CoChat
Sign Up
Cited by 42Multiple Myeloma Research and TreatmentsNF-κB Signaling PathwaysChronic Lymphocytic Leukemia Research

Targeting NF-κB Signaling for Multiple Myeloma

Open access
Wong, Ada Hang-Heng, Shin, Eun Myoung, Tergaonkar, Vinay, Chng, Wee-Joo·2020·Cancers
DOI 10.3390/cancers12082203PMC PMC7463546
Open this paper in CoChat — free accountOpen PDF

Abstract

Multiple myeloma (MM) is the second most common hematologic malignancy in the world. Even though survival rates have significantly risen over the past years, MM remains incurable, and is also far from reaching the point of being managed as a chronic disease. This paper reviews the evolution of MM therapies, focusing on anti-MM drugs that target the molecular mechanisms of nuclear factor kappa B (NF-κB) signaling. We also provide our perspectives on contemporary research findings and insights for future drug development.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.3390/cancers12082203

Cites

3 of 3 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Approximately 80% of MM patients exhibit elevated levels of NF-κB p65 subunits in bone marrow samples.

    “Approximately 80% of MM patients exhibit elevated levels of NF-κB p65 subunits in bone marrow samples [60, 61, 138, 139].”

    From Multiple myeloma: signaling pathways and targeted therapy (2024) · cites this paper as [138]

    Section 2, “Multiple Myeloma and NF-κB Signaling” (page unavailable), describes intracellular NF-κB hyperactivation in MM cells and identifies RelA as part of the canonical NF-κB complex. It does not report elevated p65 levels in bone marrow samples or establish that approximately 80% of patients have them (searched: 80%, p65, RelA, and bone marrow). (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • Aberrant activation of NF-κB signaling is crucial in MM pathogenesis.

    “The aberrant activation of NF-κB signaling is crucial in MM pathogenesis.”

    From Multiple myeloma: signaling pathways and targeted therapy (2024) · cites this paper as [138]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 129

