Genomes and Genes
core binding factor alpha 2 subunit
Summary: A transcription factor that dimerizes with the cofactor CORE BINDING FACTOR BETA SUBUNIT to form core binding factor. It contains a highly conserved DNA-binding domain known as the runt domain. Runx1 is frequently mutated in human LEUKEMIAS.
- Ginhoux F, Merad M. [Microglia arise from extra-embryonic yolk sac primitive progenitors]. Med Sci (Paris). 2011;27:719-24 pubmed publisher..These results identify microglia as an ontogenically distinct population in the mononuclear phagocyte system and have implications for the use of embryonically-derived microglial progenitors for the treatment of various brain disorders...
- Wang L, Gural A, Sun X, Zhao X, Perna F, Huang G, et al. The leukemogenicity of AML1-ETO is dependent on site-specific lysine acetylation. Science. 2011;333:765-9 pubmed publisher..Inhibition of p300 abrogates the acetylation of AML1-ETO and impairs its ability to promote leukemic transformation. Thus, lysine acetyltransferases represent a potential therapeutic target in AML. ..
- Yu M, Mazor T, Huang H, Huang H, Kathrein K, Woo A, et al. Direct recruitment of polycomb repressive complex 1 to chromatin by core binding transcription factors. Mol Cell. 2012;45:330-43 pubmed publisher..Genetic depletion of Runx1 results in reduced Ring1b binding at these sites in vivo. These findings provide evidence for site-specific PRC1 chromatin recruitment by core binding transcription factors in mammalian cells. ..
- Shia W, Okumura A, Yan M, Sarkeshik A, Lo M, Matsuura S, et al. PRMT1 interacts with AML1-ETO to promote its transcriptional activation and progenitor cell proliferative potential. Blood. 2012;119:4953-62 pubmed publisher..More importantly, knockdown of PRMT1 suppresses the self-renewal capability of AE9a, suggesting a potential role of PRMT1 in regulating leukemia development. ..
- Giguère A, Hébert J. CLCA2, a novel RUNX1 partner gene in a therapy-related leukemia with t(1;21)(p22;q22). Cancer Genet Cytogenet. 2010;202:94-100 pubmed publisher..The RUNX1-CLCA2 fusion is another example of out-of-frame fusion generating truncated RUNX1 isoforms that represent a recurrent molecular mechanism in RUNX1-related leukemias. ..
- Mangolini M, de Boer J, Walf Vorderwülbecke V, Pieters R, den Boer M, Williams O. STAT3 mediates oncogenic addiction to TEL-AML1 in t(12;21) acute lymphoblastic leukemia. Blood. 2013;122:542-9 pubmed publisher..Thus, STAT3 inhibition represents a promising possible therapeutic strategy for the treatment of TEL-AML1 leukemia. ..
- Zapotocky M, Mejstrikova E, Smetana K, Stary J, Trka J, Starkova J. Valproic acid triggers differentiation and apoptosis in AML1/ETO-positive leukemic cells specifically. Cancer Lett. 2012;319:144-153 pubmed publisher..Our data suggest that AML1/ETO-positive patients might derive the greatest benefit from VPA treatment. ..
- Kuster L, Grausenburger R, Fuka G, Kaindl U, Krapf G, Inthal A, et al. ETV6/RUNX1-positive relapses evolve from an ancestral clone and frequently acquire deletions of genes implicated in glucocorticoid signaling. Blood. 2011;117:2658-67 pubmed publisher..These findings implicate glucocorticoid-associated drug resistance in ETV6/RUNX1-positive relapse pathogenesis and therefore might help to guide future therapies. ..
- Tanaka Y, Hayashi M, Kubota Y, Nagai H, Sheng G, Nishikawa S, et al. Early ontogenic origin of the hematopoietic stem cell lineage. Proc Natl Acad Sci U S A. 2012;109:4515-20 pubmed publisher..Our data also suggest that other anatomical sites that have been proposed to be sources of the definitive hematopoietic hierarchy are unlikely to play a substantial role in de novo blood generation. ..
