Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Multiple Myeloma, Gammopathies

The AP-1 transcription factor JunB is essential for multiple myeloma cell proliferation and drug resistance in the bone marrow microenvironment

Leukemia volume 31, pages 1570–1581 (2017)Cite this article

Subjects

Abstract

Despite therapeutic advances, multiple myeloma (MM) remains an incurable disease, predominantly because of the development of drug resistance. The activator protein-1 (AP-1) transcription factor family has been implicated in a multitude of physiologic processes and tumorigenesis; however, its role in MM is largely unknown. Here we demonstrate specific and rapid induction of the AP-1 family member JunB in MM cells when co-cultured with bone marrow stromal cells. Supporting a functional key role of JunB in MM pathogenesis, knockdown of JUNB significantly inhibited in vitro MM cell proliferation and survival. Consistently, induced silencing of JUNB markedly decreased tumor growth in a murine MM model of the microenvironment. Subsequent gene expression profiling revealed a role for genes associated with apoptosis, DNA replication and metabolism in driving the JunB-mediated phenotype in MM cells. Importantly, knockdown of JUNB restored the response to dexamethasone in dexamethasone-resistant MM cells. Moreover, 4-hydroxytamoxifen-induced activation of a JunB-ER fusion protein protected dexamethasone-sensitive MM cells against dexamethasone- and bortezomib-induced cytotoxicity. In summary, our results demonstrate for the first time a specific role for AP-1/JunB in MM cell proliferation, survival and drug resistance, thereby strongly supporting that this transcription factor is a promising new therapeutic target in MM.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6

Similar content being viewed by others

References

  1. Fairfield H, Falank C, Avery L, Reagan MR . Multiple myeloma in the marrow: pathogenesis and treatments. Ann NY Acad Sci 2016; 1364: 32–51.

    Article  CAS  PubMed  Google Scholar 

  2. Podar K, Chauhan D, Anderson KC . Bone marrow microenvironment and the identification of new targets for myeloma therapy. Leukemia 2009; 23: 10–24.

    Article  CAS  PubMed  Google Scholar 

  3. Eychène A, Rocques N, Pouponnot C . A new MAFia in cancer. Nat Rev Cancer 2008; 8: 683–693.

    Article  PubMed  Google Scholar 

  4. Bernstein LR, Colburn NH . AP1/jun function is differentially induced in promotion-sensitive and resistant JB6 cells. Science 1989; 244: 566–569.

    Article  CAS  PubMed  Google Scholar 

  5. Eferl R, Wagner EF . AP-1: a double-edged sword in tumorigenesis. Nat Rev Cancer 2003; 3: 859–868.

    Article  CAS  PubMed  Google Scholar 

  6. Matthews CP, Colburn NH, Young MR . AP-1 a target for cancer prevention. Curr Cancer Drug Targets 2007; 7: 317–324.

    Article  CAS  PubMed  Google Scholar 

  7. Grötsch B, Brachs S, Lang C, Luther J, Derer A, Schlötzer-Schrehardt U et al. The AP-1 transcription factor Fra1 inhibits follicular B cell differentiation into plasma cells. J Exp Med 2014; 211: 2199–2212.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Krum SA, Chang J, Miranda-Carboni G, Wang C-Y . Novel functions for NFκB: inhibition of bone formation. Nat Rev Rheumatol 2010; 6: 607–611.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. De Silva NS, Simonetti G, Heise N, Klein U . The diverse roles of IRF4 in late germinal center B-cell differentiation. Immunol Rev 2012; 247: 73–92.

    Article  PubMed  Google Scholar 

  10. Chesi M, Nardini E, Lim RS, Smith KD, Kuehl WM, Bergsagel PL . The t(4;14) translocation in myeloma dysregulates both FGFR3 and a novel gene, MMSET, resulting in IgH/MMSET hybrid transcripts. Blood 1998; 92: 3025–3034.

    CAS  PubMed  Google Scholar 

  11. Hurt EM, Wiestner A, Rosenwald A, Shaffer AL, Campo E, Grogan T et al. Overexpression of c-maf is a frequent oncogenic event in multiple myeloma that promotes proliferation and pathological interactions with bone marrow stroma. Cancer Cell 2004; 5: 191–199.

