CoChat
Sign Up
Cited by 39

The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.

BECN1 and BIM interactions with MCL-1 determine fludarabine resistance in leukemic B cells

Sharma, A, Singh, K, Mazumder, S, Hill, B T, Kalaycio, M, Almasan, A·2013·Cell Death & Disease
DOI 10.1038/cddis.2013.155PMC PMC3674362
Open this paper in CoChat — free account

Overview

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 · 10.1038/cddis.2013.155

Cites

5 of 5 references verified0 citation errors · 0 not checkable

Statistics

Figures

Figure 1 Fd induces autophagy and enhances autophagic outflux.(a) Western blot for LC3 I/II expression, with β-actin serving as a loading control, in Nalm-6 and Reh cells treated with Fd for the indicated time. (b) Representative images of LC3 stained cytospins of Nalm-6 cells treated with Fd for 1 h. Nuclei were stained with DAPI. Image quantification of LC3 puncta is shown in (c). (d) Western blot for LC3 I/II, p62/SQSTM1(p62) and β-actin as a loading control in Nalm-6 and Reh cells pretreated with CQ for 1 h followed by 4-h treatment with Fd. (e) Confocal immunostaing for LC3-I/II in Nalm-6 cells pretreated with CQ for 1 h followed by 4-h treatment with Fd. Nuclei were stained with DAPI. Quantification of LC3 puncta staining is shown in (f); *P<0.05, n=3
Figure 1 Fd induces autophagy and enhances autophagic outflux.(a) Western blot for LC3 I/II expression, with β-actin serving as a loading control, in Nalm-6 and Reh cells treated with Fd for the indicated time. (b) Representative images of LC3 stained cytospins of Nalm-6 cells treated with Fd for 1 h. Nuclei were stained with DAPI. Image quantification of LC3 puncta is shown in (c). (d) Western blot for LC3 I/II, p62/SQSTM1(p62) and β-actin as a loading control in Nalm-6 and Reh cells pretreated with CQ for 1 h followed by 4-h treatment with Fd. (e) Confocal immunostaing for LC3-I/II in Nalm-6 cells pretreated with CQ for 1 h followed by 4-h treatment with Fd. Nuclei were stained with DAPI. Quantification of LC3 puncta staining is shown in (f); *P<0.05, n=3CC BY-NC-ND · PubMed Central
Figure 2 Inhibition of autophagy prevents Fd-induced cell death. (a) Cell death analysis in shControl and shLamp2-expressing cells in response to 24-h-Fd treatment as determined by trypan blue staining. (b) Cell death analysis in shControl and shATG7-expressing cells in response to 24-h-Fd treatment as determined by AnnexinV/PI staining. (c) Immunoblotting for levels of LAMP2, p62 and β-actin in Nalm-6 and Reh cells expressing shControl or shLAMP2 lentiviral vectors. (d) Immunoblotting for levels of ATG7, p62 and β-actin in Nalm-6 cells expressing shControl or shATG7. (e) Nalm-6 cells were pretreated with 3-MA for 1 h followed by 24-h-Fd treatment and cell death was determined by AnnexinV/PI staining. All data are expressed as mean±S.D. of percentage of cell death; *P<0.05, **P<0.01, ***P<0.001, n=3
Figure 2 Inhibition of autophagy prevents Fd-induced cell death. (a) Cell death analysis in shControl and shLamp2-expressing cells in response to 24-h-Fd treatment as determined by trypan blue staining. (b) Cell death analysis in shControl and shATG7-expressing cells in response to 24-h-Fd treatment as determined by AnnexinV/PI staining. (c) Immunoblotting for levels of LAMP2, p62 and β-actin in Nalm-6 and Reh cells expressing shControl or shLAMP2 lentiviral vectors. (d) Immunoblotting for levels of ATG7, p62 and β-actin in Nalm-6 cells expressing shControl or shATG7. (e) Nalm-6 cells were pretreated with 3-MA for 1 h followed by 24-h-Fd treatment and cell death was determined by AnnexinV/PI staining. All data are expressed as mean±S.D. of percentage of cell death; *P<0.05, **P<0.01, ***P<0.001, n=3CC BY-NC-ND · PubMed Central
