CoChat
Sign Up
Cited by 55Myeloproliferative Neoplasms: Diagnosis and TreatmentPlatelet Disorders and TreatmentsHematological disorders and diagnostics

Philadelphia-negative myeloproliferative neoplasms as disorders marked by cytokine modulation

Open access
Cacemiro, Maira da Costa, Cominal, Juçara Gastaldi, Tognon, Raquel, Nunes, Natalia de Souza, Simões, Belinda Pinto, Figueiredo-Pontes, Lorena Lôbo de, Catto, Luiz Fernando Bazzo, Traina, Fabíola +4 more·2018·Hematology, Transfusion and Cell Therapy
DOI 10.1016/j.htct.2017.12.003PMC PMC6001283
Open this paper in CoChat — free account

Abstract

BACKGROUND: Cytokines are key immune mediators in physiological and disease processes, whose increased levels have been associated with the physiopathology of hematopoietic malignancies, such as myeloproliferative neoplasms. METHODS: This study examined the plasma cytokine profiles of patients with essential thrombocythemia, primary myelofibrosis, polycythemia vera and of healthy subjects, and analyzed correlations with JAK2 V617F status and clinical-hematological parameters. RESULTS: The proinflammatory cytokine levels were increased in myeloproliferative neoplasm patients, and the presence of the JAK2 V617F mutation was associated with high IP-10 levels in primary myelofibrosis patients. CONCLUSIONS: Essential thrombocythemia, primary myelofibrosis, and polycythemia vera patients exhibited different patterns of cytokine production, as revealed by cytokine network correlations. Together, these findings suggest that augmented cytokine levels are associated with the physiopathology of myeloproliferative neoplasms.

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 · 10.1016/j.htct.2017.12.003

Cites

1 of 1 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?

  • The mouse experiments recapitulate chronic inflammation through induction of multiple pro-inflammatory cytokines known to be increased in the serum of patients with MPN, including IFNγ.

    “These experiments recapitulate chronic inflammation through induction of multiple pro-inflammatory cytokines34,35 known to be increased in the serum of patients with MPN36, including IFNγ (Fig. 5a and Extended Data Fig. 10a).”

    From Single-cell multi-omics identifies chronic inflammation as a driver of TP53-mutant leukemic evolution (2023) · cites this paper as [36]

    The Results section (page not provided) reports elevated plasma levels of several cytokines in MPN patients compared with controls. It reports higher IFN-γ in PMF patients than in ET patients, but not compared with healthy controls; the Discussion also recounts a study finding lower IFN-γ in PMF patients than in controls. Thus the source supports the broader cytokine claim, but not the unqualified implication that IFN-γ is increased in MPN patients relative to healthy people. The mouse experiments are not the part attributed to this source. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