- Schnittger S, Dicker F, Kern W, Wendland N, Sundermann J, Alpermann T, et al. RUNX1 mutations are frequent in de novo AML with noncomplex karyotype and confer an unfavorable prognosis. Blood. 2011;117:2348-57 pubmed publisher..Multivariate analysis showed independent prognostic relevance for overall survival for RUNX1mut (P = .029), FLT3-ITD (P = .003), age (P < .001), and white blood cell count (P < .002). ..
- Zagami C, Stifani S. Molecular characterization of the mouse superior lateral parabrachial nucleus through expression of the transcription factor Runx1. PLoS ONE. 2010;5:e13944 pubmed publisher..Based on the anatomical and molecular characteristics of the Runx1-expressing cells in the rostral hindbrain, we propose that Runx1 expression in this region of the mouse brain defines the superior lateral parabrachial nucleus. ..
- Zusso M, Methot L, Lo R, Greenhalgh A, David S, Stifani S. Regulation of postnatal forebrain amoeboid microglial cell proliferation and development by the transcription factor Runx1. J Neurosci. 2012;32:11285-98 pubmed publisher..These findings provide insight into the regulation of postnatal microglia activation and maturation to the ramified state and have implications for microglia biology in the developing and injured brain. ..
- Montero Ruiz O, Alcántara Ortigoza M, Betancourt M, Juárez Velázquez R, González Márquez H, Pérez Vera P. Expression of RUNX1 isoforms and its target gene BLK in childhood acute lymphoblastic leukemia. Leuk Res. 2012;36:1105-11 pubmed publisher..Only expression of the total RUNT domain-containing isoforms and BLK presented positive correlation. Results suggest a more complex role of RUNX1 in leukemogenesis than the proposed antagonism between the isoforms. ..
- Chen M, Li Y, De Obaldia M, Yang Q, Yzaguirre A, Yamada Inagawa T, et al. Erythroid/myeloid progenitors and hematopoietic stem cells originate from distinct populations of endothelial cells. Cell Stem Cell. 2011;9:541-52 pubmed publisher..The data indicate that EMPs and HSCs differentiate from distinct populations of hemogenic endothelial cells, with Ly6a expression specifically marking the HSC-generating hemogenic endothelium...
- Duque Afonso J, Yalcin A, Berg T, Abdelkarim M, Heidenreich O, Lubbert M. The HDAC class I-specific inhibitor entinostat (MS-275) effectively relieves epigenetic silencing of the LAT2 gene mediated by AML1/ETO. Oncogene. 2011;30:3062-72 pubmed publisher..In conclusion, several repressive histone modifications mark the LAT2 gene in the presence of AML1/ETO, and LAT2 gene derepression is achieved by pharmacological inhibition of HDACs. ..
- Giguère A, Hébert J. Microhomologies and topoisomerase II consensus sequences identified near the breakpoint junctions of the recurrent t(7;21)(p22;q22) translocation in acute myeloid leukemia. Genes Chromosomes Cancer. 2011;50:228-38 pubmed publisher..Moreover, presence of the complete catalytic USP site in the putative chimeric proteins and the upregulated expression of USP42 suggest a role of the deubiquitinating enzyme in the pathogenesis of this leukemia. ..
- Scheitz C, Lee T, McDermitt D, Tumbar T. Defining a tissue stem cell-driven Runx1/Stat3 signalling axis in epithelial cancer. EMBO J. 2012;31:4124-39 pubmed publisher..Thus, Runx1 is a broader epithelial SC and cancer factor than previously recognized, and qualifies as an attractive potential target for both prevention and therapy of several epithelial cancers. ..