Figure 3 Developing Fd resistance after chronic exposure. (a) Dose reponse for the effect of 24-h-Fd treatment on cell growth in Nalm-6, Nalm-6-FdR, Reh and Reh FdR cells, as determined by the MTS assay. (b) Cell death analysis in the indicated cell lines in response to 24 h Fd treatment as determined by trypan blue staining. (c) Cell death analysis in Nalm-6 and Nalm-6 FdR cells in response to 24 h Fd treatment as determined by AnnexinV/ PI staining. All data are expressed as mean±S.D. of percentage of cell death from three independent experiments. (d) Western blot analysis for the levels of cleaved caspase-3, as well as β-actin as a loading control, in Nalm-6 and Nalm-6-FdR cells treated with the indicated concentrations of bendamustine or Fd for 6 h; **P<0.01, ***P<0.001, ****P<0.0001, n=3
Figure 3 Developing Fd resistance after chronic exposure. (a) Dose reponse for the effect of 24-h-Fd treatment on cell growth in Nalm-6, Nalm-6-FdR, Reh and Reh FdR cells, as determined by the MTS assay. (b) Cell death analysis in the indicated cell lines in response to 24 h Fd treatment as determined by trypan blue staining. (c) Cell death analysis in Nalm-6 and Nalm-6 FdR cells in response to 24 h Fd treatment as determined by AnnexinV/ PI staining. All data are expressed as mean±S.D. of percentage of cell death from three independent experiments. (d) Western blot analysis for the levels of cleaved caspase-3, as well as β-actin as a loading control, in Nalm-6 and Nalm-6-FdR cells treated with the indicated concentrations of bendamustine or Fd for 6 h; **P<0.01, ***P<0.001, ****P<0.0001, n=3CC BY-NC-ND · PubMed Central
Figure 4 FdR cells are addicted to basal autophagy. (a) Western blot analysis for the levels of LC3 I/II and β-actin used as a loading control, in Nalm-6 and their derivative FdR cells in response to fludarabine (Fd)-treatment for the indicated time. (b) Nalm-6 and Nalm-6 FdR cells were pretreated with CQ for 1 h ± Fd (4 h). Cells were then fixed, stained with an antibody against LC3 and LAMP2 along with nuclear staining by DAPI and analyzed by immunofluorescence. (c) Correlation index for LC3 and LAMP2 in the indicated samples. (d) Cell death analysis in ShControl and shLAMP2-expressing Nalm-6 FdR cells in response to 24 h Fd treatment, as determined by trypan blue staining. (e) Western blot analysis for the levels of LAMP2, as well as β-actin in Nalm-6 FdR cells expressing shControl or shLAMP2. (f) Nalm-6 FdR cells were pretreated with CQ for 1 h followed by 24 h Fd treatment and cell death was determined by AnnexinV/PI staining. (g) Dose reponse for the effect of 24 h Fd treatment on cell growth in Mec-2 cells, as determined by the MTS assay. (h) Mec-2 cells were pretreated with CQ for 1 h followed by 24 h Fd treatment and cell death was determined by AnnexinV/PI staining. All data are expressed as mean±S.D. of percentage of cell death from three independent experiments; *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001, n=3
