ETO2-GLIS2 Hijacks Transcriptional Complexes to Drive Cellular Identity and Self-Renewal in Pediatric Acute Megakaryoblastic Leukemia

Adam, 2015, Pioneer factors govern super-enhancer dynamics in stem cell plasticity and lineage choice, Nature, 521, 366, 10.1038/nature14289 Attanasio, 2007, Loss of GLIS2 causes nephronophthisis in humans and mice by increased apoptosis and fibrosis, Nat. Genet., 39, 1018, 10.1038/ng2072 Batta, 2014, Direct reprogramming of murine fibroblasts to hematopoietic progenitor cells, Cell Rep., 9, 1871, 10.1016/j.celrep.2014.11.002 Birger, 2013, Perturbation of fetal hematopoiesis in a mouse model of Down syndrome's transient myeloproliferative disorder, Blood, 122, 988, 10.1182/blood-2012-10-460998 Bourquin, 2006, Identification of distinct molecular phenotypes in acute megakaryoblastic leukemia by gene expression profiling, Proc. Natl. Acad. Sci. USA, 103, 3339, 10.1073/pnas.0511150103 Bresnick, 2012, Master regulatory GATA transcription factors: mechanistic principles and emerging links to hematologic malignancies, Nucleic Acids Res., 40, 5819, 10.1093/nar/gks281 Carmichael, 2012, Hematopoietic overexpression of the transcription factor Erg induces lymphoid and erythro-megakaryocytic leukemia, Proc. Natl. Acad. Sci. USA, 109, 15437, 10.1073/pnas.1213454109 Chyla, 2008, Deletion of Mtg16, a target of t(16;21), alters hematopoietic progenitor cell proliferation and lineage allocation, Mol. Cell Biol., 28, 6234, 10.1128/MCB.00404-08 Dawson, 2011, Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia, Nature, 478, 529, 10.1038/nature10509 de Rooij, 2017, Pediatric non-Down syndrome acute megakaryoblastic leukemia is characterized by distinct genomic subsets with varying outcomes, Nat. Genet., 10.1038/ng.3772 Dore, 2011, Transcription factor networks in erythroid cell and megakaryocyte development, Blood, 118, 231, 10.1182/blood-2011-04-285981 Filippakopoulos, 2010, Selective inhibition of BET bromodomains, Nature, 468, 1067, 10.1038/nature09504 Fischer, 2012, Myeloid translocation gene 16 is required for maintenance of haematopoietic stem cell quiescence, EMBO J., 31, 1494, 10.1038/emboj.2011.500 Groschel, 2014, A single oncogenic enhancer rearrangement causes concomitant EVI1 and GATA2 deregulation in leukemia, Cell, 157, 369, 10.1016/j.cell.2014.02.019 Gruber, 2012, An Inv(16)(p13.3q24.3)-encoded CBFA2T3-GLIS2 fusion protein defines an aggressive subtype of pediatric acute megakaryoblastic leukemia, Cancer Cell, 22, 683, 10.1016/j.ccr.2012.10.007 Hamlett, 2008, Characterization of megakaryocyte GATA1-interacting proteins: the corepressor ETO2 and GATA1 interact to regulate terminal megakaryocyte maturation, Blood, 112, 2738, 10.1182/blood-2008-03-146605 Hara, 2017, Prognostic impact of specific molecular profiles in pediatric acute megakaryoblastic leukemia in non-down syndrome, Genes Chromosomes Cancer, 10.1002/gcc.22444 Herranz, 2014, A NOTCH1-driven MYC enhancer promotes T cell development, transformation and acute lymphoblastic leukemia, Nat. Med., 20, 1130, 10.1038/nm.3665 Hunt, 2011, Mtg16/Eto2 contributes to murine T-cell development, Mol. Cell Biol., 31, 2544, 10.1128/MCB.01458-10 Knudsen, 2015, ERG promotes the maintenance of hematopoietic stem cells by restricting their differentiation, Genes Dev., 29, 1915, 10.1101/gad.268409.115 Leung, 2013, Uncoupling VEGFA functions in arteriogenesis and hematopoietic stem cell specification, Dev. Cell, 24, 144, 10.1016/j.devcel.2012.12.004 Lichti-Kaiser, 2012, Gli-similar proteins: their mechanisms of action, physiological functions, and roles in disease, Vitam Horm., 88, 141, 10.1016/B978-0-12-394622-5.00007-9 Liu, 2006, The tetramer structure of the Nervy homology two domain, NHR2, is critical for AML1/ETO's activity, Cancer Cell, 9, 249, 10.1016/j.ccr.2006.03.012 Loven, 2013, Selective inhibition of tumor oncogenes by disruption of super-enhancers, Cell, 153, 320, 10.1016/j.cell.2013.03.036 Lutterbach, 1998, The MYND motif is required for repression of basal transcription from the multidrug resistance 1 promoter by the t(8;21) fusion protein, Mol. Cell Biol., 18, 3604, 10.1128/MCB.18.6.3604 Maekawa, 2011, Direct reprogramming of somatic cells is promoted by maternal transcription factor Glis1, Nature, 474, 225, 10.1038/nature10106 Malinge, 2012, Increased dosage of the chromosome 21 ortholog Dyrk1a promotes megakaryoblastic leukemia in a murine model of Down syndrome, J. Clin. Invest., 