, Dutta, Ankit K., Matthews, Mary P., Walkley, Carl, Hall, Michael N., Ruegg, Markus A., Gronthos, Stan and Zannettino, Andrew C. W.. (2015). Brief report: The differential roles of mTORC1 and mTORC2 in mesenchymal stem cell differentiation. Stem Cells. 33(4), pp. 1359 - 1365. https://doi.org/10.1002/stem.1931
Ciliary neurotrophic factor has intrinsic and extrinsic roles in regulating B cell differentiation and bone structure
Askmyr, Maria, White, Kirby E., Jovic, Tanja, King, Hannah A., Quach, Julie M., Maluenda, Ana C., Baker, E. K., Smeets, Monique F., Walkley, Carl and Purton, L. E.. (2015). Ciliary neurotrophic factor has intrinsic and extrinsic roles in regulating B cell differentiation and bone structure. Scientific Reports. 5, pp. 1 - 13. https://doi.org/10.1038/srep15529
PTHrP, its receptor, and protein kinase A activation in osteosarcoma
Walkley, Carl, Walia, Mannu K., Ho, P.W.M. and Martin, T. J.. (2014). PTHrP, its receptor, and protein kinase A activation in osteosarcoma. Molecular & Cellular Oncology. 1(4), pp. 1 - 3. https://doi.org/10.4161/23723548.2014.965624
Gene expression profiling to define the cell intrinsic role of the SKI proto-oncogene in hematopoiesis and myeloid neoplsms
Chalk, Alistair M., Liddicoat, Brian J., Walkley, Carl and Singbrant, Sofie. (2014). Gene expression profiling to define the cell intrinsic role of the SKI proto-oncogene in hematopoiesis and myeloid neoplsms. Genomics Data. 2, pp. 189 - 191. https://doi.org/10.1016/j.gdata.2014.06.022
The SKI proto-oncogene enhances the in vivo repopulation of hematopoietic stem cells and causes myeloproliferative disease
Singbrant, Sofie, Wall, Meaghan, Moody, Jennifer, Karlsson, Göran, Chalk, Alistair M., Liddicoat, Brian J., Russell, Megan R., Walkley, Carl R. and Karlsson, Stefan. (2014). The SKI proto-oncogene enhances the in vivo repopulation of hematopoietic stem cells and causes myeloproliferative disease. Haematologica. 99(4), pp. 647 - 655. https://doi.org/10.3324/haematol.2013.093971
The Rothmund-Thomson syndrome helicase RECQL4 is essential for hematopoiesis
Smeets, Monique F., DeLuca, Elisabetta, Wall, Meaghan, Quach, Julie M., Chalk, Alistair M., Deans, Andrew J., Heierhorst, Jörg, Purton, Louise E., Izon, David J. and Walkley, Carl R.. (2014). The Rothmund-Thomson syndrome helicase RECQL4 is essential for hematopoiesis. Journal of Clinical Investigation. 124(8), pp. 3551 - 3565. https://doi.org/10.1172/JCI75334
Cells of origin in osteosarcoma: Mesenchymal stem cells or osteoblast committed cells?
Mutsaers, Anthony J. and Walkley, Carl R.. (2014). Cells of origin in osteosarcoma: Mesenchymal stem cells or osteoblast committed cells? Bone. 62, pp. 56 - 63. https://doi.org/10.1016/j.bone.2014.02.003
Immune response to rb1-regulated senescence limits radiation-Induced osteosarcoma formation
Kansara, Maya, Leong, Huei San, Lin, Dan Mei, Popkiss, Sophie, Pang, Puiyi, Garsed, Dale W., Walkley, Carl R., Cullinane, Carleen, Ellul, Jason, Haynes, Nicole M., Hicks, Rod, Kuijjer, Marieke L., Cleton-Jansen, Anne-Marie, Hinds, Philip W., Smyth, Mark J. and Thomas, David M.. (2013). Immune response to rb1-regulated senescence limits radiation-Induced osteosarcoma formation. Journal of Clinical Investigation. 123(12), pp. 5351 - 5360. https://doi.org/10.1172/JCI70559
Erythroid-extrinsic regulation of normal erythropoiesis by retinoic acid receptors
Dewamitta, Sita R., Joseph, Chacko, Purton, Louise E. and Walkley, Carl R.. (2013). Erythroid-extrinsic regulation of normal erythropoiesis by retinoic acid receptors. British Journal of Haematology. 164(2), pp. 280 - 285. https://doi.org/10.1111/bjh.12578
Modeling distinct osteosarcoma subtypes in vivo using Cre: Lox and lineage-restricted transgenic shRNA
Mutsaers, Anthony J., Ng, Alvin J. M., Baker, Emma K., Russell, Megan R., Chalk, Alistair M., Wall, Meaghan, Liddicoat, Brian J. J., Ho, Patricia W. M., Slavin, John L., Goradia, Ankita, Martin, T. John, Purton, Louise E., Dickins, Ross A. and Walkley, Carl R.. (2013). Modeling distinct osteosarcoma subtypes in vivo using Cre: Lox and lineage-restricted transgenic shRNA. Bone. 55(1), pp. 166 - 178. https://doi.org/10.1016/j.bone.2013.02.016