Figure 4 FdR cells are addicted to basal autophagy. (a) Western blot analysis for the levels of LC3 I/II and β-actin used as a loading control, in Nalm-6 and their derivative FdR cells in response to fludarabine (Fd)-treatment for the indicated time. (b) Nalm-6 and Nalm-6 FdR cells were pretreated with CQ for 1 h ± Fd (4 h). Cells were then fixed, stained with an antibody against LC3 and LAMP2 along with nuclear staining by DAPI and analyzed by immunofluorescence. (c) Correlation index for LC3 and LAMP2 in the indicated samples. (d) Cell death analysis in ShControl and shLAMP2-expressing Nalm-6 FdR cells in response to 24 h Fd treatment, as determined by trypan blue staining. (e) Western blot analysis for the levels of LAMP2, as well as β-actin in Nalm-6 FdR cells expressing shControl or shLAMP2. (f) Nalm-6 FdR cells were pretreated with CQ for 1 h followed by 24 h Fd treatment and cell death was determined by AnnexinV/PI staining. (g) Dose reponse for the effect of 24 h Fd treatment on cell growth in Mec-2 cells, as determined by the MTS assay. (h) Mec-2 cells were pretreated with CQ for 1 h followed by 24 h Fd treatment and cell death was determined by AnnexinV/PI staining. All data are expressed as mean±S.D. of percentage of cell death from three independent experiments; *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001, n=3CC BY-NC-ND · PubMed Central
Figure 5 Sustained MCL-1 expression inhibits BECN1-dependent autophagic cell death in FdR cells. (a) Nalm-6 and Nalm-6 FdR, as well as (b) Reh and Reh FdR cells were treated with Fd for the indicated time and 4 h, respectively. Cell lysates were analyzed by western blotting for the indicated proteins. β-actin was used as a loading control. Nalm-6 and Nalm-6 FdR cells were treated with Fd for 24 h, and (c) MCL-1, (d) BCL-2 and (e) BCL-XL immunoprecipitates and whole cell lysates (WCL) were analyzed for the presence of proteins with the corresponding primary antibodies. (f) Cell death analysis in siControl and siBIM-expressing Nalm-6 cells in response to 24 h Fd treatment as determined by trypan blue staining. (g) Immunoblot analysis of BIM and β-actin as a loading control in Nalm-6 cells expressing siControl or siBIM. (h) Nalm-6 and Nalm-6 FdR cells were treated with obatoclax (ob) for 24 h, and MCL-1 immunoprecipitates were analyzed for the presence of the indicated proteins. (i) Nalm-6 and Nalm-6 FdR cells were treated with increasing concentrations of ob for 24 h and the effect on cell viability was assessed by the MTS assay. (j) CLL cells were treated with Fd ± ob (5 μℳ) for 48 h and cell death was determined by AnnexinV/PI staining; **P<0.01, n=6
Figure 5 Sustained MCL-1 expression inhibits BECN1-dependent autophagic cell death in FdR cells. (a) Nalm-6 and Nalm-6 FdR, as well as (b) Reh and Reh FdR cells were treated with Fd for the indicated time and 4 h, respectively. Cell lysates were analyzed by western blotting for the indicated proteins. β-actin was used as a loading control. Nalm-6 and Nalm-6 FdR cells were treated with Fd for 24 h, and (c) MCL-1, (d) BCL-2 and (e) BCL-XL immunoprecipitates and whole cell lysates (WCL) were analyzed for the presence of proteins with the corresponding primary antibodies. (f) Cell death analysis in siControl and siBIM-expressing Nalm-6 cells in response to 24 h Fd treatment as determined by trypan blue staining. (g) Immunoblot analysis of BIM and β-actin as a loading control in Nalm-6 cells expressing siControl or siBIM. (h) Nalm-6 and Nalm-6 FdR cells were treated with obatoclax (ob) for 24 h, and MCL-1 immunoprecipitates were analyzed for the presence of the indicated proteins. (i) Nalm-6 and Nalm-6 FdR cells were treated with increasing concentrations of ob for 24 h and the effect on cell viability was assessed by the MTS assay. (j) CLL cells were treated with Fd ± ob (5 μℳ) for 48 h and cell death was determined by AnnexinV/PI staining; **P<0.01, n=6CC BY-NC-ND · PubMed Central