- Gessner A, Thomas M, Castro P, Büchler L, Scholz A, Brummendorf T, et al. Leukemic fusion genes MLL/AF4 and AML1/MTG8 support leukemic self-renewal by controlling expression of the telomerase subunit TERT. Leukemia. 2010;24:1751-9 pubmed publisher..We thus present findings that show a mechanistic link between leukemic fusion proteins, essential for development and maintenance of leukemia, and telomerase, a key element of both normal and malignant self-renewal. ..
- Diakos C, Zhong S, Xiao Y, Zhou M, Vasconcelos G, Krapf G, et al. TEL-AML1 regulation of survivin and apoptosis via miRNA-494 and miRNA-320a. Blood. 2010;116:4885-93 pubmed publisher..In summary our data suggest that TEL-AML1 might exert its antiapoptotic action at least in part by suppressing miRNA-494 and miRNA-320a, lowering their expression causing enhanced survivin expression. ..
- Kawashima N, Shimada A, Taketani T, Hayashi Y, Yoshida N, Matsumoto K, et al. Childhood acute myeloid leukemia with bone marrow eosinophilia caused by t(16;21)(q24;q22). Int J Hematol. 2012;95:577-80 pubmed publisher..He received chemotherapy and survived for more than 70 months without transplantation. We speculated that pediatric AML with t(16;21)(q24;q22) showed favorable prognosis, as with t(8;21)(q22;q22). ..
- Iacovino M, Chong D, Szatmari I, Hartweck L, Rux D, Caprioli A, et al. HoxA3 is an apical regulator of haemogenic endothelium. Nat Cell Biol. 2011;13:72-8 pubmed publisher..These results suggest both why a frank endothelium does not precede haematopoiesis in the yolk sac, and why haematopoietic stem cell generation requires Runx1 expression only in endothelial cells. ..
- Martens J, Mandoli A, Simmer F, Wierenga B, Saeed S, Singh A, et al. ERG and FLI1 binding sites demarcate targets for aberrant epigenetic regulation by AML1-ETO in acute myeloid leukemia. Blood. 2012;120:4038-48 pubmed publisher..Together, these results highlight the dual importance of ETS factors in t(8;21) leukemogenesis, both as transcriptional regulators of the oncofusion protein itself as well as proteins that facilitate AML1-ETO binding. ..
- Nishimoto N, Arai S, Ichikawa M, Nakagawa M, Goyama S, Kumano K, et al. Loss of AML1/Runx1 accelerates the development of MLL-ENL leukemia through down-regulation of p19ARF. Blood. 2011;118:2541-50 pubmed publisher..These results provide a new insight into a role for AML1 in the progression of leukemia. ..
- Nakagawa M, Shimabe M, Watanabe Okochi N, Arai S, Yoshimi A, Shinohara A, et al. AML1/RUNX1 functions as a cytoplasmic attenuator of NF-?B signaling in the repression of myeloid tumors. Blood. 2011;118:6626-37 pubmed publisher..These findings reveal a novel role for AML1 as a cytoplasmic attenuator of NF-?B signaling and indicate that NF-?B signaling is one of the promising therapeutic targets of hematologic malignancies with AML1 abnormality. ..
- Tsuzuki S, Seto M. Expansion of functionally defined mouse hematopoietic stem and progenitor cells by a short isoform of RUNX1/AML1. Blood. 2012;119:727-35 pubmed publisher..Therefore, the abilities of AML1a may have implications for HSC transplantation and transfusion medicine, given that the effects also can be obtained by cell-penetrating AML1a protein. ..
- Levantini E, Lee S, Radomska H, Hetherington C, Alberich Jorda M, Amabile G, et al. RUNX1 regulates the CD34 gene in haematopoietic stem cells by mediating interactions with a distal regulatory element. EMBO J. 2011;30:4059-70 pubmed publisher..Overall, our in vivo data provide novel evidence about the role of RUNX1 in mediating interactions between distal and proximal elements of the HSC gene CD34. ..
- Boyapati A, Ren B, Zhang D. SERPINB13 is a novel RUNX1 target gene. Biochem Biophys Res Commun. 2011;411:115-20 pubmed publisher..These data demonstrate that RUNX1 is an important regulator of SERPINB13 and cathepsin K activity. ..
