Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2015

Open Access 01-12-2015 | Research

EVI1 promotes tumor growth via transcriptional repression of MS4A3

Authors: Gerwin Heller, Anna Rommer, Katarina Steinleitner, Julia Etzler, Hubert Hackl, Petra Heffeter, Erwin Tomasich, Martin Filipits, Birgit Steinmetz, Thais Topakian, Simone Klingenbrunner, Barbara Ziegler, Andreas Spittler, Sabine Zöchbauer-Müller, Walter Berger, Rotraud Wieser

Published in: Journal of Hematology & Oncology | Issue 1/2015

Login to get access

Abstract

Background

The transcription factor Ecotropic Virus Integration site 1 (EVI1) regulates cellular proliferation, differentiation, and apoptosis, and its overexpression contributes to an aggressive course of disease in myeloid leukemias and other malignancies. Notwithstanding, knowledge about the target genes mediating its biological and pathological functions remains limited. We therefore aimed to identify and characterize novel EVI1 target genes in human myeloid cells.

Methods

U937T_EVI1, a human myeloid cell line expressing EVI1 in a tetracycline regulable manner, was subjected to gene expression profiling. qRT-PCR was used to confirm the regulation of membrane-spanning-4-domains subfamily-A member-3 (MS4A3) by EVI1. Reporter constructs containing various parts of the MS4A3 upstream region were employed in luciferase assays, and binding of EVI1 to the MS4A3 promoter was investigated by chromatin immunoprecipitation. U937 derivative cell lines experimentally expressing EVI1 and/or MS4A3 were generated by retroviral transduction, and tested for their tumorigenicity by subcutaneous injection into severe combined immunodeficient mice.

Results

Gene expression microarray analysis identified 27 unique genes that were up-regulated, and 29 unique genes that were down-regulated, in response to EVI1 induction in the human myeloid cell line U937T. The most strongly repressed gene was MS4A3, and its down-regulation by EVI1 was confirmed by qRT-PCR in additional, independent experimental model systems. MS4A3 mRNA levels were also negatively correlated with those of EVI1 in several published AML data sets. Reporter gene assays and chromatin immunoprecipitation showed that EVI1 regulated MS4A3 via direct binding to a promoter proximal region. Experimental re-expression of MS4A3 in an EVI1 overexpressing cell line counteracted the tumor promoting effect of EVI1 in a murine xenograft model by increasing the rate of apoptosis.