Figure 6 Basal autophagy in FdR cells is dependent on AMPK but not BECN1. (a) Immunoblot analysis of LC3, BECN1, p62 and β-actin as a loading control in Nalm-6 and Nalm-6 FdR cells expressing siControl or siBECN1 treated with Fd for 4 h. (b) Cell death analysis in siControl and siBECN1-expressing cells in response to 24 h Fd treatment as determined by trypan blue staining *P<0.01, n=3. (c) Immunoblot analysis of p62 and β-actin as a loading control in Nalm-6 FdR cells expressing siControl or siBECN1 treated with obatoclax for 24 h. (d) Cell death analysis in Nalm 6 and FdR Cells in response to serum starvation for the indicated time, as determined by trypan blue staining, ****P<0.0001, n=3. (e) Nalm-6 and Nalm 6 FdR cells were treated with Fd for the indicated time. Cell lysates were analyzed by western blotting for pAMPK-Thr172, AMPK, pULK-1-Ser467 and ULK-1. (f) Nalm-6 and Nalm-6 FdR cells were treated with Comp C ± Fd and Comp C, respectively, for the indicated time and analyzed by western blotting for the levels of pAMPK-Thr172, AMPK, pULK-1-Ser467 and ULK-1
Figure 6 Basal autophagy in FdR cells is dependent on AMPK but not BECN1. (a) Immunoblot analysis of LC3, BECN1, p62 and β-actin as a loading control in Nalm-6 and Nalm-6 FdR cells expressing siControl or siBECN1 treated with Fd for 4 h. (b) Cell death analysis in siControl and siBECN1-expressing cells in response to 24 h Fd treatment as determined by trypan blue staining *P<0.01, n=3. (c) Immunoblot analysis of p62 and β-actin as a loading control in Nalm-6 FdR cells expressing siControl or siBECN1 treated with obatoclax for 24 h. (d) Cell death analysis in Nalm 6 and FdR Cells in response to serum starvation for the indicated time, as determined by trypan blue staining, ****P<0.0001, n=3. (e) Nalm-6 and Nalm 6 FdR cells were treated with Fd for the indicated time. Cell lysates were analyzed by western blotting for pAMPK-Thr172, AMPK, pULK-1-Ser467 and ULK-1. (f) Nalm-6 and Nalm-6 FdR cells were treated with Comp C ± Fd and Comp C, respectively, for the indicated time and analyzed by western blotting for the levels of pAMPK-Thr172, AMPK, pULK-1-Ser467 and ULK-1CC BY-NC-ND · PubMed Central
Figure 7 Model for acquired Fd resistance mechanism. MCL-1 degradation following Fd treatment released BIM and BECN1, leading to apoptosis and cell death-associated autophagy in Fd-sensitive cells. In FdR cells there was low-BIM expression and BECN1 was inhibited by high MCL-1/BECN1 interaction. FdR cells have a higher metabolic demand, which activates AMPK-dependent autophagy and promotes survival in these cells
Figure 7 Model for acquired Fd resistance mechanism. MCL-1 degradation following Fd treatment released BIM and BECN1, leading to apoptosis and cell death-associated autophagy in Fd-sensitive cells. In FdR cells there was low-BIM expression and BECN1 was inhibited by high MCL-1/BECN1 interaction. FdR cells have a higher metabolic demand, which activates AMPK-dependent autophagy and promotes survival in these cellsCC BY-NC-ND · PubMed Central