    Article  CAS  PubMed  Google Scholar 

  12. Annunziata CM, Hernandez L, Davis RE, Zingone A, Lamy L, Lam LT et al. A mechanistic rationale for MEK inhibitor therapy in myeloma based on blockade of MAF oncogene expression. Blood 2011; 117: 2396–2404.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Podar K, Raab MS, Tonon G, Sattler M, Barilà D, Zhang J et al. Up-regulation of c-Jun inhibits proliferation and induces apoptosis via caspase-triggered c-Abl cleavage in human multiple myeloma. Cancer Res 2007; 67: 1680–1688.

    Article  CAS  PubMed  Google Scholar 

  14. Fan F, Tonon G, Bashari MH, Vallet S, Antonini E, Goldschmidt H et al. Targeting Mcl-1 for multiple myeloma (MM) therapy: Drug-induced generation of Mcl-1 fragment Mcl-1(128-350) triggers MM cell death via c-Jun upregulation. Cancer Lett 2014; 343: 286–294.

    Article  CAS  PubMed  Google Scholar 

  15. Agnelli L, Mosca L, Fabris S, Lionetti M, Andronache A, Kwee I et al. A SNP microarray and FISH-based procedure to detect allelic imbalances in multiple myeloma: an integrated genomics approach reveals a wide gene dosage effect. Genes Chromosomes Cancer 2009; 48: 603–614.

    Article  CAS  PubMed  Google Scholar 

  16. Zhan F, Barlogie B, Arzoumanian V, Huang Y, Williams DR, Hollmig K et al. Gene-expression signature of benign monoclonal gammopathy evident in multiple myeloma is linked to good prognosis. Blood 2007; 109: 1692–1700.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Vasanwala FH, Kusam S, Toney LM, Dent AL . Repression of AP-1 function: a mechanism for the regulation of Blimp-1 expression and B lymphocyte differentiation by the B cell lymphoma-6 protooncogene. J Immunol 2002; 169: 1922–1929.

    Article  CAS  PubMed  Google Scholar 

  18. Bakiri L, Lallemand D, Bossy-Wetzel E, Yaniv M . Cell cycle-dependent variations in c-Jun and JunB phosphorylation: a role in the control of cyclin D1 expression. EMBO J 2000; 19: 2056–2068.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Reich M, Liefeld T, Gould J, Lerner J, Tamayo P, Mesirov JP . GenePattern 2.0. Nat Genet 2006; 38: 500–501.

    Article  CAS  PubMed  Google Scholar 

  20. Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA 2005; 102: 15545–15550.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. McMillin DW, Negri JM, Mitsiades CS . The role of tumour-stromal interactions in modifying drug response: challenges and opportunities. Nat Rev Drug Discov 2013; 12: 217–228.

    Article  CAS  PubMed  Google Scholar 

  22. Kawano M, Hirano T, Matsuda T, Taga T, Horii Y, Iwato K et al. Autocrine generation and requirement of BSF-2/IL-6 for human multiple myelomas. Nature 1988; 332: 83–85.

    Article  CAS  PubMed  Google Scholar 

  23. Klein B, Zhang XG, Lu ZY, Bataille R . Interleukin-6 in human multiple myeloma. Blood 1995; 85: 863–872.

    CAS  PubMed  Google Scholar 

  24. Giuliani N, Rizzoli V, Roodman GD . Multiple myeloma bone disease: pathophysiology of osteoblast inhibition. Blood 2006; 108: 3992–3996.

    Article  CAS  PubMed  Google Scholar 

  25. Greenstein S, Krett NL, Kurosawa Y, Ma C, Chauhan D, Hideshima T et al. Characterization of the MM.1 human multiple myeloma (MM) cell lines: a model system to elucidate the characteristics, behavior, and signaling of steroid-sensitive and -resistant MM cells. Exp Hematol 2003; 31: 271–282.

    Article  CAS  PubMed  Google Scholar 

  26. Brocke-Heidrich K, Kretzschmar AK, Pfeifer G, Henze C, Löffler D, Koczan D et al. Interleukin-6-dependent gene expression profiles in multiple myeloma INA-6 cells reveal a Bcl-2 family-independent survival pathway closely associated with Stat3 activation. Blood 2004; 103: 242–251.

    Article  CAS  PubMed  Google Scholar 

  27. Staber PB, Vesely P, Haq N, Ott RG, Funato K, Bambach I et al. The oncoprotein NPM-ALK of anaplastic large-cell lymphoma induces JUNB transcription via ERK1/2 and JunB translation via mTOR signaling. Blood 2007; 110: 3374–3383.