Conclusions

Our data reveal MS4A3 as a novel direct target of EVI1 in human myeloid cells, and show that its repression plays a role in EVI1 mediated tumor aggressiveness.
Appendix
Available only for authorised users
Literature
1.
Haas K, Kundi M, Sperr W, Esterbauer H, Ludwig W, Ratei R, et al. Expression and prognostic significance of different mRNA 5′-end variants of the oncogene EVI1 in 266 patients with de novo AML: EVI1 and MDS1/EVI1 overexpression both predict short remission duration. Genes Chromosomes Cancer. 2008;47(4):288–98.CrossRefPubMed
2.
Lugthart S, van Drunen E, van Norden Y, van Hoven A, Erpelinck C, Valk P, et al. High EVI1 levels predict adverse outcome in acute myeloid leukemia: prevalence of EVI1 overexpression and chromosome 3q26 abnormalities underestimated. Blood. 2008;111(8):4329–37.CrossRefPubMed
3.
Groschel S, Lugthart S, Schlenk R, Valk P, Eiwen K, Goudswaard C, et al. High EVI1 expression predicts outcome in younger adult patients with acute myeloid leukemia and is associated with distinct cytogenetic abnormalities. J Clin Oncol. 2010;28(12):2101–7.CrossRefPubMed
4.
Vazquez I, Maicas M, Cervera J, Agirre X, Marin-Bejar O, Marcotegui N, et al. Down-regulation of EVI1 is associated with epigenetic alterations and good prognosis in patients with acute myeloid leukemia. Haematologica. 2011;96(10):1448–56.CrossRefPubMedCentralPubMed
5.
Russell M, List A, Greenberg P, Woodward S, Glinsmann B, Parganas E, et al. Expression of EVI1 in myelodysplastic syndromes and other hematologic malignancies without 3q26 translocations. Blood. 1994;84(4):1243–8.PubMed
6.
Dreyfus F, Bouscary D, Melle J, Ribrag V, Guesnu M, Varet B. Expression of the Evi-1 gene in myelodysplastic syndromes. Leukemia. 1995;9(1):203–5.PubMed
7.
Thol F, Yun H, Sonntag A, Damm F, Weissinger E, Krauter J, et al. Prognostic significance of combined MN1, ERG, BAALC, and EVI1 (MEBE) expression in patients with myelodysplastic syndromes. Ann Hematol. 2012;91(8):1221–33.CrossRefPubMed
8.
Ogawa S, Kurokawa M, Tanaka T, Tanaka K, Hangaishi A, Mitani K, et al. Increased Evi-1 expression is frequently observed in blastic crisis of chronic myelocytic leukemia. Leukemia. 1996;10(5):788–94.PubMed
9.
Daghistani M, Marin D, Khorashad J, Wang L, May P, Paliompeis C, et al. EVI-1 oncogene expression predicts survival in chronic-phase CML patients resistant to imatinib treated with second-generation tyrosine kinase inhibitors. Blood. 2010;116(26):6014–7.CrossRefPubMed
10.
Paquette R, Nicoll J, Chalukya M, Elashoff D, Shah N, Sawyers C, et al. Frequent EVI1 translocations in myeloid blast crisis CML that evolves through tyrosine kinase inhibitors. Cancer Genet. 2011;204(7):392–7.CrossRefPubMed
11.
Nanjundan M, Nakayama Y, Cheng K, Lahad J, Liu J, Lu K, et al. Amplification of MDS1/EVI1 and EVI1, located in the 3q26.2 amplicon, is associated with favorable patient prognosis in ovarian cancer. Cancer Res. 2007;67(7):3074–84.CrossRefPubMed
12.
Patel J, Appaiah H, Burnett R, Bhat-Nakshatri P, Wang G, Mehta R, et al. Control of EVI-1 oncogene expression in metastatic breast cancer cells through microRNA miR-22. Oncogene. 2010;30(11):1290–301.CrossRefPubMed
13.
Deng X, Cao Y, Liu Y, Li F, Sambandam K, Rajaraman S, et al. Overexpression of Evi-1 oncoprotein represses TGF-beta signaling in colorectal cancer. Mol Carcinog. 2013;52(4):255–64.CrossRefPubMedCentralPubMed
14.
Tanaka M, Suzuki H, Shibahara J, Kunita A, Isagawa T, Yoshimi A, et al. EVI1 oncogene promotes KRAS pathway through suppression of microRNA-96 in pancreatic carcinogenesis. Oncogene. 2014;33(19):2454–63.CrossRefPubMed
15.
Ho P, Alonzo T, Gerbing R, Pollard J, Hirsch B, Raimondi S, et al. High EVI1 expression is associated with MLL rearrangements and predicts decreased survival in paediatric acute myeloid leukaemia: a report from the children’s oncology group. Br J Haematol. 2013;162(5):670–7.CrossRefPubMedCentralPubMed