Verification

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?

Self-check

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

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

Citations

Cites

Show all 5 references

Research works printed but not linked: 37

  1. Van den Neste E, Cardoen S, Offner F, Bontemps F . Old and new insights into the mechanisms of action of two nucleoside analogs active in lymphoid malignancies: fludarabine and cladribine. Int J Oncol 2005; 27: 1113–1124.
  2. Gribben JG, O'Brien S . Update on therapy of chronic lymphocytic leukemia. J Clin Oncol 2011; 29: 544–550. · DOI
  3. Kelly PN, Strasser A . The role of Bcl-2 and its pro-survival relatives in tumourigenesis and cancer therapy. Cell Death Differ 2011; 18: 1414–1424. · DOI
  4. Al-Harbi S, Hill BT, Mazumder S, Singh K, Devecchio J, Choudhary G et al. An antiapoptotic BCL-2 family expression index predicts the response of chronic lymphocytic leukemia to ABT-737. Blood 2011; 118: 3579–3590. · DOI
  5. Mazumder S, Choudhary GS, Al-Harbi S, Almasan A . Mcl-1 Phosphorylation defines ABT-737 resistance that can be overcome by increased NOXA expression in leukemic B cells. Cancer Res 2012; 72: 3069–3079. · DOI
  6. Pepper C, Lin TT, Pratt G, Hewamana S, Brennan P, Hiller L et al. Mcl-1 expression has in vitro and in vivo significance in chronic lymphocytic leukemia and is associated with other poor prognostic markers. Blood 2008; 112: 3807–3817. · DOI
  7. Garcia-Saez AJ . The secrets of the Bcl-2 family. Cell Death Differ 2012; 19: 1733–1740. · DOI
  8. Chen Q, Gong B, Almasan A . Distinct stages of cytochrome c release from mitochondria: evidence for a feedback amplification loop linking caspase activation to mitochondrial dysfunction in genotoxic stress induced apoptosis. Cell Death Differ 2000; 7: 227–233. · DOI
  9. Salvesen GS, Ashkenazi A . Snapshot: caspases. Cell 2011; 147: 476–476 e471. · DOI
  10. Youle RJ, Strasser A . The BCL-2 protein family: opposing activities that mediate cell death. Nat Rev Mol Cell Biol 2008; 9: 47–59. · DOI
  11. Hardwick JM, Chen YB, Jonas EA . Multipolar functions of BCL-2 proteins link energetics to apoptosis. Trends Cell Biol 2012; 22: 318–328. · DOI
  12. Kang R, Zeh HJ, Lotze MT, Tang D . The Beclin 1 network regulates autophagy and apoptosis. Cell Death Differ 2011; 18: 571–580. · DOI · Paper page
  13. Levine B, Sinha S, Kroemer G . Bcl-2 family members: dual regulators of apoptosis and autophagy. Autophagy 2008; 4: 600–606. · DOI
  14. Yorimitsu T, Klionsky DJ . Autophagy: molecular machinery for self-eating. Cell Death Differ 2005; 12 (Suppl 2): 1542–1552. · DOI
  15. Bonapace L, Bornhauser BC, Schmitz M, Cario G, Ziegler U, Niggli FK et al. Induction of autophagy-dependent necroptosis is required for childhood acute lymphoblastic leukemia cells to overcome glucocorticoid resistance. J Clinical Invest 2010; 120: 1310–1323. · DOI
  16. Marquez RT, Xu L . Bcl-2:Beclin 1 complex: multiple, mechanisms regulating autophagy/apoptosis toggle switch. Am J Cancer Res 2012; 2: 214–221.
  17. Chaachouay H, Ohneseit P, Toulany M, Kehlbach R, Multhoff G, Rodemann HP . Autophagy contributes to resistance of tumor cells to ionizing radiation. Radiother Oncol 2011; 99: 287–292. · DOI
  18. Gao W, Shen Z, Shang L, Wang X . Upregulation of human autophagy-initiation kinase ULK1 by tumor suppressor p53 contributes to DNA-damage-induced cell death. Cell Death Differ 2011; 18: 1598–1607. · DOI · Paper page
  19. Laane E, Tamm KP, Buentke E, Ito K, Kharaziha P, Oscarsson J et al. Cell death induced by dexamethasone in lymphoid leukemia is mediated through initiation of autophagy. Cell Death Differ 2009; 16: 1018–1029. · DOI
  20. Kabeya Y, Mizushima N, Uero T, Yamamoto A, Kirisako T, Noda T et al. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J 2000; 19: 5720–5728. · DOI · Paper page