- Mangan J, Speck N. RUNX1 mutations in clonal myeloid disorders: from conventional cytogenetics to next generation sequencing, a story 40 years in the making. Crit Rev Oncog. 2011;16:77-91 pubmed
- Osorio K, Lilja K, Tumbar T. Runx1 modulates adult hair follicle stem cell emergence and maintenance from distinct embryonic skin compartments. J Cell Biol. 2011;193:235-50 pubmed publisher..Thus, a master regulator of hematopoiesis also controls HFSC emergence and maintenance via modulation of bidirectional cross talking between nascent stem cells and their niche. ..
- Kohlmann A, Grossmann V, Klein H, Schindela S, Weiss T, Kazak B, et al. Next-generation sequencing technology reveals a characteristic pattern of molecular mutations in 72.8% of chronic myelomonocytic leukemia by detecting frequent alterations in TET2, CBL, RAS, and RUNX1. J Clin Oncol. 2010;28:3858-65 pubmed publisher..Here, NGS screening has been demonstrated to support a comprehensive characterization of the molecular background in CMML. A pattern of molecular mutations translates into different biologic and prognostic categories of CMML. ..
- Zhao L, Wang Y, Li G, Ma L, Xiong S, Weng X, et al. Functional features of RUNX1 mutants in acute transformation of chronic myeloid leukemia and their contribution to inducing murine full-blown leukemia. Blood. 2012;119:2873-82 pubmed publisher..These results suggest that RUNX1 abnormalities may promote acute myeloid leukemic transformation in a subset of CML patients...
- Matsuura S, Komeno Y, Stevenson K, Biggs J, Lam K, Tang T, et al. Expression of the runt homology domain of RUNX1 disrupts homeostasis of hematopoietic stem cells and induces progression to myelodysplastic syndrome. Blood. 2012;120:4028-37 pubmed publisher..The data presented here provide insights into the mechanisms of development of MDS in HSCs by C-terminal mutations of RUNX1. ..
- Cai X, Gaudet J, Mangan J, Chen M, De Obaldia M, Oo Z, et al. Runx1 loss minimally impacts long-term hematopoietic stem cells. PLoS ONE. 2011;6:e28430 pubmed publisher..Finally, we identify genes and pathways, including the cell cycle and p53 pathways that are dysregulated in Runx1 deficient HSCs. ..
- Egawa T, Littman D. Transcription factor AP4 modulates reversible and epigenetic silencing of the Cd4 gene. Proc Natl Acad Sci U S A. 2011;108:14873-8 pubmed publisher..Our results suggest that AP4 contributes to Cd4 silencing both in DN and CD8(+) T cells by enforcing checkpoints for appropriate timing of CD4 expression and its epigenetic silencing. ..
- Fuka G, Kantner H, Grausenburger R, Inthal A, Bauer E, Krapf G, et al. Silencing of ETV6/RUNX1 abrogates PI3K/AKT/mTOR signaling and impairs reconstitution of leukemia in xenografts. Leukemia. 2012;26:927-33 pubmed publisher..Importantly, these results provide a first rationale and justification for targeting the fusion gene and the PI3K/AKT/mTOR pathway therapeutically. ..
- Huang G, Zhao X, Wang L, Elf S, Xu H, Zhao X, et al. The ability of MLL to bind RUNX1 and methylate H3K4 at PU.1 regulatory regions is impaired by MDS/AML-associated RUNX1/AML1 mutations. Blood. 2011;118:6544-52 pubmed publisher..1 regulatory regions, and decreased PU.1 expression. The interaction between MLL and AML1 provides a mechanism for the sequence-specific binding of MLL to DNA, and identifies RUNX1 target genes as potential effectors of MLL function. ..