16.
Groschel S, Schlenk R, Engelmann J, Rockova V, Teleanu V, Kuhn M, et al. Deregulated expression of EVI1 defines a poor prognostic subset of MLL-rearranged acute myeloid leukemias: a study of the German-Austrian Acute Myeloid Leukemia Study Group and the Dutch-Belgian-Swiss HOVON/SAKK Cooperative Group. J Clin Oncol. 2013;31(1):95–103.CrossRefPubMed
17.
18.
Jin G, Yamazaki Y, Takuwa M, Takahara T, Kaneko K, Kuwata T, et al. Trib1 and Evi1 cooperate with Hoxa and Meis1 in myeloid leukemogenesis. Blood. 2007;109(9):3998–4005.CrossRefPubMed
19.
Watanabe-Okochi N, Kitaura J, Ono R, Harada H, Harada Y, Komeno Y, et al. AML1 mutations induced MDS and MDS/AML in a mouse BMT model. Blood. 2008;111(8):4297–308.CrossRefPubMed
20.
Rommer A, Steinmetz B, Herbst F, Hackl H, Heffeter P, Heilos D, et al. EVI1 inhibits apoptosis induced by antileukemic drugs via upregulation of CDKN1A/p21/WAF in human myeloid cells. PLoS One. 2013;8(2):e56308.CrossRefPubMedCentralPubMed
21.
Sitailo S, Sood R, Barton K, Nucifora C. Forced expression of the leukemia-associated gene EVI1 in ES cells: a model for myeloid leukemia with 3q26 rearrangements. Leukemia. 1999;13(11):1639–45.CrossRefPubMed
22.
Kurokawa M, Mitani K, Yamagata T, Takahashi T, Izutsu K, Ogawa S, et al. The evi-1 oncoprotein inhibits c-Jun N-terminal kinase and prevents stress-induced cell death. EMBO J. 2000;19(12):2958–68.CrossRefPubMedCentralPubMed
23.
Kilbey A, Alzuherri H, McColl J, Cales C, Frampton J, Bartholomew C. The Evi1 proto-oncoprotein blocks endomitosis in megakaryocytes by inhibiting sustained cyclin-dependent kinase 2 catalytic activity. Br J Haematol. 2005;130(6):902–11.CrossRefPubMed
24.
Yuasa H, Oike Y, Iwama A, Nishikata I, Sugiyama D, Perkins A, et al. Oncogenic transcription factor Evi1 regulates hematopoietic stem cell proliferation through GATA-2 expression. EMBO J. 2005;24(11):1976–87.CrossRefPubMedCentralPubMed
25.
Liu Y, Chen L, Ko T, Fields A, Thompson E. Evi1 is a survival factor which conveys resistance to both TGFbeta- and taxol-mediated cell death via PI3K/AKT. Oncogene. 2006;25(25):3565–75.CrossRefPubMed
26.
Laricchia-Robbio L, Nucifora G. Significant increase of self-renewal in hematopoietic cells after forced expression of EVI1. Blood Cells Mol Dis. 2008;40(2):141–7.CrossRefPubMedCentralPubMed
27.
Yamakawa N, Kaneda K, Saito Y, Ichihara E, Morishita K. The increased expression of integrin alpha6 (ITGA6) enhances drug resistance in EVI1(high) leukemia. PLoS One. 2012;7(1):e30706.CrossRefPubMedCentralPubMed
28.
Konantz M, Andre M, Ebinger M, Grauer M, Wang H, Grzywna S, et al. EVI-1 modulates leukemogenic potential and apoptosis sensitivity in human acute lymphoblastic leukemia. Leukemia. 2013;27(1):56–65.CrossRefPubMed
29.
Kustikova O, Schwarzer A, Stahlhut M, Brugman M, Neumann T, Yang M, et al. Activation of Evi1 inhibits cell cycle progression and differentiation of hematopoietic progenitor cells. Leukemia. 2013;27(5):1127–38.CrossRefPubMed
30.
Morishita K, Parganas E, Matsugi T, Ihle J. Expression of the Evi-1 zinc finger gene in 32Dc13 myeloid cells blocks granulocytic differentiation in response to granulocyte colony-stimulating factor. Mol Cell Biol. 1992;12(1):183–9.PubMedCentralPubMed
31.
Kreider B, Orkin S, Ihle J. Loss of erythropoietin responsiveness in erythroid progenitors due to expression of the Evi-1 myeloid-transforming gene. Proc Natl Acad Sci U S A. 1993;90(14):6454–8.CrossRefPubMedCentralPubMed
32.
Kazama H, Kodera T, Shimizu S, Mizoguchi H, Morishita K. Ecotropic viral integration site-1 is activated during, and is sufficient for, neuroectodermal P19 cell differentiation. Cell Growth Differ. 1999;10(8):565–73.PubMed
33.