  1. [1]Kazandjian D. Multiple myeloma epidemiology and survival: A unique malignancy Seminars in Oncology WB Saunders Philadelphia, PA, USA 2016 676 681 PMC5283695 28061985
  2. [2]Palumbo A. Bringhen S. Ludwig H. Dimopoulos M.A. Bladé J. Mateos M.V. Rosiñol L. Boccadoro M. Cavo M. Lokhorst H. Personalized therapy in multiple myeloma according to patient age and vulnerability: A report of the European Myeloma Network (EMN) Blood 2011 118 4519 4529 10.1182/blood-2011-06-358812 21841166 · DOI
  3. [3]Palumbo A. Anderson K. Multiple myeloma N. Engl. J. Med. 2011 364 1046 1060 10.1056/NEJMra1011442 21410373 · DOI
  4. [4]Thorsteinsdottir S. Dickman P.W. Landgren O. Blimark C. Hultcrantz M. Turesson I. Björkholm M. Kristinsson S.Y. Dramatically improved survival in multiple myeloma patients in the recent decade: Results from a Swedish population-based study Haematologica 2018 103 e412 e415 10.3324/haematol.2017.183475 29567776 PMC6119139 · DOI
  5. [6]Fonseca R. Abouzaid S. Bonafede M. Cai Q. Parikh K. Cosler L. Richardson P. Trends in overall survival and costs of multiple myeloma, 2000–2014 Leukemia 2017 31 1915 1921 10.1038/leu.2016.380 28008176 PMC5596206 · DOI
  6. [7]Dimopoulos M.A. Jakubowiak A.J. McCarthy P.L. Orlowski R.Z. Attal M. Bladé J. Goldschmidt H. Weisel K.C. Ramasamy K. Zweegman S. Developments in continuous therapy and maintenance treatment approaches for patients with newly diagnosed multiple myeloma Blood Cancer J. 2020 10 17 10.1038/s41408-020-0273-x 32054831 PMC7018731 · DOI
  7. [8]Cildir G. Low K.C. Tergaonkar V. Noncanonical NF-κB Signaling in Health and Disease Trends Mol. Med. 2016 22 414 429 10.1016/j.molmed.2016.03.002 27068135 · DOI
  8. [9]Puar Y.R. Shanmugam M.K. Fan L. Arfuso F. Sethi G. Tergaonkar V. Evidence for the involvement of the master transcription factor NF-κB in cancer initiation and progression Biomedicines 2018 6 82 10.3390/biomedicines6030082 PMC6163404 30060453 · DOI
  9. [10]Chew C.L. Conos S.A. Unal B. Tergaonkar V. Noncoding RNAs: Master Regulators of Inflammatory Signaling Trends Mol. Med. 2018 24 66 84 10.1016/j.molmed.2017.11.003 29246760 · DOI
  10. [11]Chesi M. Bergsagel P.L. Molecular pathogenesis of multiple myeloma: Basic and clinical updates Int. J. Hematol. 2013 97 313 323 10.1007/s12185-013-1291-2 23456262 PMC3962846 · DOI
  11. [12]Bergsagel P.L. Nardini E. Brents L. Chesi M. Kuehl W.M. IgH translocations in multiple myeloma: A nearly universal event that rarely involves c-myc Current Topics in Microbiology and Immunology Springer Berlin/Heidelberg, Germany 1997 283 287 9308253
  12. [13]Fonseca R. Debes-Marun C.S. Picken E.B. Dewald G.W. Bryant S.C. Winkler J.M. Blood E. Oken M. Santana-Dávila R. González-Paz N. The recurrent IgH translocations are highly associated with nonhyperdiploid variant multiple myeloma Blood 2003 102 2562 2567 10.1182/blood-2003-02-0493 12805059 · DOI
  13. [14]Lohr J.G. Stojanov P. Carter S.L. Cruz-Gordillo P. Lawrence M.S. Auclair D. Sougnez C. Knoechel B. Gould J. Saksena G. Widespread genetic heterogeneity in multiple myeloma: Implications for targeted therapy Cancer Cell 2014 25 91 101 10.1016/j.ccr.2013.12.015 24434212 PMC4241387 · DOI · Paper page
  14. [15]Demchenko Y.N. Michael Kuehl W. A critical role for the NFκB pathway in multiple myeloma Oncotarget 2010 1 59 68 10.18632/oncotarget.109 20890394 PMC2947827 · DOI
  15. [16]Flynt E. Bisht K. Sridharan V. Ortiz M. Towfic F. Thakurta A. Prognosis, Biology, and Targeting of TP53 Dysregulation in Multiple Myeloma Cells 2020 9 287 10.3390/cells9020287 PMC7072230 31991614 · DOI
  16. [17]Keats J.J. Fonseca R. Chesi M. Schop R. Baker A. Chng W.-J. Van Wier S. Tiedemann R. Shi C.-X. Sebag M. Promiscuous Mutations Activate the Noncanonical NF-κB Pathway in Multiple Myeloma Cancer Cell 2007 12 131 144 10.1016/j.ccr.2007.07.003 17692805 PMC2083698 · DOI · Paper page
  17. [18]Walker B.A. Wardell C.P. Chiecchio L. Smith E.M. Boyd K. Neri A. Davies F.E. Ross F.M. Morgan G.J. Aberrant global methylation patterns affect the molecular pathogenesis and prognosis of multiple myeloma Blood 2011 117 553 562 10.1182/blood-2010-04-279539 20944071 · DOI · Paper page
  18. [19]Hodge D.R. Peng B. Cherry J.C. Hurt E.M. Fox S.D. Kelley J.A. Munroe D.J. Farrar W.L. Interleukin 6 supports the maintenance of p53 tumor suppressor gene promoter methylation Cancer Res. 2005 65 4673 4682 10.1158/0008-5472.CAN-04-3589 15930285 · DOI
  19. [20]De Smedt E. Lui H. Maes K. De Veirman K. Menu E. Vanderkerken K. De Bruyne E. The epigenome in multiple myeloma: Impact on tumor cell plasticity and drug response Front. Oncol. 2018 8 566 10.3389/fonc.2018.00566 30619733 PMC6297718 · DOI
  20. [21]Iannetti A. Ledoux A.C. Tudhope S.J. Sellier H. Zhao B. Mowla S. Moore A. Hummerich H. Gewurz B.E. Cockell S.J. Regulation of p53 and Rb Links the Alternative NF-κB Pathway to EZH2 Expression and Cell Senescence PLoS Genet. 2014 10 e1004642 10.1371/journal.pgen.1004642 25255445 PMC4177746 · DOI
  21. [22]Rizq O. Mimura N. Oshima M. Saraya A. Koide S. Kato Y. Aoyama K. Nakajima-Takagi Y. Wang C. Chiba T. Dual Inhibition of EZH2 and EZH1 Sensitizes PRC2-Dependent Tumors to Proteasome Inhibition Clin. Cancer Res. 2017 23 4817 4830 10.1158/1078-0432.CCR-16-2735 28490465 PMC5562278 · DOI · Paper page