- Kobayashi A, Senzaki K, Ozaki S, Yoshikawa M, Shiga T. Runx1 promotes neuronal differentiation in dorsal root ganglion. Mol Cell Neurosci. 2012;49:23-31 pubmed publisher..5. In summary, the present study suggests a novel function that Runx1 activates the neuronal differentiation of DRG cell subpopulation through the repression of Hes1 expression in early embryonic period. ..
- Torrano V, Procter J, Cardus P, Greaves M, Ford A. ETV6-RUNX1 promotes survival of early B lineage progenitor cells via a dysregulated erythropoietin receptor. Blood. 2011;118:4910-8 pubmed publisher..These data support the contention that ETV6-RUNX1 directly activates ectopic expression of a functional EPOR and provides cell survival signals that may contribute critically to persistence of covert premalignant clones in children. ..
- Gaidzik V, Bullinger L, Schlenk R, Zimmermann A, Röck J, Paschka P, et al. RUNX1 mutations in acute myeloid leukemia: results from a comprehensive genetic and clinical analysis from the AML study group. J Clin Oncol. 2011;29:1364-72 pubmed publisher..0001). AML with RUNX1 mutations are characterized by distinct genetic properties and are associated with resistance to therapy and inferior outcome. ..
- Fuka G, Kauer M, Kofler R, Haas O, Panzer Grümayer R. The leukemia-specific fusion gene ETV6/RUNX1 perturbs distinct key biological functions primarily by gene repression. PLoS ONE. 2011;6:e26348 pubmed publisher..Finally, these findings may also provide a valuable source of potentially attractive therapeutic targets. ..
- Slattery M, Lundgreen A, Herrick J, Caan B, Potter J, Wolff R. Associations between genetic variation in RUNX1, RUNX2, RUNX3, MAPK1 and eIF4E and riskof colon and rectal cancer: additional support for a TGF-?-signaling pathway. Carcinogenesis. 2011;32:318-26 pubmed publisher..47 (95% CI 1.58, 35.3). Although the associations need confirmation, the findings and their internal consistency underline the importance of genetic variation in these genes for the etiology of CRC. ..
- Nishimoto N, Imai Y, Ueda K, Nakagawa M, Shinohara A, Ichikawa M, et al. T cell acute lymphoblastic leukemia arising from familial platelet disorder. Int J Hematol. 2010;92:194-7 pubmed publisher..Taken together, t(1;7)(p34.1;q22) is thought to be one of the somatic second hits that predisposes FPD to acute leukemia with T cell phenotype. ..
- Pencovich N, Jaschek R, Tanay A, Groner Y. Dynamic combinatorial interactions of RUNX1 and cooperating partners regulates megakaryocytic differentiation in cell line models. Blood. 2011;117:e1-14 pubmed publisher..The findings suggest that in differentiating megakaryocytic cell lines, RUNX1 cooperates with GATA1, AP-1, and ETS to orchestrate cell-specific transcription programs through dynamic TF partnerships. ..
- Ginhoux F, Greter M, Leboeuf M, Nandi S, See P, Gokhan S, et al. Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science. 2010;330:841-5 pubmed publisher..These results identify microglia as an ontogenically distinct population in the mononuclear phagocyte system and have implications for the use of embryonically derived microglial progenitors for the treatment of various brain disorders...
- Gandemer V, Chevret S, Petit A, Vermylen C, Leblanc T, Michel G, et al. Excellent prognosis of late relapses of ETV6/RUNX1-positive childhood acute lymphoblastic leukemia: lessons from the FRALLE 93 protocol. Haematologica. 2012;97:1743-50 pubmed publisher..The duration of first complete remission may, therefore, be a guide to define the treatment strategy for patients with relapsed ETV6/RUNX1- positive leukemia. ..
- Ptasinska A, Assi S, Mannari D, James S, Williamson D, Dunne J, et al. Depletion of RUNX1/ETO in t(8;21) AML cells leads to genome-wide changes in chromatin structure and transcription factor binding. Leukemia. 2012;26:1829-41 pubmed publisher..This demonstrates that RUNX1/ETO represents a pivotal therapeutic target in AML. ..