    Article  CAS  PubMed  Google Scholar 

  28. Mathas S, Hinz M, Anagnostopoulos I, Krappmann D, Lietz A, Jundt F et al. Aberrantly expressed c-Jun and JunB are a hallmark of Hodgkin lymphoma cells, stimulate proliferation and synergize with NF-kappa B. EMBO J 2002; 21: 4104–4113.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Watanabe M, Sasaki M, Itoh K, Higashihara M, Umezawa K, Kadin ME et al. JunB induced by constitutive CD30-extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase signaling activates the CD30 promoter in anaplastic large cell lymphoma and reed-sternberg cells of Hodgkin lymphoma. Cancer Res 2005; 65: 7628–7634.

    Article  CAS  PubMed  Google Scholar 

  30. Watanabe M, Itoh K, Togano T, Kadin ME, Watanabe T, Higashihara M et al. Ets-1 activates overexpression of JunB and CD30 in Hodgkin’s lymphoma and anaplastic large-cell lymphoma. Am J Pathol 2012; 180: 831–838.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Lodé L, Moreau P, Ménard A, Godon C, Touzeau C, Amiot M et al. Lack of BRAF V600E mutation in human myeloma cell lines established from myeloma patients with extramedullary disease. Blood Cancer J 2013; 3: e163.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Bolick SCE, Landowski TH, Boulware D, Oshiro MM, Ohkanda J, Hamilton AD et al. The farnesyl transferase inhibitor, FTI-277, inhibits growth and induces apoptosis in drug-resistant myeloma tumor cells. Leukemia 2003; 17: 451–457.

    Article  CAS  PubMed  Google Scholar 

  33. Suzuki R, Kikuchi S, Harada T, Mimura N, Minami J, Ohguchi H et al. Combination of a Selective HSP90α/β Inhibitor and a RAS-RAF-MEK-ERK Signaling Pathway Inhibitor Triggers Synergistic Cytotoxicity in Multiple Myeloma Cells. PLoS One 2015; 10: e0143847.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Shaulian E, Karin M . AP-1 as a regulator of cell life and death. Nat Cell Biol 2002; 4: E131–E136.

    Article  CAS  PubMed  Google Scholar 

  35. Passegué E, Jochum W, Schorpp-Kistner M, Möhle-Steinlein U, Wagner EF . Chronic myeloid leukemia with increased granulocyte progenitors in mice lacking junB expression in the myeloid lineage. Cell 2001; 104: 21–32.

    Article  PubMed  Google Scholar 

  36. Ott RG, Simma O, Kollmann K, Weisz E, Zebedin EM, Schorpp-Kistner M et al. JunB is a gatekeeper for B-lymphoid leukemia. Oncogene 2007; 26: 4863–4871.

    Article  CAS  PubMed  Google Scholar 

  37. Kanno T, Kamba T, Yamasaki T, Shibasaki N, Saito R, Terada N et al. JunB promotes cell invasion and angiogenesis in VHL-defective renal cell carcinoma. Oncogene 2012; 31: 3098–3110.

    Article  CAS  PubMed  Google Scholar 

  38. Rassidakis GZ, Thomaides A, Atwell C, Ford R, Jones D, Claret F-X et al. JunB expression is a common feature of CD30+ lymphomas and lymphomatoid papulosis. Mod Pathol 2005; 18: 1365–1370.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Mao X, Orchard G, Lillington DM, Russell-Jones R, Young BD, Whittaker SJ . Amplification and overexpression of JUNB is associated with primary cutaneous T-cell lymphomas. Blood 2003; 101: 1513–1519.

    Article  CAS  PubMed  Google Scholar 

  40. Mao X, Orchard G, Lillington DM, Child FJ, Vonderheid EC, Nowell PC et al. BCL2 and JUNB abnormalities in primary cutaneous lymphomas. Br J Dermatol 2004; 151: 546–556.

    Article  CAS  PubMed  Google Scholar 

  41. Choo KB, Huang CJ, Chen CM, Han CP, Au LC . Jun-B oncogene aberrations in cervical cancer cell lines. Cancer Lett 1995; 93: 249–253.

    Article  CAS  PubMed  Google Scholar 

  42. Bamberger AM, Milde-Langosch K, Rössing E, Goemann C, Löning T . Expression pattern of the AP-1 family in endometrial cancer: correlations with cell cycle regulators. J Cancer Res Clin Oncol 2001; 127: 545–550.