Darbepoietin-alfa has comparable erythropoietic stimulatory effects to recombinant erythropoietin whilst preserving the bone marrow microenvironment
Dewamitta, Sita R., Russell, Megan R., Nandurkar, Harshal and Walkley, Carl R.. (2013). Darbepoietin-alfa has comparable erythropoietic stimulatory effects to recombinant erythropoietin whilst preserving the bone marrow microenvironment. Haematologica. 98(5), pp. 686 - 690. https://doi.org/10.3324/haematol.2012.078709
Deciphering hematopoietic stem cells in their niches: A critical appraisal of genetic models, lineage tracing, and imaging strategies
Joseph, Chacko, Quach, Julie M., Walkley, Carl R., Lane, Steven W., Celso, Cristina Lo and Purton, Louise E.. (2013). Deciphering hematopoietic stem cells in their niches: A critical appraisal of genetic models, lineage tracing, and imaging strategies. Cell Stem Cell. 13(5), pp. 520 - 533. https://doi.org/10.1016/j.stem.2013.10.010
The zinc-finger protein ASCIZ regulates B cell development via DYNLL1 and Bim
Jurado, Sabine, Gleeson, Kimberly, O’Donnell, Kristy, Izon, David J., Walkley, Carl R., Strasser, Andreas, Tarlinton, David M. and Heierhorst, Jörg. (2012). The zinc-finger protein ASCIZ regulates B cell development via DYNLL1 and Bim. Journal of Experimental Medicine. 209(9), pp. 1629-1639. https://doi.org/10.1084/jem.20120785
Fak depletion in both hematopoietic and nonhematopoietic niche cells leads to hematopoietic stem cell expansion
Lu, Jiayun, Sun, Yan, Nombela-Arrieta, Cesar, Du, Karrie P., Park, Shin-Young, Chai, Li, Walkley, Carl, Luo, Hongbo R. and Silberstein, Leslie E.. (2012). Fak depletion in both hematopoietic and nonhematopoietic niche cells leads to hematopoietic stem cell expansion. Experimental Hematology. 40(4), pp. 307-317. https://doi.org/10.1016/j.exphem.2011.11.010
Erythropoietin couples erythropoiesis, B-lymphopoiesis, and bone homeostasis within the bone marrow microenvironment
Singbrant, Sofie, Russell, Megan R., Jovic, Tanja, Liddicoat, Brian, Izon, David J., Purton, Louise E., Sims, Natalie A., Martin, T. John, Sankaran, Vijay G. and Walkley, Carl R.. (2011). Erythropoietin couples erythropoiesis, B-lymphopoiesis, and bone homeostasis within the bone marrow microenvironment. Blood. 117(21), pp. 5631-5642. https://doi.org/10.1182/blood-2010-11-320564
Erythropoiesis, anemia and the bone marrow microenvironment
Walkley, Carl R.. (2011). Erythropoiesis, anemia and the bone marrow microenvironment. International Journal of Hematology. 93, pp. 10-13. https://doi.org/10.1007/s12185-010-0759-6
Defining the hematopoietic stem cell niche : The chicken and the egg conundrum
Singbrant, Sofie, Askmyr, Maria, Purton, Louise E. and Walkley, Carl R.. (2011). Defining the hematopoietic stem cell niche : The chicken and the egg conundrum. Journal of Cellular Biochemistry. 112(6), pp. 1486-1490. https://doi.org/10.1002/jcb.23085
Hematopoietic AMPK beta1 reduces mouse adipose tissue macrophage inflammation and insulin resistance in obesity
Galic, Sandra, Fullerton, Morgan, Schertzer, Jonathan, Sikkema, Sarah, Marcinko, Katarina, Walkley, Carl, Izon, David, Honeyman, Jane, Chen, Zhi-Ping, Van Denderen, Bryce, Kemp, Bruce and Steinberg, Gregory. (2011). Hematopoietic AMPK beta1 reduces mouse adipose tissue macrophage inflammation and insulin resistance in obesity. Journal of Clinical Investigation. 121(12), pp. 4903 - 4915. https://doi.org/10.1172/JCI58577
Hematopoietic AMPK Beta ß1 reduces mouse adipose tissue macrophage inflammation and insulin resistance in obesity
Galic, Sandra, Fullerton, Morgan D., Schertzer, Jonathan D., Sikkema, Sarah, Marcinko, Katarina, Walkley, Carl R., Izon, David, Honeyman, Jane, Chen, Zhi-Ping, van Denderen, Bryce J., Kemp, Bruce Ernest and Steinberg, Gregory R.. (2011). Hematopoietic AMPK Beta ß1 reduces mouse adipose tissue macrophage inflammation and insulin resistance in obesity. Journal of Clinical Investigation. 121(12), pp. 4903 - 4915. https://doi.org/10.1172/JCI58577