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: 41

  1. [1]James C. Ugo V. Le Couédic J.P. Staerk J. Delhommeau F. Lacout C. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera Nature 434 7037 2005 1144 1148 15793561
  2. [2]Tefferi A. Myeloproliferative neoplasms: a decade of discoveries and treatment advances Am J Hematol 91 1 2016 50 58 26492355
  3. [3]Levine R.L. Gilliland D.G. Myeloproliferative disorders Blood 112 6 2008 2190 2198 18779404 PMC2962533
  4. [4]Speletas M. Katodritou E. Daiou C. Mandala E. Papadakis E. Kioumi A. Correlations of JAK2-V617F mutation with clinical and laboratory findings in patients with myeloproliferative disorders Leuk Res 31 8 2007 1053 1062 17045648
  5. [5]Vainchenker W. Constantinescu S.N. A unique activating mutation in JAK2 (V617F) is at the origin of polycythemia vera and allows a new classification of myeloproliferative diseases Hematology Am Soc Hematol Educ Program 2005 195 200 16304380
  6. [6]Landskron G. De la Fuente M. Thuwajit P. Thuwajit C. Hermoso M.A. Chronic inflammation and cytokines in the tumor microenvironment J Immunol Res 2014 2014 149185 24901008 PMC4036716
  7. [7]Rachidi S.M. Qin T. Sun S. Zheng W.J. Li Z. Molecular profiling of multiple human cancers defines an inflammatory cancer-associated molecular pattern and uncovers KPNA2 as a uniform poor prognostic cancer marker PLoS ONE 8 3 2013 e57911 23536776 PMC3607594
  8. [8]Barosi G. An immune dysregulation in MPN Curr Hematol Malig Rep 9 4 2014 331 339 25139710
  9. [9]Hasselbalch H.C. Perspectives on chronic inflammation in essential thrombocythemia, polycythemia vera, and myelofibrosis: is chronic inflammation a trigger and driver of clonal evolution and development of accelerated atherosclerosis and second cancer? Blood 119 14 2012 3219 3225 22318201
  10. [10]Mondet J. Hussein K. Mossuz P. Circulating cytokine levels as markers of inflammation in Philadelphia negative myeloproliferative neoplasms: diagnostic and prognostic interest Mediat Inflamm 2015 2015 670580 PMC4617441 26525644
  11. [11]Stasi R. Zinzani L. Galieni P. Lauta V.M. Damasio E. Dispensa E. Clinical implications of cytokine and soluble receptor measurements in patients with newly-diagnosed aggressive non-Hodgkin's lymphoma Eur J Haematol 54 1 1995 9 17 7859883
  12. [12]Niitsu N. Iijima K. Chizuka A. A high serum-soluble interleukin-2 receptor level is associated with a poor outcome of aggressive non-Hodgkin's lymphoma Eur J Haematol 66 1 2001 24 30 11168504
  13. [13]Li Z.C. Sun M.D. Zheng Y.Q. Fu H.J. The low expression of IL-37 involved in multiple myeloma-associated angiogenesis Med Sci Monit 22 2016 4164 4168 27807338 PMC5098934
  14. [14]Tsirakis G. Roussou P. Pappa C.A. Kolovou A. Vasilokonstantaki C. Miminas I. Increased serum levels of MIP-1alpha correlate with bone disease and angiogenic cytokines in patients with multiple myeloma Med Oncol 31 1 2014 778 24277416
  15. [15]Serio B. Risitano A. Giudice V. Montuori N. Selleri C. Immunological derangement in hypocellular myelodysplastic syndromes Transl Med UniSa 8 2014 31 42 24778996 PMC4000461
  16. [16]Shannon P. Markiel A. Ozier O. Baliga N.S. Wang J.T. Ramage D. Cytoscape: a software environment for integrated models of biomolecular interaction networks Genome Res 13 11 2003 2498 2504 14597658 PMC403769
  17. [18]Taylor R. Interpretation of the correlation coefficient: a basic review J Diagn Med Sonogr 1990 35 39
  18. [19]Luiza-Silva M. Campi-Azevedo A.C. Batista M.A. Martins M.A. Avelar R.S. da Silveira Lemos D. Cytokine signatures of innate and adaptive immunity in 17DD yellow fever vaccinated children and its association with the level of neutralizing antibody J Infect Dis 204 6 2011 873 883 21849284
  19. [20]Vitelli-Avelar D.M. Sathler-Avelar R. Teixeira-Carvalho A. Pinto Dias J.C. Gontijo E.D. Faria A.M. Strategy to assess the overall cytokine profile of circulating leukocytes and its association with distinct clinical forms of human Chagas disease Scand J Immunol 68 5 2008 516 525 18803607
  20. [21]Coelho-dos-Reis J.G. Passos L. Duarte M.C. Araújo M.G. Campi-Azevedo A.C. Teixeira-Carvalho A. Immunological profile of HTLV-1-infected patients associated with infectious or autoimmune dermatological disorders PLoS Negl Trop Dis 7 7 2013 e2328 23936564 PMC3723575
  21. [22]Guimarães A.G. da Costa A.G. Martins-Filho O.A. Pimentel J.P. Zauli D.A. Peruhype-Magalhães V. CD11c+CD123Low dendritic cell subset and the triad TNF-α/IL-17A/IFN-γ integrate mucosal and peripheral cellular responses in HIV patients with high-grade anal intraepithelial neoplasia: a systems biology approach J Acquir Immune Defic Syndr 68 2 2015 112 122 25590266
  22. [23]Them N.C. Kralovics R. Genetic basis of MPN: beyond JAK2-V617F Curr Hematol Malig Rep 8 4 2013 299 306 24190690
  23. [24]Hasselbalch H. Idiopathic myelofibrosis: a clinical study of 80 patients Am J Hematol 34 4 1990 291 300 2195869
  24. [25]Pourcelot E. Trocme C. Mondet J. Bailly S. Toussaint B. Mossuz P. Cytokine profiles in polycythemia vera and essential thrombocythemia patients: clinical implications Exp Hematol 42 5 2014 360 368 24463275
  25. [26]Kobayashi M. Fitz L. Ryan M. Hewick R.M. Clark S.C. Chan S. Identification and purification of natural killer cell stimulatory factor (NKSF), a cytokine with multiple biologic effects on human lymphocytes J Exp Med 170 3 1989 827 845 2504877 PMC2189443
  26. [27]Gately M.K. Renzetti L.M. Magram J. Stern A.S. Adorini L. Gubler U. The interleukin-12/interleukin-12-receptor system: role in normal and pathologic immune responses Annu Rev Immunol 16 1998 495 521 9597139
  27. [28]Qian X. Chen H. Wu X. Hu L. Huang Q. Jin Y. Interleukin-17 acts as double-edged sword in anti-tumor immunity and tumorigenesis Cytokine 89 2017 34 44 26883678
  28. [29]Hanahan D. Coussens L.M. Accessories to the crime: functions of cells recruited to the tumor microenvironment Cancer Cell 21 3 2012 309 322 22439926
  29. [30]Kershaw M.H. Westwood J.A. Darcy P.K. Gene-engineered T cells for cancer therapy Nat Rev Cancer 13 8 2013 525 541 23880905
  30. [31]Gotsch F. Romero R. Friel L. Kusanovic J.P. Espinoza J. Erez O. CXCL10/IP-10: a missing link between inflammation and anti-angiogenesis in preeclampsia? J Matern Fetal Neonatal Med 20 11 2007 777 792 17943641 PMC2396489
  31. [32]Antonelli A. Ferrari S.M. Giuggioli D. Ferrannini E. Ferri C. Fallahi P. Chemokine (C-X-C motif) ligand (CXCL)10 in autoimmune diseases Autoimmun Rev 13 3 2014 272 280 24189283
  32. [33]Raza A. Firasat S. Khaliq S. Aziz T. Mubarak M. Naqvi S.A. The association of urinary interferon-gamma inducible protein-10 (IP10/CXCL10) levels with kidney allograft rejection Inflamm Res 66 5 2017 425 432 28246678
  33. [34]Koschmieder S. Mughal T.I. Hasselbalch H.C. Barosi G. Valent P. Kiladjian J.J. Myeloproliferative neoplasms and inflammation: whether to target the malignant clone or the inflammatory process or both Leukemia 30 5 2016 1018 1024 26854026
  34. [35]Vannucchi A.M. Antonioli E. Guglielmelli P. Pardanani A. Tefferi A. Clinical correlates of JAK2 V617F presence or allele burden in myeloproliferative neoplasms: a critical reappraisal Leukemia 22 7 2008 1299 1307 18496562
  35. [36]Vannucchi A.M. Guglielmelli P. JAK2 mutation-related disease and thrombosis Semin Thromb Hemost 39 5 2013 496 506 23633193
  36. [37]Hasselbalch H.C. Bjørn M.E. MPNs as inflammatory diseases: the evidence, consequences, and perspectives Mediators Inflamm 2015 2015 102476 26604428 PMC4641200
  37. [38]Ho C.L. Lasho T.L. Butterfield J.H. Tefferi A. Global cytokine analysis in myeloproliferative disorders Leuk Res 31 10 2007 1389 1392 17328948
  38. [39]Vaidya R. Gangat N. Jimma T. Finke C.M. Lasho T.L. Pardanani A. Plasma cytokines in polycythemia vera: phenotypic correlates, prognostic relevance, and comparison with myelofibrosis Am J Hematol 87 11 2012 1003 1005 22965887
  39. [40]Tefferi A. Vaidya R. Caramazza D. Finke C. Lasho T. Pardanani A. Circulating interleukin (IL)-8, IL-2R, IL-12, and IL-15 levels are independently prognostic in primary myelofibrosis: a comprehensive cytokine profiling study J Clin Oncol 29 10 2011 1356 1363 21300928
  40. [41]Verstovsek S. Mesa R.A. Gotlib J. Levy R.S. Gupta V. DiPersio J.F. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis N Engl J Med 366 9 2012 799 807 22375971 PMC4822164
  41. [42]Harrison C. Kiladjian J.J. Al-Ali H.K. Gisslinger H. Waltzman R. Stalbovskaya V. JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis N Engl J Med 366 9 2012 787 798 22375970