    Article  CAS  PubMed  Google Scholar 

  43. Wang H, Birkenbach M, Hart J . Expression of Jun family members in human colorectal adenocarcinoma. Carcinogenesis 2000; 21: 1313–1317.

    Article  CAS  PubMed  Google Scholar 

  44. Halazonetis TD, Georgopoulos K, Greenberg ME, Leder P . c-Jun dimerizes with itself and with c-Fos, forming complexes of different DNA binding affinities. Cell 1988; 55: 917–924.

    Article  CAS  PubMed  Google Scholar 

  45. Angel P, Imagawa M, Chiu R, Stein B, Imbra RJ, Rahmsdorf HJ et al. Phorbol ester-inducible genes contain a common cis element recognized by a TPA-modulated trans-acting factor. Cell 1987; 49: 729–739.

    Article  CAS  PubMed  Google Scholar 

  46. Chinenov Y, Kerppola TK . Close encounters of many kinds: Fos-Jun interactions that mediate transcription regulatory specificity. Oncogene 2001; 20: 2438–2452.

    Article  CAS  PubMed  Google Scholar 

  47. Macián F, López-Rodríguez C, Rao A . Partners in transcription: NFAT and AP-1. Oncogene 2001; 20: 2476–2489.

    Article  PubMed  Google Scholar 

  48. van Dam H, Castellazzi M . Distinct roles of Jun: Fos and Jun: ATF dimers in oncogenesis. Oncogene 2001; 20: 2453–2464.

    Article  CAS  PubMed  Google Scholar 

  49. Johannessen CM, Johnson LA, Piccioni F, Townes A, Frederick DT, Donahue MK et al. A melanocyte lineage program confers resistance to MAP kinase pathway inhibition. Nature 2013; 504: 138–142.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Chauhan D, Li G, Hideshima T, Podar K, Mitsiades C, Mitsiades N et al. Hsp27 inhibits release of mitochondrial protein Smac in multiple myeloma cells and confers dexamethasone resistance. Blood 2003; 102: 3379–3386.

    Article  CAS  PubMed  Google Scholar 

  51. Tian Z, D’Arcy P, Wang X, Ray A, Tai Y-T, Hu Y et al. A novel small molecule inhibitor of deubiquitylating enzyme USP14 and UCHL5 induces apoptosis in multiple myeloma and overcomes bortezomib resistance. Blood 2014; 123: 706–716.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Chauhan D, Tian Z, Nicholson B, Kumar KGS, Zhou B, Carrasco R et al. A small molecule inhibitor of ubiquitin-specific protease-7 induces apoptosis in multiple myeloma cells and overcomes bortezomib resistance. Cancer Cell 2012; 22: 345–358.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Bhagwat AS, Vakoc CR . Targeting transcription factors in cancer. Trends Cancer 2015; 1: 53–65.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Chesi M, Bergsagel PL . Advances in the pathogenesis and diagnosis of multiple myeloma. Int J Lab Hematol 2015; 37 (Suppl 1): 108–114.

    Article  PubMed  Google Scholar 

  55. Yeh JE, Toniolo PA, Frank DA . Targeting transcription factors: promising new strategies for cancer therapy. Curr Opin Oncol 2013; 25: 652–658.

    Article  CAS  PubMed  Google Scholar 

  56. Delmore JE, Issa GC, Lemieux ME, Rahl PB, Shi J, Jacobs HM et al. BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell 2011; 146: 904–917.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Ria R, Catacchio I, Berardi S, De Luisi A, Caivano A, Piccoli C et al. HIF-1α of bone marrow endothelial cells implies relapse and drug resistance in patients with multiple myeloma and may act as a therapeutic target. Clin Cancer Res 2014; 20: 847–858.

    Article  CAS  PubMed  Google Scholar 

  58. Borsi E, Terragna C, Brioli A, Tacchetti P, Martello M, Cavo M . Therapeutic targeting of hypoxia and hypoxia-inducible factor 1 alpha in multiple myeloma. Transl Res 2015; 165: 641–650.