  22. [23]Guo M. Price M.J. Patterson D.G. Barwick B.G. Haines R.R. Kania A.K. Bradley J.E. Randall T.D. Boss J.M. Scharer C.D. EZH2 Represses the B Cell Transcriptional Program and Regulates Antibody-Secreting Cell Metabolism and Antibody Production J. Immunol. 2018 200 1039 1052 10.4049/jimmunol.1701470 29288200 PMC5780247 · DOI
  23. [24]Annunziata C.M. Davis R.E. Demchenko Y. Bellamy W. Gabrea A. Zhan F. Lenz G. Hanamura I. Wright G. Xiao W. Frequent Engagement of the Classical and Alternative NF-κB Pathways by Diverse Genetic Abnormalities in Multiple Myeloma Cancer Cell 2007 12 115 130 10.1016/j.ccr.2007.07.004 17692804 PMC2730509 · DOI · Paper page
  24. [25]Demchenko Y.N. Glebov O.K. Zingone A. Keats J.J. Leif Bergsagel P. Michael Kuehl W. Classical and/or alternative NF-κB pathway activation in multiple myeloma Blood 2010 115 3541 3552 10.1182/blood-2009-09-243535 20053756 PMC2867265 · DOI
  25. [26]Pires B.R.B. Silva R.C.M.C. Ferreira G.M. Abdelhay E. NF-kappaB: Two sides of the same coin Genes 2018 9 24 10.3390/genes9010024 29315242 PMC5793177 · DOI
  26. [27]Eluard B. Thieblemont C. Baud V. NF-κB in the New Era of Cancer Therapy Trends Cancer 2020 6 677 687 10.1016/j.trecan.2020.04.003 32409139 · DOI
  27. [28]Dehghanifard A. Kaviani S. Abroun S. Mehdizadeh M. Saiedi S. Maali A. Ghaffari S. Azad M. Various Signaling Pathways in Multiple Myeloma Cells and Effects of Treatment on These Pathways Clin. Lymphoma Myeloma Leuk. 2018 18 311 320 10.1016/j.clml.2018.03.007 29606369 · DOI
  28. [29]Zhang Q. Lenardo M.J. Baltimore D. 30 Years of NF-kB: A Blossoming of Relevance to Human Pathobiology Cell 2017 168 37 57 10.1016/j.cell.2016.12.012 28086098 PMC5268070 · DOI
  29. [30]Shih V.F.S. Tsui R. Caldwell A. Hoffmann A. A single NFκB system for both canonical and non-canonical signaling Cell Res. 2011 21 86 102 10.1038/cr.2010.161 21102550 PMC3193412 · DOI
  30. [31]Xia Y. Shen S. Verma I.M. NF-κB, an active player in human cancers Cancer Immunol. Res. 2014 2 823 830 10.1158/2326-6066.CIR-14-0112 25187272 PMC4155602 · DOI · Paper page
  31. [32]Li Y. Cheng H.S. Chng W.J. Tergaonkar V. Cleaver J.E. Activation of mutant TERT promoter by RAS-ERK signaling is a key step in malignant progression of BRAF-mutant human melanomas Proc. Natl. Acad. Sci. USA 2016 113 14402 14407 10.1073/pnas.1611106113 27911794 PMC5167176 · DOI
  32. [33]Akincilar S.C. Low K.C. Liu C.Y. Yan T.D. Oji A. Ikawa M. Li S. Tergaonkar V. Quantitative assessment of telomerase components in cancer cell lines FEBS Lett. 2015 589 974 984 10.1016/j.febslet.2015.02.035 25749370 · DOI
  33. [34]Khattar E. Maung K.Z.Y. Chew C.L. Ghosh A. Mok M.M.H. Lee P. Zhang J. Chor W.H.J. Cildir G. Wang C.Q. Rap1 regulates hematopoietic stem cell survival and affects oncogenesis and response to chemotherapy Nat. Commun. 2019 10 1 14 10.1038/s41467-019-13082-9 31836706 PMC6911077 · DOI
  34. [35]Ozturk M.B. Li Y. Tergaonkar V. Current insights to regulation and role of telomerase in human diseases Antioxidants 2017 6 17 10.3390/antiox6010017 28264499 PMC5384180 · DOI
  35. [36]Cildir G. Pant H. Lopez A.F. Tergaonkar V. The transcriptional program, functional heterogeneity, and clinical targeting of mast cells J. Exp. Med. 2017 214 2491 2506 10.1084/jem.20170910 28811324 PMC5584128 · DOI
  36. [37]Siveen K.S. Nguyen A.H. Lee J.H. Li F. Singh S.S. Kumar A.P. Low G. Jha S. Tergaonkar V. Ahn K. Negative regulation of signal transducer and activator of transcription-3 signalling cascade by lupeol inhibits growth and induces apoptosis in hepatocellular carcinoma cells Br. J. Cancer 2014 111 1327 1337 10.1038/bjc.2014.422 25101566 PMC4183851 · DOI
  37. [38]Chen D. Frezza M. Schmitt S. Kanwar J. Dou Q.P. Bortezomib as the First Proteasome Inhibitor Anticancer Drug: Current Status and Future Perspectives Curr. Cancer Drug Targets 2011 11 239 253 10.2174/156800911794519752 21247388 PMC3306611 · DOI
  38. [39]Auphan N. DiDonato J.A. Rosette C. Helmberg A. Karin M. Immunosuppression by glucocorticoids: Inhibition of NF-κB activity through induction of IκB synthesis Science 1995 270 286 290 10.1126/science.270.5234.286 7569976 · DOI · Paper page
  39. [40]Oh K.-S. Gottschalk R.A. Lounsbury N.W. Sun J. Dorrington M. Baek S. Sun G. Wang Z. Krauss K.S. Milner J.D. Dual Roles for Ikaros in Regulation of Macrophage Chromatin State and Inflammatory Gene Expression J. Immunol. 2018 201 757 771 10.4049/jimmunol.1800158 29898962 PMC6069956 · DOI
  40. [42]Lu G. Middleton R.E. Sun H. Naniong M. Ott C.J. Mitsiades C.S. Wong K.-K. Bradner J.E. Kaelin W.G. The myeloma drug lenalidomide promotes the cereblon-dependent destruction of ikaros proteins Science 2014 343 305 309 10.1126/science.1244917 24292623 PMC4070318 · DOI · Paper page
  41. [43]Shannon E. Sandoval F. Greig N. Stagg P. Lenalidomide alone or lenalidomide plus dexamethasone significantly inhibit IgG and IgM in vitro⋯A possible explanation for their mechanism of action in treating multiple myeloma Int. Immunopharmacol. 2012 12 441 446 10.1016/j.intimp.2011.12.023 22245427 PMC4978999 · DOI