Cited by

Sorted by citations

Authors
Cacemiro, M. D. C., Cominal, J. G., Tognon, R., Nunes, N. D. S., Simões, B. P., Figueiredo-Pontes, L. L. D., Catto, L. F. B., Traina, F., Souto, E. X., Zambuzi, F. A., Frantz, F. G., & Castro, F. A. D.
Affiliations
  • Universidade de São Paulo (BR)
  • Universidade Federal de Juiz de Fora (BR)
  • Dr. Euryclides Hospital de Jesus Zerbini (BR)
Corresponding author
Cacemiro, Maira da Costa
ORCID
Venue
Hematology, Transfusion and Cell Therapy
Publisher
Elsevier BV
Published
2018-04
Volume
40
Issue
2
Pages
120-131
ISSN
2531-1379 (ISSN-L)
DOI
10.1016/j.htct.2017.12.003
PMC
PMC6001283
OpenAlex
W2790202059
Cited by
55
References
1
Citations by year
2026: 5 · 2025: 9 · 2024: 4 · 2023: 6 · 2022: 7 · 2021: 10 · 2020: 8 · 2019: 5 · 2018: 1
FWCI
3.40
Type
journal article
Language
en
Update notices
erratum (2021-01-01)
Open access
Licence
Locations
  • Hematology Transfusion and Cell Therapy (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (publishedVersion, other-oa)
  • Americanae (AECID Library) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Fundação de Amparo à Pesquisa do Estado de São Paulo (2014/, 2016/03265-3, 2015/, 2014/04234-9, 2015/21237‐4)
  • Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico
Topics
  • Health Sciences › Medicine › Genetics › Myeloproliferative Neoplasms: Diagnosis and Treatment
  • Health Sciences › Medicine › Hematology › Platelet Disorders and Treatments
  • Health Sciences › Medicine › Emergency Medicine › Hematological disorders and diagnostics
Keywords
Philadelphia-negative myeloproliferative neoplasms, cytokines, essential thrombocythemia, primary myelofibrosis, polycythemia vera, JAK2 V617F mutation, CXCL10, inflammatory cytokines, hematological parameters

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