  21. Bjorkoy G, Lamark T, Brech A, Outzen H, Perander M, Overvatn A et al. p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death. J Cell Biol 2005; 171: 603–614. · DOI · Paper page
  22. Gonzalez-Polo RA, Boya P, Pauleau AL, Jalil A, Larochette N, Souquere S et al. The apoptosis/autophagy paradox: autophagic vacuolization before apoptotic death. J Cell Sci 2005; 118: 3091–3102. · DOI
  23. Maiuri MC, Zalckvar E, Kimchi A, Kroemer G . Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nat Rev Mol Cell Biol 2007; 8: 741–752. · DOI
  24. Stacchini A, Aragno M, Vallario A, Alfarano A, Circosta P, Gottardi D et al. MEC1 and MEC2: two new cell lines derived from B-chronic lymphocytic leukaemia in prolymphocytoid transformation. Leuk Res 1999; 23: 127–136. · DOI
  25. Cassano C, Mactier S, Mulligan SP, Belov L, Huang P, Christopherson RI . Cladribine and fludarabine nucleoside change the levels of CD antigens on B-lymphoproliferative disorders. Int J Proteomics 2010; 2010: 964251. · DOI
  26. Egan DF, Shackelford DB, Mihaylova MM, Gelino S, Kohnz RA, Mair W et al. Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy. Science 2011; 331: 456–461. · DOI · Paper page
  27. Levine B, Yuan J . Autophagy in cell death: an innocent convict? J Clin Invest 2005; 115: 2679–2688. · DOI
  28. Denton D, Nicolson S, Kumar S . Cell death by autophagy: facts and apparent artefacts. Cell Death Differ 2012; 19: 87–95. · DOI · Paper page
  29. Mahoney E, Lucas DM, Gupta SV, Wagner AJ, Herman SE, Smith LL et al. ER stress and autophagy: new discoveries in the mechanism of action and drug resistance of the cyclin-dependent kinase inhibitor flavopiridol. Blood 2012; 120: 1262–1273. · DOI
  30. Pattingre S, Tassa A, Qu X, Garuti R, Liang XH, Mizushima N et al. Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell 2005; 122: 927–939. · DOI · Paper page
  31. Maiuri MC, Le Toumelin G, Criollo A, Rain JC, Gautier F, Juin P et al. Functional and physical interaction between Bcl-X(L) and a BH3-like domain in Beclin-1. EMBO J 2007; 26: 2527–2539. · DOI
  32. Bannerji R, Kitada S, Flinn IW, Pearson M, Young D, Reed JC et al. Apoptotic-regulatory and complement-protecting protein expression in chronic lymphocytic leukemia: relationship to in vivo rituximab resistance. J Clin Oncol 2003; 21: 1466–1471. · DOI
  33. Paterson A, Mockridge CI, Adams JE, Krysov S, Potter KN, Duncombe AS et al. Mechanisms and clinical significance of BIM phosphorylation in chronic lymphocytic leukemia. Blood 2012; 119: 1726–1736. · DOI
  34. Zenz T, Krober A, Scherer K, Habe S, Buhler A, Benner A et al. Monoallelic TP53 inactivation is associated with poor prognosis in chronic lymphocytic leukemia: results from a detailed genetic characterization with long-term follow-up. Blood 2008; 112: 3322–3329. · DOI
  35. Chen Q, Chai YC, Mazumder S, Jiang C, Macklis RM, Chisolm GM et al. The late increase in intracellular free radical oxygen species during apoptosis is associated with cytochrome c release, caspase activation, and mitochondrial dysfunction. Cell Death Differ 2003; 10: 323–334. · DOI
  36. Park KJ, Lee SH, Lee CH, Jang JY, Chung J, Kwon MH et al. Upregulation of Beclin-1 expression and phosphorylation of Bcl-2 and p53 are involved in the JNK-mediated autophagic cell death. Biochem Biophys Res Commun 2009; 382: 726–729. · DOI
  37. Bucur O, Stancu AL, Khosravi-Far R, Almasan A . Analysis of apoptosis methods recently used in Cancer Research and Cell Death & Disease publications. Cell Death Dis 2012; 3: e263. · DOI

Cited by

Sorted by citations

Metadata

Authors
Sharma, A., Singh, K., Mazumder, S., Hill, B. T., Kalaycio, M., & Almasan, A.
Venue
Cell Death & Disease
Publisher
Springer Science and Business Media LLC
Published
2013-05-16
Volume
4
Issue
5
Pages
e628-e628
ISSN
2041-4889
DOI
10.1038/cddis.2013.155
PMC
PMC3674362
Cited by
39
References
5
Language
en
Licence
www.springer.com/tdm (unspecified)

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