Shimizu S, Nagasawa T, Katoh O, Komatsu N, Yokota J, Morishita K. EVI1 Is Expressed in Megakaryocyte Cell Lineage and Enforced Expression of EVI1 in UT-7/GM Cells Induces Megakaryocyte Differentiation. Biochem Biophys Res Commun. 2002;292(3):609–16.CrossRefPubMed
34.
Konrad T, Karger A, Hackl H, Schwarzinger I, Herbacek I, Wieser R. Inducible expression of EVI1 in human myeloid cells causes phenotypes consistent with its role in myelodysplastic syndromes. J Leukoc Biol. 2009;86:813–22.CrossRefPubMedCentralPubMed
35.
Karakaya K, Herbst F, Ball C, Glimm H, Kramer A, Loffler H. Overexpression of EVI1 interferes with cytokinesis and leads to accumulation of cells with supernumerary centrosomes in G0/1 phase. Cell Cycle. 2012;11(18):3492–503.CrossRefPubMedCentralPubMed
36.
Steinleitner K, Rampetsreiter P, Koffel R, Ramanathan G, Mannhalter C, Strobl H, et al. EVI1 and MDS1/EVI1 Expression During Primary Human Hematopoietic Progenitor Cell Differentiation into Various Myeloid Lineages. Anticancer Res. 2012;32(11):4883–9.PubMedCentralPubMed
37.
Nayak K, Kuila N, Das Mohapatra A, Panda A, Chakraborty S. EVI1 targets DeltaNp63 and upregulates the cyclin dependent kinase inhibitor p21 independent of p53 to delay cell cycle progression and cell proliferation in colon cancer cells. Int J Biochem Cell Biol. 2013;45(8):1568–76.CrossRefPubMed
38.
Bard-Chapeau E, Jeyakani J, Kok C, Muller J, Chua B, Gunaratne J, et al. Ecotopic viral integration site 1 (EVI1) regulates multiple cellular processes important for cancer and is a synergistic partner for FOS protein in invasive tumors. Proc Natl Acad Sci U S A. 2012;109(6):2168–73.CrossRefPubMedCentralPubMed
39.
Glass C, Wuertzer C, Cui X, Bi Y, Davuluri R, Xiao Y, et al. Global Identification of EVI1 Target Genes in Acute Myeloid Leukemia. PLoS One. 2013;8(6):e67134.CrossRefPubMedCentralPubMed
40.
Shimabe M, Goyama S, Watanabe-Okochi N, Yoshimi A, Ichikawa M, Imai Y, et al. Pbx1 is a downstream target of Evi-1 in hematopoietic stem/progenitors and leukemic cells. Oncogene. 2009;28(49):4364–74.CrossRefPubMed
41.
Yoshimi A, Goyama S, Watanabe-Okochi N, Yoshiki Y, Nannya Y, Nitta E, et al. Evi1 represses PTEN expression and activates PI3K/AKT/mTOR via interactions with polycomb proteins. Blood. 2011;117(13):3617–28.CrossRefPubMed
42.
Saito Y, Kaneda K, Suekane A, Ichihara E, Nakahata S, Yamakawa N, et al. Maintenance of the hematopoietic stem cell pool in bone marrow niches by EVI1-regulated GPR56. Leukemia. 2013;27(8):1637–49.CrossRefPubMed
43.
Gomez-Benito M, Conchillo A, Garcia M, Vazquez I, Maicas M, Vicente C, et al. EVI1 controls proliferation in acute myeloid leukaemia through modulation of miR-1-2. Br J Cancer. 2010;103(8):1292–6.CrossRefPubMedCentralPubMed
44.
Senyuk V, Zhang Y, Liu Y, Ming M, Premanand K, Zhou L, et al. Critical role of miR-9 in myelopoiesis and EVI1-induced leukemogenesis. Proc Natl Acad Sci U S A. 2013;110(14):5594–9.CrossRefPubMedCentralPubMed
45.
Dickstein J, Senyuk V, Premanand K, Laricchia-Robbio L, Xu P, Cattaneo F, et al. Methylation and silencing of miRNA-124 by EVI1 and self-renewal exhaustion of hematopoietic stem cells in murine myelodysplastic syndrome. Proc Natl Acad Sci U S A. 2010;107(21):9783–8.CrossRefPubMedCentralPubMed
46.
Senyuk V, Premanand K, Xu P, Qian Z, Nucifora G. The oncoprotein EVI1 and the DNA methyltransferase Dnmt3 co-operate in binding and de novo methylation of target DNA. PLoS One. 2011;6(6):e20793.CrossRefPubMedCentralPubMed
47.
De Weer A, Van der Meulen J, Rondou P, Taghon T, Konrad T, De Preter K, et al. EVI1-mediated down regulation of miR449A is essential for the survival of EVI1 positive leukaemic cells. Br J Haematol. 2011;154(3):337–48.CrossRefPubMed
48.
Kutok J, Yang X, Folkerth R, Imitola J, Raddassi K, Yano Y, et al. The cell cycle associated protein, HTm4, is expressed in differentiating cells of the hematopoietic and central nervous system in mice. J Mol Histol. 2005;36(1–2):77–87.CrossRefPubMed