122, 948, 10.1172/JCI60455 Marcucci, 2005, Overexpression of the ETS-related gene, ERG, predicts a worse outcome in acute myeloid leukemia with normal karyotype: a Cancer and Leukemia Group B study, J. Clin. Oncol., 23, 9234, 10.1200/JCO.2005.03.6137 Margolin, 2006, ARACNE: an algorithm for the reconstruction of gene regulatory networks in a mammalian cellular context, BMC Bioinformatics, 7, S7, 10.1186/1471-2105-7-S1-S7 Masetti, 2017, Hh/Gli antagonist in acute myeloid leukemia with CBFA2T3-GLIS2 fusion gene, J. Hematol. Oncol., 10, 26, 10.1186/s13045-017-0396-0 Mazumdar, 2015, Leukemia-associated cohesin mutants dominantly enforce stem cell programs and impair human hematopoietic progenitor differentiation, Cell Stem Cell, 17, 675, 10.1016/j.stem.2015.09.017 Meier, 2006, Novel binding partners of Ldb1 are required for haematopoietic development, Development, 133, 4913, 10.1242/dev.02656 Northcott, 2014, Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma, Nature, 511, 428, 10.1038/nature13379 Novershtern, 2011, Densely interconnected transcriptional circuits control cell states in human hematopoiesis, Cell, 144, 296, 10.1016/j.cell.2011.01.004 Pells, 2015, Novel human embryonic stem cell regulators identified by conserved and distinct CpG island methylation state, PLoS One, 10, e0131102, 10.1371/journal.pone.0131102 Rainis, 2005, The proto-oncogene ERG in megakaryoblastic leukemias, Cancer Res., 65, 7596, 10.1158/0008-5472.CAN-05-0147 Rockova, 2011, Risk stratification of intermediate-risk acute myeloid leukemia: integrative analysis of a multitude of gene mutation and gene expression markers, Blood, 118, 1069, 10.1182/blood-2011-02-334748 Salek-Ardakani, 2009, ERG is a megakaryocytic oncogene, Cancer Res., 69, 4665, 10.1158/0008-5472.CAN-09-0075 Soler, 2010, The genome-wide dynamics of the binding of Ldb1 complexes during erythroid differentiation, Genes Dev., 24, 277, 10.1101/gad.551810 Stachura, 2006, Early block to erythromegakaryocytic development conferred by loss of transcription factor GATA-1, Blood, 107, 87, 10.1182/blood-2005-07-2740 Stadhouders, 2015, Control of developmentally primed erythroid genes by combinatorial co-repressor actions, Nat. Commun., 6, 8893, 10.1038/ncomms9893 Stankiewicz, 2009, ETS2 and ERG promote megakaryopoiesis and synergize with alterations in GATA-1 to immortalize hematopoietic progenitor cells, Blood, 113, 3337, 10.1182/blood-2008-08-174813 Stavropoulou, 2016, MLL-AF9 expression in hematopoietic stem cells drives a highly invasive AML expressing EMT-related genes linked to poor outcome, Cancer Cell, 30, 43, 10.1016/j.ccell.2016.05.011 Sun, 2013, A stable transcription factor complex nucleated by oligomeric AML1-ETO controls leukaemogenesis, Nature, 500, 93, 10.1038/nature12287 Thiollier, 2012, Characterization of novel genomic alterations and therapeutic approaches using acute megakaryoblastic leukemia xenograft models, J. Exp. Med., 209, 2017, 10.1084/jem.20121343 Tijssen, 2011, Genome-wide analysis of simultaneous GATA1/2, RUNX1, FLI1, and SCL binding in megakaryocytes identifies hematopoietic regulators, Dev. Cell, 20, 597, 10.1016/j.devcel.2011.04.008 van Riel, 2012, A novel complex, RUNX1-MYEF2, represses hematopoietic genes in erythroid cells, Mol. Cell Biol., 32, 3814, 10.1128/MCB.05938-11 Vasanth, 2011, Identification of nuclear localization, DNA binding, and transactivating mechanisms of Kruppel-like zinc finger protein Gli-similar 2 (Glis2), J. Biol. Chem., 286, 4749, 10.1074/jbc.M110.165951 Wechsler, 2002, Acquired mutations in GATA1 in the megakaryoblastic leukemia of Down syndrome, Nat. Genet., 32, 148, 10.1038/ng955 Whyte, 2013, Master transcription factors and mediator establish super-enhancers at key cell identity genes, Cell, 153, 307, 10.1016/j.cell.2013.03.035 Wichmann, 2007, Targeting the oligomerization domain of ETO interferes with RUNX1/ETO oncogenic activity in t(8;21)-positive leukemic cells, Cancer Res., 67, 2280, 10.1158/0008-5472.CAN-06-3360 Wichmann, 2010, Dimer-tetramer transition controls RUNX1/ETO leukemogenic activity, Blood, 116, 603, 10.1182/blood-2009-10-248047 Yan, 2009, RUNX1/AML1 DNA-binding domain and ETO/MTG8 NHR2-dimerization domain are critical to AML1-ETO9a leukemogenesis, Blood, 113, 883, 10.1182/blood-2008-04-153742 Yoshioka, 2013, Efficient generation of human iPSCs by a synthetic self-replicative RNA, Cell Stem Cell, 13, 246, 10.1016/j.stem.2013.06.001