  42. [44]Moreaux J. Legouffe E. Jourdan E. Quittet P. Rème T. Lugagne C. Moine P. Rossi J.-F. Klein B. Tarte K. BAFF and APRIL protect myeloma cells from apoptosis induced by interleukin 6 deprivation and dexamethasone Blood 2004 103 3148 3157 10.1182/blood-2003-06-1984 15070697 PMC2387243 · DOI · Paper page
  43. [45]Tai Y.T. Li X.F. Breitkreutz I. Song W. Neri P. Catley L. Podar K. Hideshima T. Chauhan D. Raje N. Role of B-cell-activating factor in adhesion and growth of human multiple myeloma cells in the bone marrow microenvironment Cancer Res. 2006 66 6675 6682 10.1158/0008-5472.CAN-06-0190 16818641 · DOI
  44. [46]Mondello P. Cuzzocrea S. Navarra M. Mian M. Bone marrow micro-environment is a crucial player for myelomagenesis and disease progression Oncotarget 2017 8 20394 20409 10.18632/oncotarget.14610 28099912 PMC5386771 · DOI
  45. [47]Pinzone J.J. Hall B.M. Thudi N.K. Vonau M. Qiang Y.-W. Rosol T.J. Shaughnessy J.D. The role of Dickkopf-1 in bone development, homeostasis, and disease Blood 2009 113 517 525 10.1182/blood-2008-03-145169 18687985 PMC2628360 · DOI
  46. [48]Hata H. Bone lesions and macrophage inflammatory protein-1 alpha (MIP-1α) in human multiple myeloma Leuk. Lymphoma 2005 46 967 972 10.1080/10428190500066636 16019547 · DOI
  47. [49]Chng W.J. Glebov O. Bergsagel P.L. Kuehl W.M. Genetic events in the pathogenesis of multiple myeloma Best Pract. Res. Clin. Haematol. 2007 20 571 596 10.1016/j.beha.2007.08.004 18070707 PMC2198931 · DOI
  48. [50]de Weers M. Tai Y.-T. van der Veer M.S. Bakker J.M. Vink T. Jacobs D.C.H. Oomen L.A. Peipp M. Valerius T. Slootstra J.W. Daratumumab, a Novel Therapeutic Human CD38 Monoclonal Antibody, Induces Killing of Multiple Myeloma and Other Hematological Tumors J. Immunol. 2011 186 1840 1848 10.4049/jimmunol.1003032 21187443 · DOI · Paper page
  49. [51]Kaku H. Horikawa K. Obata Y. Kato I. Okamoto H. Sakaguchi N. Gerondakis S. Takatsu K. NF-kB is required for CD38-mediated induction of Cg1 germline transcripts in murine B. lymphocytes Int. Immunol. 2002 14 1055 1064 10.1093/intimm/dxf072 12202402 · DOI
  50. [52]Qian Y. Chen C. Ma L. Wang Z. Wang L.-F. Zuo L. Yang Y. Huang X. Jiang M. Wang X. CD38 Deficiency Promotes Inflammatory Response Through Activating Sirt1/NF-κB-Mediated Inhibition of TLR2 Expression in Macrophages Mediat. Inflamm. 2018 2018 1 13 10.1155/2018/8736949 PMC6011090 29977153 · DOI
  51. [53]Neri P. Kumar S. Fulciniti M.T. Vallet S. Chhetri S. Mukherjee S. Tai Y. Chauhan D. Tassone P. Venuta S. Neutralizing B-cell-activating factor antibody improves survival and inhibits osteoclastogenesis in a severe combined immunodeficient human multiple myeloma model Clin. Cancer Res. 2007 13 5903 5909 10.1158/1078-0432.CCR-07-0753 17908986 · DOI
  52. [54]Blimark C. Holmberg E. Mellqvist U.H. Landgren O. Björkholm M. Hultcrantz M. Kjellander C. Turesson I. Kristinsson S.Y. Multiple myeloma and infections: A population-based study on 9253 multiple myeloma patients Haematologica 2015 100 107 113 10.3324/haematol.2014.107714 25344526 PMC4281323 · DOI
  53. [56]Teh B.W. Harrison S.J. Worth L.J. Thursky K.A. Slavin M.A. Infection risk with immunomodulatory and proteasome inhibitor–based therapies across treatment phases for multiple myeloma: A systematic review and meta-analysis Eur. J. Cancer 2016 67 21 37 10.1016/j.ejca.2016.07.025 27592069 · DOI
  54. [57]Li J. Li Y. Huang B. Zheng D. Chen M. Zhou Z. Drug-Induced Modulation of T Lymphocytes as a Potential Mechanism of Susceptibility to Infections in Patients with Multiple Myeloma During Bortezomib Therapy Cell Biochem. Biophys. 2014 71 457 464 10.1007/s12013-014-0224-x 25343940 PMC4289524 · DOI
  55. [58]Offidani M. Corvatta L. Bringhen S. Gentili S. Gay F. Maracci L. Boccadoro M. Leoni P. Palumbo A. Infection Complications in 476 Patients with Newly Diagnosed Multiple Myeloma Treated with Lenalidomide or Bortezomib Combinations Blood 2015 126 5365 10.1182/blood.V126.23.5365.5365 · DOI
  56. [59]Prescott J. Cook S. Targeting IKKβ in Cancer: Challenges and Opportunities for the Therapeutic Utilisation of IKKβ Inhibitors Cells 2018 7 115 10.3390/cells7090115 PMC6162708 30142927 · DOI
  57. [60]Goldstein D.A. Denosumab for bone lesions in multiple myeloma—What is its value? Haematologica 2018 103 753 754 10.3324/haematol.2017.185264 29712820 PMC5927995 · DOI
  58. [61]Taniguchi K. Karin M. NF-B, inflammation, immunity and cancer: Coming of age Nat. Rev. Immunol. 2018 18 309 324 10.1038/nri.2017.142 29379212 · DOI · Paper page
  59. [62]Ben-Neriah Y. Karin M. Inflammation meets cancer, with NF-κB as the matchmaker Nat. Immunol. 2011 12 715 723 10.1038/ni.2060 21772280 · DOI
  60. [63]Raje N.S. Moreau P. Terpos E. Benboubker L. Grząśko N. Holstein S.A. Oriol A. Huang S.-Y. Beksac M. Kuliczkowski K. Phase 2 study of tabalumab, a human anti-B-cell activating factor antibody, with bortezomib and dexamethasone in patients with previously treated multiple myeloma Br. J. Haematol. 2017 176 783 795 10.1111/bjh.14483 28005265 · DOI
  61. [64]Liu J. Sudom A. Min X. Cao Z. Gao X. Ayres M. Lee F. Cao P. Johnstone S. Plotnikova O. Structure of the nuclear factor κB-inducing kinase (NIK) kinase domain reveals a constitutively active conformation J. Biol. Chem. 2012 287 27326 27334 10.1074/jbc.M112.366658 22718757 PMC3431628 · DOI
  62. [65]Demchenko Y.N. Brents L.A. Li Z. Bergsagel L.P. McGee L.R. Kuehl M.W. Novel inhibitors are cytotoxic for myeloma cells with NFkB inducing kinase-dependent activation of NFkB Oncotarget 2014 5 4554 4566 10.18632/oncotarget.2128 24980832 PMC4147345 · DOI
  63. [66]Rushe M. Silvian L. Bixler S. Chen L.L. Cheung A. Bowes S. Cuervo H. Berkowitz S. Zheng T. Guckian K. Structure of a NEMO/IKK-Associating Domain Reveals Architecture of the Interaction Site Structure 2008 16 798 808 10.1016/j.str.2008.02.012 18462684 · DOI
  64. [67]Habineza Ndikuyeze G. Gaurnier-Hausser A. Patel R. Baldwin A.S. May M.J. Flood P. Krick E. Propert K.J. Mason N.J. A Phase I Clinical Trial of Systemically Delivered NEMO Binding Domain Peptide in Dogs with Spontaneous Activated B-Cell like Diffuse Large B-Cell Lymphoma PLoS ONE 2014 9 e95404 10.1371/journal.pone.0095404 24798348 PMC4010398 · DOI
  65. [68]Xu X. Li Y. Bharath S.R. Ozturk M.B. Bowler M.W. Loo B.Z.L. Tergaonkar V. Song H. Structural basis for reactivating the mutant TERT promoter by cooperative binding of p52 and ETS1 Nat. Commun. 2018 9 3138 10.1038/s41467-018-05644-0 30093619 PMC6085347 · DOI
  66. [69]Greil C. Engelhardt M. Ihorst G. Schoeller K. Bertz H. Marks R. Zeiser R. Duyster J. Einsele H. Finke J. Allogeneic transplantation of multiple myeloma patients may allow long-term survival in carefully selected patients with acceptable toxicity and preserved quality of life Haematologica 2019 104 370 379 10.3324/haematol.2018.200881 30237266 PMC6355495 · DOI
  67. [70]Esma F. Salvini M. Troia R. Boccadoro M. Larocca A. Pautasso C. Melphalan hydrochloride for the treatment of multiple myeloma Expert Opin. Pharmacother. 2017 18 1127 1136 10.1080/14656566.2017.1349102 28658983 · DOI
  68. [71]Kyle R.A. Rajkumar S.V. Multiple myeloma Blood 2008 111 2962 2972 10.1182/blood-2007-10-078022 18332230 PMC2265446 · DOI
  69. [72]Chari A. Vogl D.T. Gavriatopoulou M. Nooka A.K. Yee A.J. Huff C.A. Moreau P. Dingli D. Cole C. Lonial S. Oral Selinexor–Dexamethasone for Triple-Class Refractory Multiple Myeloma N. Engl. J. Med. 2019 381 727 738 10.1056/NEJMoa1903455 31433920 · DOI · Paper page
  70. [73]Bahlis N.J. Sutherland H. White D. Sebag M. Lentzsch S. Kotb R. Venner C.P. Gasparetto C. Del Col A. Neri P. Selinexor plus low-dose bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma Blood 2018 132 2546 2554 10.1182/blood-2018-06-858852 30352784 PMC6302280 · DOI
  71. [74]Van Rhee F. Szmania S.M. Dillon M. Van Abbema A.M. Li X. Stone M.K. Garg T.K. Shi J. Moreno-Bost A.M. Yun R. Combinatorial efficacy of anti-CS1 monoclonal antibody elotuzumab (HuLuc63) and bortezomib against multiple myeloma Mol. Cancer Ther. 2009 8 2616 2624 10.1158/1535-7163.MCT-09-0483 19723891 PMC2748787 · DOI
  72. [75]Cho S.F. Anderson K.C. Tai Y.T. Targeting B cell maturation antigen (BCMA) in multiple myeloma: Potential uses of BCMA-based immunotherapy Front. Immunol. 2018 9 1821 10.3389/fimmu.2018.01821 30147690 PMC6095983 · DOI
  73. [76]Raje N. Berdeja J. Lin Y. Siegel D.S. Jagannath S. Madduri D. Liedtke M. Rosenblatt J. Maus M.V. Turka A. Anti-BCMA CAR T-Cell Therapy bb2121 in Relapsed or Refractory Multiple Myeloma N. Engl. J. Med. 2019 380 1726 1737 10.1056/NEJMoa1817226 31042825 PMC8202968 · DOI · Paper page
  74. [77]Drent E. Themeli M. Poels R. De Jong-Korlaar R. Yuan H. De Bruijn J. Martens A.C. Zweegman S. Van De Donk N.W. Groen R. A Rational Strategy for Reducing On-Target Off-Tumor Effects of CD38-Chimeric Antigen Receptors by Affinity Optimization Mol. Ther. 2017 25 1946 1958 10.1016/j.ymthe.2017.04.024 28506593 PMC5542711 · DOI
  75. [78]Chu J. He S. Deng Y. Zhang J. Peng Y. Hughes T. Yi L. Kwon C.-H. Wang Q.-E. Devine S.M. Genetic modification of T cells redirected toward CS1 enhances eradication of myeloma cells Clin. Cancer Res. 2014 20 3989 4000 10.1158/1078-0432.CCR-13-2510 24677374 PMC4119545 · DOI
  76. [79]D’Agostino M. Raje N. Anti-BCMA CAR T-cell therapy in multiple myeloma: Can we do better? Leukemia 2020 34 21 34 10.1038/s41375-019-0669-4 31780814 · DOI
  77. [80]Jelinek T. Hajek R. PD-1/PD-L1 inhibitors in multiple myeloma: The present and the future Oncoimmunology 2016 5 e1254856 10.1080/2162402X.2016.1254856 28123899 PMC5215080 · DOI
  78. [81]Gowrishankar K. Gunatilake D. Gallagher S.J. Tiffen J. Rizos H. Hersey P. Inducible but Not Constitutive Expression of PD-L1 in Human Melanoma Cells Is Dependent on Activation of NF-κB PLoS ONE 2015 10 e0123410 10.1371/journal.pone.0123410 25844720 PMC4386825 · DOI
  79. [82]Blaquiere N. Castanedo G.M. Burch J.D. Berezhkovskiy L.M. Brightbill H. Brown S. Chan C. Chiang P.C. Crawford J.J. Dong T. Scaffold-Hopping Approach to Discover Potent, Selective, and Efficacious Inhibitors of NF-ÎB Inducing Kinase J. Med. Chem. 2018 61 6801 6813 29940120
  80. [83]Cheng G. Mei X.B. Yan Y. Chen J. Zhang B. Li J. Dong X. Lin N. Zhou Y. Identification of new NIK inhibitors by discriminatory analysis-based molecular docking and biological evaluation Arch. Pharm. (Weinheim) 2019 352 e1800374 10.1002/ardp.201800374 31116887 · DOI
  81. [84]Takakura N. Matsuda M. Khan M. Hiura F. Aoki K. Hirohashi Y. Mori K. Yasuda H. Hirata M. Kitamura C. A novel inhibitor of NF-κB-inducing kinase prevents bone loss by inhibiting osteoclastic bone resorption in ovariectomized mice Bone 2020 135 115316 10.1016/j.bone.2020.115316 32169603 · DOI
  82. [85]Li Z. Li X. Su M.-B. Gao L.-X. Zhou Y.-B. Yuan B. Lyu X. Yan Z. Hu C. Zhang H. Discovery of a Potent and Selective NF-κB-Inducing Kinase (NIK) Inhibitor That Has Anti-inflammatory Effects in Vitro and in Vivo J. Med. Chem. 2020 63 4388 4407 32216342
  83. [86]Fulciniti M. Tassone P. Hideshima T. Vallet S. Nanjappa P. Ettenberg S.A. Shen Z. Patel N. Tai Y. Chauhan D. Anti-DKK1 mAb (BHQ880) as a potential therapeutic agent for multiple myeloma Blood 2009 114 371 379 10.1182/blood-2008-11-191577 19417213 PMC2714212 · DOI
  84. [87]Bianchi G. Oliva L. Cascio P. Pengo N. Fontana F. Cerruti F. Orsi A. Pasqualetto E. Mezghrani A. Calbi V. The proteasome load versus capacity balance determines apoptotic sensitivity of multiple myeloma cells to proteasome inhibition Blood 2009 113 3040 3049 10.1182/blood-2008-08-172734 19164601 · DOI
  85. [88]Scott K. Hayden P.J. Will A. Wheatley K. Coyne I. Bortezomib for the treatment of multiple myeloma Cochrane Database Syst. Rev. 2016 4 CD010816 10.1002/14651858.CD010816.pub2 27096326 PMC10387344 · DOI · Paper page
  86. [89]Chari A. Richardson P.G. Romanus D. Dimopoulos M.A. Sonneveld P. Terpos E. Hajek R. Raju A. Palumbo A. Cain L.E. Real-world outcomes and factors impacting treatment choice in relapsed and/or refractory multiple myeloma (RRMM): A comparison of VRd, KRd, and IRd Expert Rev. Hematol. 2020 13 421 433 10.1080/17474086.2020.1729734 32148109 · DOI
  87. [90]Dimopoulos M. Siegel D. White D.J. Boccia R. Iskander K.S. Yang Z. Kimball A.S. Mezzi K. Ludwig H. Niesvizky R. Carfilzomib vs bortezomib in patients with multiple myeloma and renal failure: A subgroup analysis of ENDEAVOR Blood 2019 133 147 155 10.1182/blood-2018-06-860015 30478094 PMC6346374 · DOI
  88. [91]Dimopoulos M.A. Goldschmidt H. Niesvizky R. Joshua D. Chng W.-J. Oriol A. Orlowski R.Z. Ludwig H. Facon T. Hájek R. Carfilzomib or bortezomib in relapsed or refractory multiple myeloma (ENDEAVOR): An interim overall survival analysis of an open-label, randomised, phase 3 trial Lancet Oncol. 2017 18 1327 1337 10.1016/S1470-2045(17)30578-8 28843768 · DOI
  89. [92]van de Donk N.W. Carfilzomib versus bortezomib: No longer an ENDEAVOR Lancet Oncol. 2017 18 1288 1290 10.1016/S1470-2045(17)30613-7 28843767 · DOI
  90. [93]Siegel D.S. Dimopoulos M.A. Ludwig H. Facon T. Goldschmidt H. Jakubowiak A. San-Miguel J. Obreja M. Blaedel J. Stewart A.K. Improvement in overall survival with carfilzomib, lenalidomide, and dexamethasone in patients with relapsed or refractory multiple myeloma J. Clin. Oncol. 2018 36 728 734 10.1200/JCO.2017.76.5032 29341834 · DOI
  91. [94]Shin E.M. Neja S.A. Fidan K. Chua J.Y.H. Chung T. Bertin N. Tergaonkar V. Chng W. Ooi M.G. Lymphocyte cytosolic protein 1 (LCP1) is a novel TRAF3 dysregulation biomarker with potential prognostic value in multiple myeloma Genome Instab. Dis. 2020 10.1007/s42764-020-00014-x · DOI
  92. [95]Zarnegar B.J. Wang Y. Mahoney D.J. Dempsey P.W. Cheung H.H. He J. Shiba T. Yang X. Yeh W.C. Mak T.W. Noncanonical NF-κB activation requires coordinated assembly of a regulatory complex of the adaptors cIAP1, cIAP2, TRAF2 and TRAF3 and the kinase NIK Nat. Immunol. 2008 9 1371 1378 10.1038/ni.1676 18997794 PMC2676931 · DOI
  93. [96]Vallabhapurapu S. Matsuzawa A. Zhang W.Z. Tseng P.H. Keats J.J. Wang H. Vignali D.A.A. Bergsagel P.L. Karin M. Nonredundant and complementary functions of TRAF2 and TRAF3 in a ubiquitination cascade that activates NIK-dependent alternative NF-κB signaling Nat. Immunol. 2008 9 1364 1370 10.1038/ni.1678 18997792 PMC2671996 · DOI
  94. [98]Mambetsariev N. Lin W.W. Wallis A.M. Stunz L.L. Bishop G.A. TRAF3 deficiency promotes metabolic reprogramming in B cells Sci. Rep. 2016 6 1 9 10.1038/srep35349 27752131 PMC5082756 · DOI
  95. [99]Mambetsarieva N. Lin W.W. Stunza L.L. Hansona B.M. Hildebranda J.M. Bishop G.A. Nuclear TRAF3 is a negative regulator of CREB in B cells Proc. Natl. Acad. Sci. USA 2016 113 1032 1037 10.1073/pnas.1514586113 26755589 PMC4743771 · DOI
  96. [100]Xie P. Stunz L.L. Larison K.D. Yang B. Bishop G.A. Tumor Necrosis Factor Receptor-Associated Factor 3 Is a Critical Regulator of B Cell Homeostasis in Secondary Lymphoid Organs Immunity 2007 27 253 267 10.1016/j.immuni.2007.07.012 17723217 PMC2084086 · DOI
  97. [101]Ma T. Sadashivaiah K. Chellaiah M.A. Regulation of sealing ring formation by L-plastin and cortactin in osteoclasts J. Biol. Chem. 2010 285 29911 29924 10.1074/jbc.M109.099697 20650888 PMC2943304 · DOI
  98. [102]Chellaiah M.A. Majumdar S. Aljohani H. Peptidomimetic inhibitors of L-plastin reduce the resorptive activity of osteoclast but not the bone forming activity of osteoblasts in vitro PLoS ONE 2018 13 e0204209 10.1371/journal.pone.0204209 30248139 PMC6152981 · DOI
  99. [103]Tiedemann K. Sadvakassova G. Mikolajewicz N. Juhas M. Sabirova Z. Tabariès S. Gettemans J. Siegel P.M. Komarova S.V. Exosomal Release of L-Plastin by Breast Cancer Cells Facilitates Metastatic Bone Osteolysis Transl. Oncol. 2019 12 462 474 10.1016/j.tranon.2018.11.014 30583289 PMC6305809 · DOI
  100. [104]Klemke M. Rafael M.T. Wabnitz G.H. Weschenfelder T. Konstandin M.H. Garbi N. Autschbach F. Hartschuh W. Samstag Y. Phosphorylation of ectopically expressed L-plastin enhances invasiveness of human melanoma cells Int. J. Cancer 2007 120 2590 2599 10.1002/ijc.22589 17290393 · DOI
  101. [105]Dun M.D. Chalkley R.J. Faulkner S. Keene S. Avery-Kiejda K.A. Scott R.J. Falkenby L.S. Cairns M.J. Larsen M.R. Bradshaw L.A. Proteotranscriptomic profiling of 231-BR breast cancer cells: Identification of potential biomarkers and therapeutic targets for brain metastasis Mol. Cell. Proteom. 2015 14 2316 2330 10.1074/mcp.M114.046110 26041846 PMC4563718 · DOI
  102. [106]Inaguma S. Riku M. Ito H. Tsunoda T. Ikeda H. Kasai K. GLI1 orchestrates CXCR4/CXCR7 signaling to enhance migration and metastasis of breast cancer cells Oncotarget 2015 6 33648 33657 10.18632/oncotarget.5203 26413813 PMC4741792 · DOI
  103. [107]Otsuka M. Kato M. Yoshikawa T. Chen H. Brown E.J. Masuho Y. Omata M. Seki N. Differential expression of the L-plastin gene in human colorectal cancer progression and metastasis Biochem. Biophys. Res. Commun. 2001 289 876 881 10.1006/bbrc.2001.6047 11735128 · DOI
  104. [108]Foran E. McWilliam P. Kelleher D. Croke D.T. Long A. The leukocyte protein L-plastin induces proliferation, invasion and loss of E-cadherin expression in colon cancer cells Int. J. Cancer 2006 118 2098 2104 10.1002/ijc.21593 16287074 · DOI
  105. [109]Ning Y. Gerger A. Zhang W. Hanna D.L. Yang D. Winder T. Wakatsuki T. Labonte M.J. Stintzing S. Volz N. Plastin polymorphisms predict gender- and stage-specific colon cancer recurrence after adjuvant chemotherapy Mol. Cancer Ther. 2014 13 528 539 10.1158/1535-7163.MCT-13-0646 24170770 PMC3945969 · DOI
  106. [110]Fang Z.-Q. Zang W.-D. Chen R. Ye B. Wang X. Yi S. Chen W. He F. Ye G. Gene expression profile and enrichment pathways in different stages of bladder cancer Genet. Mol. Res. 2013 12 1479 1489 10.4238/2013.May.6.1 23765955 · DOI
  107. [111]Kim D.S. Choi Y.D. Moon M. Kang S. Lim J.B. Kim K.Y. Park K.M. Cho N.H. Composite three-marker assay for early detection of kidney cancer Cancer Epidemiol. Biomark. Prev. 2013 22 390 398 10.1158/1055-9965.EPI-12-1156 23479363 · DOI
  108. [112]Dubovsky J.A. Chappell D.L. Harrington B.K. Agrawal K. Andritsos L.A. Flynn J.M. Jones J.A. Paulaitis M.E. Bolon B. Johnson A.J. Lymphocyte cytosolic protein 1 is a chronic lymphocytic leukemia membrane-associated antigen critical to niche homing Blood 2013 122 3308 3316 10.1182/blood-2013-05-504597 24009233 PMC3953089 · DOI
  109. [113]Freudenmann L.K. Mayer C. Rodemann H.P. Dittmann K. Reduced exosomal L-Plastin is responsible for radiation-induced bystander effect Exp. Cell Res. 2019 383 111498 10.1016/j.yexcr.2019.111498 31302031 · DOI
  110. [114]Bosseler M. Marani V. Broukou A. Lequeux A. Kaoma T. Schlesser V. François J.H. Palissot V. Berchem G.J. Aouali N. Inhibition of HIF1α-dependent upregulation of phospho-L-Plastin resensitizes multiple myeloma cells to frontline therapy Int. J. Mol. Sci. 2018 19 1551 10.3390/ijms19061551 29882856 PMC6032243 · DOI
  111. [115]Majumdar S. Wadajkar A.S. Aljohani H. Reynolds M.A. Kim A.J. Chellaiah M. Engineering of L-Plastin Peptide-Loaded Biodegradable Nanoparticles for Sustained Delivery and Suppression of Osteoclast Function In Vitro Int. J. Cell Biol. 2019 2019 6943986 10.1155/2019/6943986 31191656 PMC6525930 · DOI
  112. [116]Shinohara H. Yasuda T. Aiba Y. Sanjo H. Hamadate M. Watarai H. Sakurai H. Kurosaki T. PKCβ regulates BCR-mediated IKK activation by facilitating the interaction between TAK1 and CARMA1 J. Exp. Med. 2005 202 1423 1431 10.1084/jem.20051591 16301747 PMC2212994 · DOI
  113. [117]Stadanlick J.E. Kaileh M. Karnell F.G. Scholz J.L. Miller J.P. Quinn W.J. Brezski R.J. Treml L.S. Jordan K.A. Monroe J.G. Tonic B cell antigen receptor signals supply an NF-κB substrate for prosurvival BLyS signaling Nat. Immunol. 2008 9 1379 1387 10.1038/ni.1666 18978795 PMC2744141 · DOI
  114. [118]Shinzawa M. Konno H. Qin J. Akiyama N. Miyauchi M. Ohashi H. Miyamoto-Sato H. Yanagawa H. Akiyama T. Inoue J.-i. Catalytic subunits of the phosphatase calcineurin interact with NF-κB-inducing kinase (NIK) and attenuate NIK-dependent gene expression Sci. Rep. 2015 5 10758 10.1038/srep10758 26029823 PMC5377069 · DOI
  115. [119]Wicker L.S. Boltz R.C. Matt V. Nichols E.A. Peterson L.B. Sigal N.H. Suppression of B cell activation by cyclosporin A, FK506 and rapamycin Eur. J. Immunol. 1990 20 2277 2283 10.1002/eji.1830201017 1700753 · DOI
  116. [120]Tan D. Chng W.J. Chou T. Nawarawong W. Hwang S.Y. Chim C.S. Chen W. Durie B.G.M. Lee J.H. Management of multiple myeloma in Asia: Resource-stratified guidelines Lancet Oncol. 2013 14 e571 e581 10.1016/S1470-2045(13)70404-2 24176575 · DOI
  117. [121]Fonseca R. Bergsagel P.L. Drach J. Shaughnessy J. Gutierrez N. Stewart A.K. Morgan G. Van Ness B. Chesi M. Minvielle S. International Myeloma Working Group molecular classification of multiple myeloma: Spotlight review Leukemia 2009 23 2210 2221 10.1038/leu.2009.174 19798094 PMC2964268 · DOI
  118. [122]Varga G. Mikala G. Andrikovics H. Koszarska M. Balassa K. Ádám E. Kozma A. Tordai A. Masszi T. NFKB1 -94ins/delATTG polymorphism is a novel prognostic marker in first line-treated multiple myeloma Br. J. Haematol. 2015 168 679 688 10.1111/bjh.13197 25363231 · DOI
  119. [123]Kumar S. Kaufman J.L. Gasparetto C. Mikhael J. Vig R. Pegouri B. Benboubker R. Facon T. Amiot M. Moreau P. Efficacy of venetoclax as targeted therapy for relapsed/refractory t(11;14) multiple myeloma Blood 2017 130 2401 2409 10.1182/blood-2017-06-788786 29018077 · DOI
  120. [124]Martinez-Garcia E. Popovic R. Min D.J. Sweet S.M.M. Thomas P.M. Zamdborg L. Heffner A. Will C. Lamy L. Staudt L.M. The MMSET histone methyl transferase switches global histone methylation and alters gene expression in t (4;14) multiple myeloma cells Blood 2011 117 211 220 10.1182/blood-2010-07-298349 20974671 PMC3037745 · DOI
  121. [125]Coussens N.P. Kales S.C. Henderson M.J. Lee O.W. Horiuchi K.Y. Wang Y. Chen Q. Kuznetsova E. Wu J. Chakka S. High-throughput screening with nucleosome substrate identifies small-molecule inhibitors of the human histone lysine methyltransferase NSD2 J. Biol. Chem. 2018 293 13750 13765 10.1074/jbc.RA118.004274 29945974 PMC6120216 · DOI
  122. [126]Brighton T.A. Khot A. Harrison S.J. Ghez D. Weiss B.M. Kirsch A. Magen H. Gironella M. Oriol A. Streetly M. Randomized, double-blind, placebo-controlled, multicenter study of siltuximab in high-risk smoldering multiple myeloma Clin. Cancer Res. 2019 25 3772 3775 10.1158/1078-0432.CCR-18-3470 30890552 · DOI
  123. [127]Jonsson B. Nilsson K. Nygren P. Larsson R. SDZ PSC-833—A novel potent in vitro chemosensitizer in multiple myeloma Anticancer Drugs 1992 3 641 646 10.1097/00001813-199212000-00013 1363199 · DOI
  124. [128]Friedenberg W.R. Rue M. Blood E.A. Dalton W.S. Shustik C. Larson R.A. Sonneveld P. Greipp P.R. Phase III study of PSC-833 (valspodar) in combination with vincristine, doxorubicin, and dexamethasone (valspodar/VAD) versus VAD alone in patients with recurring or refractory multiple myeloma (E1A95): A trial of the Eastern Cooperative Oncology Group Cancer 2006 106 830 838 10.1002/cncr.21666 16419071 · DOI
  125. [129]Fassmannová D. Sedlák F. Sedláček J. Špička I. Grantz Šašková K. Nelfinavir Inhibits the TCF11/Nrf1-Mediated Proteasome Recovery Pathway in Multiple Myeloma Cancers 2020 12 1065 10.3390/cancers12051065 PMC7281108 32344880 · DOI
  126. [130]Reddi D.M. Lu C.M. Fedoriw G. Liu Y. Wang F.F. Ely S. Boswell E.L. Louissaint A. Arcasoy M.O. Goodman B.K. Myeloid neoplasms secondary to plasma cell myeloma: An intrinsic predisposition or therapy-related phenomenon? A clinicopathologic study of 41 cases and correlation of cytogenetic features with treatment regimens Am. J. Clin. Pathol. 2012 138 855 866 10.1309/AJCPOP7APGDT9JIU 23161720 · DOI
  127. [131]Klimek V.M. Recent advances in the management of therapy-related myelodysplastic syndromes and acute myeloid leukemia Curr. Opin. Hematol. 2013 20 137 143 10.1097/MOH.0b013e32835d82e6 23343830 · DOI
  128. [132]Pemmaraju N. Shah D. Kantarjian H. Orlowski R.Z. Nogueras González G.M. Baladanayuthapani V. Jain N. Wagner V. Garcia-Manero G. Shah J. Characteristics and outcomes of patients with multiple myeloma who develop therapy-related myelodysplastic syndrome, chronic myelomonocytic leukemia, or acute myeloid leukemia Clin. Lymphoma Myeloma Leuk. 2015 15 110 114 10.1016/j.clml.2014.07.001 25107338 PMC4294996 · DOI
  129. [133]Fernández-Caballero M. Salmerón D. Dolores Chirlaque M. Chen-Liang T.H. Hurtado A.M. García Malo M.D. Ortuño F.J. Roldán V. Vicente V. Jerez A. Increasing therapy-related myeloid neoplasms in multiple myeloma Eur. J. Clin. Investig. 2018 49 e13050 10.1111/eci.13050 30422316 · DOI

Cited by

Sorted by citations

Authors
Wong, A. H.-H., Shin, E. M., Tergaonkar, V., & Chng, W.-J.
Affiliations
  • Agency for Science, Technology and Research (SG)
  • South Australia Pathology (AU)
  • National University of Singapore (SG)
Corresponding author
  • Wong, Ada Hang-Heng
  • Chng, Wee-Joo
ORCID
Venue
Cancers
Publisher
MDPI AG
Published
2020-08-06
Volume
12
Issue
8
Pages
2203
ISSN
2072-6694 (ISSN-L)
DOI
10.3390/cancers12082203
PMC
PMC7463546
OpenAlex
W3047390373
Cited by
42
References
3
Citations by year
2026: 4 · 2025: 5 · 2024: 6 · 2023: 8 · 2022: 6 · 2021: 10 · 2020: 3
FWCI
1.06
Type
journal article
Language
en
Open access
Licence
Locations
  • Cancers (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • National University of Singapore (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
  • Health Sciences › Medicine › Genetics › Chronic Lymphocytic Leukemia Research
Keywords
multiple myeloma, NF-κB signaling, drug development, NF-κB inhibitors, hematologic malignancies, therapeutic target

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review