49.
Kutok J, Yang X, Folkerth R, Adra C. Characterization of the expression of HTm4 (MS4A3), a cell cycle regulator, in human peripheral blood cells and normal and malignant tissues. J Cell Mol Med. 2011;15(1):86–93.CrossRefPubMedCentralPubMed
50.
51.
Chinami M, Yano Y, Yang X, Salahuddin S, Moriyama K, Shiroishi M, et al. Binding of HTm4 to cyclin-dependent kinase (Cdk)-associated phosphatase (KAP). Cdk2.cyclin A complex enhances the phosphatase activity of KAP, dissociates cyclin A, and facilitates KAP dephosphorylation of Cdk2. J Biol Chem. 2005;280(17):17235–42.CrossRefPubMed
52.
Hamaguchi H, Suzukawa K, Nagata K, Yamamoto K, Yagasaki F, Morishita K. Establishment of a novel human myeloid leukemia cell line (HNT-34) with t(3;3)(q21;q26), t(9;22)(q34;q11) and the expression of EVI1 gene, p210 and p190 BCR/ABL chimaeric transcripts from a patient with AML after MDS with 3q21q26 syndrome. Br J Haematol. 1997;98:399–407.CrossRefPubMed
53.
Hackl H, Rommer A, Konrad T, Nassimbeni C, Wieser R. Tetracycline regulator expression alters the transcriptional program of mammalian cells. PLoS One. 2010;5(9):e13013.CrossRefPubMedCentralPubMed
54.
Saito Y, Nakahata S, Yamakawa N, Kaneda K, Ichihara E, Suekane A, et al. CD52 as a molecular target for immunotherapy to treat acute myeloid leukemia with high EVI1 expression. Leukemia. 2011;25(6):921–31.CrossRefPubMed
55.
Steinmetz B, Hackl H, Slabáková E, Schwarzinger I, Smějová M, Spittler A, et al. The oncogene EVI1 enhances transcriptional and biological responses of human myeloid cells to all-trans retinoic acid. Cell Cycle. 2014;13(18):2931–43.CrossRefPubMed
56.
Oval J, Smedsrud M, Taetle R. Expression and regulation of the evi-1 gene in the human factor-dependent leukemia cell line, UCSD/AML1. Leukemia. 1992;6(5):446–51.PubMed
57.
Verhaak R, Wouters B, Erpelinck C, Abbas S, Beverloo H, Lugthart S, et al. Prediction of molecular subtypes in acute myeloid leukemia based on gene expression profiling. Haematologica. 2009;94(1):131–4.CrossRefPubMedCentralPubMed
58.
Radtke I, Mullighan C, Ishii M, Su X, Cheng J, Ma J, et al. Genomic analysis reveals few genetic alterations in pediatric acute myeloid leukemia. Proc Natl Acad Sci U S A. 2009;106(31):12944–9.CrossRefPubMedCentralPubMed
59.
Shiba N, Ichikawa H, Taki T, Park M, Jo A, Mitani S, et al. NUP98-NSD1 gene fusion and its related gene expression signature are strongly associated with a poor prognosis in pediatric acute myeloid leukemia. Genes Chromosomes Cancer. 2013;52(7):683–93.PubMed
60.
Wieser R. The oncogene and developmental regulator EVI1: expression, biochemical properties, and biological functions. Gene. 2007;396(2):346–57.CrossRefPubMed
61.
Perkins A, Fishel R, Jenkins N, Copeland N. Evi-1, a murine zinc finger proto-oncogene, encodes a sequence-specific DNA-binding protein. Mol Cell Biol. 1991;11(5):2665–74.PubMedCentralPubMed
62.
Delwel R, Funabiki T, Kreider B, Morishita K, Ihle J. Four of the seven zinc fingers of the Evi-1 myeloid-transforming gene are required for sequence-specific binding to GA(C/T)AAGA(T/C)AAGATAA. Mol Cell Biol. 1993;13(7):4291–300.PubMedCentralPubMed
63.
Funabiki T, Kreider B, Ihle J. The carboxyl domain of zinc fingers of the Evi-1 myeloid transforming gene binds a consensus sequence of GAAGATGAG. Oncogene. 1994;9(6):1575–81.PubMed
64.
Tanaka T, Nishida J, Mitani K, Ogawa S, Yazaki Y, Hirai H. Evi-1 raises AP-1 activity and stimulates c-fos promoter transactivation with dependence on the second zinc finger domain. J Biol Chem. 1994;269(39):24020–6.PubMed
65.
Morishita K, Suzukawa K, Taki T, Ihle J, Yokota J. EVI-1 zinc finger protein works as a transcriptional activator via binding to a consensus sequence of GACAAGATAAGATAAN(1-28) CTCATCTTC. Oncogene. 1995;10(10):1961–7.PubMed