    Article  CAS  PubMed  Google Scholar 

  59. Fulciniti M, Amin S, Nanjappa P, Rodig S, Prabhala R, Li C et al. Significant biological role of sp1 transactivation in multiple myeloma. Clin Cancer Res 2011; 17: 6500–6509.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Ye N, Ding Y, Wild C, Shen Q, Zhou J . Small molecule inhibitors targeting activator protein 1 (AP-1). J Med Chem 2014; 57: 6930–6948.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank the microarray unit of the German Cancer Research Center (DKFZ) Genomics and Proteomics Core Facility for providing the Illumina Whole-Genome Expression Beadchips and related services. We thank Dr Peter Angel, Dr Marina Schorpp-Kistner from DKFZ as well as Dr Jochen Hess from University Heidelberg and DKFZ for providing the luminometer; and Haifan Huang, Jian Xu and Yingying Liang from the Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China, for technical help. This work was supported by B Braun Stiftungs-Grant (to KP). MHB is the recipient of the DAAD-Indonesian German Scholarship Programme for doctoral fellowship. GT is supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC; Investigator Grants and Special Program Molecular Clinical Oncology, 5 per mille no. 9965). AS and DH are supported by grants from the Deutsche Forschungsgemeinschaft, SFB/TRR79 (Bonn, Germany), and the EU 7th framework program (OverMyR). CRB and HG are supported by the German Research Council (DFG; KFO 227), the Baden-Württemberg Stiftung and the DFG Collaborative Research Center 873. HG is supported by the Dietmar Hopp Stiftung, the German Ministry of Education and Science and the DFG. EFW is funded by the Banco Bilbao Vizcaya Argentaria (BBVA) Foundation and a European Research Council Advanced Grant (ERC FCK/2008/37). PT is the recipient of the Italian Association for Cancer Research (AIRC) ‘Special Program Molecular Clinical Oncology - 5 per mille’ no. 9980, 2010/15. DJ is supported by the Heidelberg University Association Grant, DKFZ—HIPO H034, Dietmar Hopp Stiftung and the DFG.

Author contributions

FF conceived and designed the experiments, performed experiments, analyzed data and wrote the manuscript. MHB performed experiments and analyzed data. EM performed in vivo experiments. GT participated in data analysis and interpretation. SM, SV and MJ performed experiments. AS, DH, LB, CS and YH contributed essential experimental tools, participated in designing experiments and interpreted data. CRB, HG, MS, HG, EFW, PT and DJ participated in conceiving the study and in the interpretation of data. KP conceived the study, designed experiments, analyzed and interpreted data and wrote the manuscript.

Author information

Author notes

  1. M H Bashari and E Morelli: These authors contributed equally to this work.

Authors and Affiliations

  1. Medical Oncology, National Center for Tumor Diseases (NCT), University of Heidelberg, Heidelberg, Germany

    F Fan, M H Bashari, S Malvestiti, S Vallet, M Jarahian, D Jaeger & K Podar

  2. Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

    F Fan, C Sun & Y Hu

  3. University ‘Magna Græcia’ of Catanzaro, Catanzaro, Italy

    E Morelli & P Tassone

  4. Division of Experimental Oncology, Functional Genomics of Cancer Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy

    G Tonon

  5. Department of Internal Medicine V, Section Multiple Myeloma, National Center for Tumor Diseases (NCT), University of Heidelberg, Heidelberg, Germany

    A Seckinger, D Hose & H Goldschmidt

  6. Genes Development and Disease Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain

    L Bakiri & E F Wagner

  7. Department of Translational Oncology, National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), Heidelberg, Germany,

    C R Ball & H Glimm

  8. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

    M Sattler

  9. Karl Landsteiner University of Health Sciences, University Hospital Krems, Krems an der Donau, Austria,

    K Podar

Authors
  1. F Fan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M H Bashari
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. E Morelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. G Tonon
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S Malvestiti
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. S Vallet
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M Jarahian
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. A Seckinger
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. D Hose
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. L Bakiri
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. C Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Y Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. C R Ball
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. H Glimm
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. M Sattler
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. H Goldschmidt
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. E F Wagner
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. P Tassone
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. D Jaeger
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. K Podar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to K Podar.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies this paper on the Leukemia website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fan, F., Bashari, M., Morelli, E. et al. The AP-1 transcription factor JunB is essential for multiple myeloma cell proliferation and drug resistance in the bone marrow microenvironment. Leukemia 31, 1570–1581 (2017). https://doi.org/10.1038/leu.2016.358

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/leu.2016.358

This article is cited by

Search

Advanced search

Quick links