- Wang Y, Zhao L, Wu C, Liu P, Shi L, Liang Y, et al. C-KIT mutation cooperates with full-length AML1-ETO to induce acute myeloid leukemia in mice. Proc Natl Acad Sci U S A. 2011;108:2450-5 pubmed publisher..Furthermore, dasatinib prolonged lifespan of mice bearing AE and HyC-KIT N822K-coexpressing leukemic cells and exerted synergic effects while combined with cytarabine, thus providing a potential therapeutic for t(8;21) leukemia. ..
- Swiers G, de Bruijn M, Speck N. Hematopoietic stem cell emergence in the conceptus and the role of Runx1. Int J Dev Biol. 2010;54:1151-63 pubmed publisher..Where relevant, we will include data obtained from other species and embryonic stem (ES) cell differentiation cultures...
- Abe A, Katsumi A, Kobayashi M, Okamoto A, Tokuda M, Kanie T, et al. A novel RUNX1-C11orf41 fusion gene in a case of acute myeloid leukemia with a t(11;21)(p14;q22). Cancer Genet. 2012;205:608-11 pubmed publisher..This suggested that the RUNX1 breakpoint was in intron 6 and had generated alternative fusion splice variants. A reciprocal C11orf41-RUNX1 fusion was not detected. Thus, we identified C11orf41 as a novel fusion partner of RUNX1 in AML. ..
- De Braekeleer E, Douet Guilbert N, Morel F, LE Bris M, Ferec C, de Braekeleer M. RUNX1 translocations and fusion genes in malignant hemopathies. Future Oncol. 2011;7:77-91 pubmed publisher..All the translocations that retain Runt homology domains but remove the transcription activation domain have a leukemogenic effect by acting as dominant negative inhibitors of wild-type RUNX1 in transcription activation. ..
- Tijssen M, Cvejic A, Joshi A, Hannah R, Ferreira R, Forrai A, et al. Genome-wide analysis of simultaneous GATA1/2, RUNX1, FLI1, and SCL binding in megakaryocytes identifies hematopoietic regulators. Dev Cell. 2011;20:597-609 pubmed publisher..Multifactor ChIP-Seq analysis in primary human cells coupled with a high-throughput in vivo perturbation screen therefore offers a powerful strategy to identify essential regulators of complex mammalian differentiation processes...
- Abdel Samad O, Liu Y, Yang F, Kramer I, Arber S, Ma Q. Characterization of two Runx1-dependent nociceptor differentiation programs necessary for inflammatory versus neuropathic pain. Mol Pain. 2010;6:45 pubmed publisher..These studies lend support to a transcription factor-based distinction of neuronal classes necessary for inflammatory versus neuropathic pain. ..
- Naoe Y, Setoguchi R, Akiyama K, Muroi S, Kuroda M, Hatam F, et al. Repression of interleukin-4 in T helper type 1 cells by Runx/Cbf beta binding to the Il4 silencer. J Exp Med. 2007;204:1749-55 pubmed..These results demonstrate critical roles of Runx complexes in regulating immune responses, at least in part, through the repression of the Il4 gene. ..
- Marshall L, Moore A, Ohki M, Kitabayashi I, Patterson D, Ornelles D. RUNX1 permits E4orf6-directed nuclear localization of the adenovirus E1B-55K protein and associates with centers of viral DNA and RNA synthesis. J Virol. 2008;82:6395-408 pubmed publisher..Subsequent studies will need to determine a functional consequence of the interaction between E4orf6, E1B-55K, and RUNX1. ..
- Liu Y, Yang F, Okuda T, Dong X, Zylka M, Chen C, et al. Mechanisms of compartmentalized expression of Mrg class G-protein-coupled sensory receptors. J Neurosci. 2008;28:125-32 pubmed publisher..Our study suggests a new line of evidence that specification of sensory subtypes is established progressively during perinatal and postnatal development. ..