66.
Perkins A, Kim J. Zinc fingers 1-7 of EVI1 fail to bind to the GATA motif by itself but require the core site GACAAGATA for binding. J Biol Chem. 1996;271(2):1104–10.CrossRefPubMed
67.
Kim J, Hui P, Yue D, Aycock J, Leclerc C, Bjoring A, et al. Identification of candidate target genes for EVI-1, a zinc finger oncoprotein, using a novel selection strategy. Oncogene. 1998;17(12):1527–38.CrossRefPubMed
68.
Gentles A, Plevritis S, Majeti R, Alizadeh A. Association of a leukemic stem cell gene expression signature with clinical outcomes in acute myeloid leukemia. JAMA. 2010;304(24):2706–15.CrossRefPubMedCentralPubMed
69.
Bao F, Polk P, Nordberg M, Veillon D, Sun A, Deininger M, et al. Comparative gene expression analysis of a chronic myelogenous leukemia cell line resistant to cyclophosphamide using oligonucleotide arrays and response to tyrosine kinase inhibitors. Leuk Res. 2007;31(11):1511–20.CrossRefPubMed
70.
Bindels E, Havermans M, Lugthart S, Erpelinck C, Wocjtowicz E, Krivtsov A, et al. EVI1 is critical for the pathogenesis of a subset of MLL-AF9-rearranged AMLs. Blood. 2012;119(24):5838–49.CrossRefPubMedCentralPubMed
71.
Sturn A, Quackenbush J, Trajanoski Z. Genesis: cluster analysis of microarray data. Bioinformatics. 2002;18(1):207–8.CrossRefPubMed
72.
Bauer S, Grossmann S, Vingron M, Robinson P. Ontologizer 2.0–a multifunctional tool for GO term enrichment analysis and data exploration. Bioinformatics. 2008;24(14):1650–1.CrossRefPubMed
73.
Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Statist Soc B. 1995;57(1):289–300.
74.
Bryne J, Valen E, Tang M, Marstrand T, Winther O, da Piedade I, et al. JASPAR, the open access database of transcription factor-binding profiles: new content and tools in the 2008 update. Nucleic Acids Res. 2008;36(Database issue):D102–106.PubMedCentralPubMed
75.
Quandt K, Frech K, Karas H, Wingender E, Werner T. MatInd and MatInspector: new fast and versatile tools for detection of consensus matches in nucleotide sequence data. Nucleic Acids Res. 1995;23(23):4878–84.CrossRefPubMedCentralPubMed
76.
77.
Livak K, Schmittgen T. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25(4):402–8.CrossRefPubMed
78.
Kollmann K, Heller G, Schneckenleithner C, Warsch W, Scheicher R, Ott R, et al. A kinase-independent function of CDK6 links the cell cycle to tumor angiogenesis. Cancer Cell. 2013;24(2):167–81.CrossRefPubMedCentralPubMed
Metadata
Title
EVI1 promotes tumor growth via transcriptional repression of MS4A3
Authors
Gerwin Heller
Anna Rommer
Katarina Steinleitner
Julia Etzler
Hubert Hackl
Petra Heffeter
Erwin Tomasich
Martin Filipits
Birgit Steinmetz
Thais Topakian
Simone Klingenbrunner
Barbara Ziegler
Andreas Spittler
Sabine Zöchbauer-Müller
Walter Berger
Rotraud Wieser
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2015
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-015-0124-6

Other articles of this Issue 1/2015

Journal of Hematology & Oncology 1/2015 Go to the issue

Case report

Comprehensive serial molecular profiling of an “N of 1” exceptional non-responder with metastatic prostate cancer progressing to small cell carcinoma on treatment

Research

Hematology research output from Chinese authors and other countries: a 10-year survey of the literature

Letter to the Editor

Evaluation of hGM-CSF/hTNFα surface-modified prostate cancer therapeutic vaccine in the huPBL-SCID chimeric mouse model

Research

A novel vaccine for mantle cell lymphoma based on targeting cyclin D1 to dendritic cells via CD40

Review

Blinatumomab: a bispecific T cell engager (BiTE) antibody against CD19/CD3 for refractory acute lymphoid leukemia

Rapid Communication

The serum CXCL13 level is associated with the Glasgow Prognostic Score in extranodal NK/T-cell lymphoma patients
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits