The transcription factor ASCIZ and its target DYNLL1 are essential for the development and expansion of MYC-driven B cell lymphoma

Journal article

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
AuthorsWong, 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
Abstract

How MYC promotes the development of cancer remains to be fully understood. Here, we report that the Zn2+-finger transcription factor ASCIZ (ATMIN, ZNF822) synergizes with MYC to activate the expression of dynein light chain (DYNLL1, LC8) in the murine Eμ-Myc model of lymphoma. Deletion of Asciz or Dynll1 prevented the abnormal expansion of pre-B cells in pre-cancerous Eμ-Myc mice and potentiated the pro-apoptotic activity of MYC in pre-leukemic immature B cells. Constitutive loss of Asciz or Dynll1 delayed lymphoma development in Eμ-Myc mice, and induced deletion of Asciz in established lymphomas extended the survival of tumor-bearing mice. We propose that ASCIZ-dependent upregulation of DYNLL1 levels is essential for the development and expansion of MYC-driven lymphomas by enabling the survival of pre-neoplastic and malignant cells.

Year2016
JournalCell Reports
Journal citation14 (6), pp. 1488 - 1499
PublisherElsevier
ISSN2211-1247
Digital Object Identifier (DOI)https://doi.org/10.1016/j.celrep.2016.01.012
Scopus EID2-s2.0-84958650086
Open accessOpen access
Page range1488 - 1499
Research GroupMary MacKillop Institute for Health Research
Publisher's version
Place of publicationNetherlands
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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