CoChat
Sign Up
Cited by 170Cardiac Fibrosis and RemodelingMyeloproliferative Neoplasms: Diagnosis and TreatmentAtherosclerosis and Cardiovascular Diseases

JAK2V617F-Mediated Clonal Hematopoiesis Accelerates Pathological Remodeling in Murine Heart Failure

Open access
Sano, Soichi, Wang, Ying, Yura, Yoshimitsu, Sano, Miho, Oshima, Kosei, Yang, Yue, Katanasaka, Yasufumi, Min, Kyung-Duk +4 more·2019·JACC: Basic to Translational Science
DOI 10.1016/j.jacbts.2019.05.013PMC PMC6834960
Open this paper in CoChat — free accountOpen PDF

Abstract

Janus kinase 2 (valine to phenylalanine at residue 617) (JAK2V617F) mutations lead to myeloproliferative neoplasms associated with elevated myeloid, erythroid, and megakaryocytic cells. Alternatively these same mutations can lead to the condition of clonal hematopoiesis with no impact on blood cell counts. Here, a model of myeloid-restricted JAK2V617F expression from lineage-negative bone marrow cells was developed and evaluated. This model displayed greater cardiac inflammation and dysfunction following permanent left anterior descending artery ligation and transverse aortic constriction. These data suggest that JAK2V617Fmutations arising in myeloid progenitor cells may contribute to cardiovascular disease by promoting the proinflammatory properties of circulating myeloid cells.

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.jacbts.2019.05.013

Cites

6 of 6 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?

  • In a Jak2 mutation model of coronary artery ligation and heart failure, recipients of mutant myeloid cells show larger infarct size, increased cardiac hypertrophy, and eventually increased fibrosis.

    “the authors showed in recipients of the mutant myeloid cells that there was larger infarct size, increased cardiac hypertrophy, and eventually increased fibrosis [38].”

    From Clonal hematopoiesis and inflammation – the perpetual cycle (2023) · cites this paper as [38]

    The Results section on experimental MI reports enlarged infarct areas and increased fibrosis after LAD ligation in recipients of myeloid-specific JAK2V617F cells (Figure 3E). It reports increased cardiac hypertrophy in a separate pressure-overload model (Figure 4), not in the LAD-ligation model, so the claim conflates the two experiments. (LLM, conf=0.88)

    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: 64

  1. [1]Fuster J.J. Walsh K. Somatic mutations and clonal hematopoiesis: unexpected potential new drivers of age-related cardiovascular disease Circ Res 122 2018 523 532 29420212 PMC5826570
  2. [2]Sano S. Wang Y. Walsh K. Clonal hematopoiesis and its impact on cardiovascular disease Circ J 83 2018 2 11 30185689 PMC6310086
  3. [3]Jan M. Ebert B.L. Jaiswal S. Clonal hematopoiesis Semin Hematol 54 2017 43 50 28088988 PMC8045769
  4. [5]Busque L. Patel J.P. Figueroa M.E. Recurrent somatic TET2 mutations in normal elderly individuals with clonal hematopoiesis Nat Genet 44 2012 1179 1181 23001125 PMC3483435
  5. [7]Coombs C.C. Zehir A. Devlin S.M. Therapy-related clonal hematopoiesis in patients with non-hematologic cancers is common and associated with adverse clinical outcomes Cell Stem Cell 21 2017 374 382 e4 28803919 PMC5591073
  6. [8]Genovese G. Kahler A.K. Handsaker R.E. Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence N Engl J Med 371 2014 2477 2487 25426838 PMC4290021
  7. [9]Gibson C.J. Lindsley R.C. Tchekmedyian V. Clonal hematopoiesis associated with adverse outcomes after autologous stem-cell transplantation for lymphoma J Clin Oncol 35 2017 1598 1605 28068180 PMC5455707
  8. [11]Loh P.R. Genovese G. Handsaker R.E. Insights into clonal haematopoiesis from 8,342 mosaic chromosomal alterations Nature 559 2018 350 355 29995854 PMC6054542
  9. [12]Zink F. Stacey S.N. Norddahl G.L. Clonal hematopoiesis, with and without candidate driver mutations, is common in the elderly Blood 130 2017 742 752 28483762 PMC5553576
  10. [13]Jaiswal S. Natarajan P. Silver A.J. Clonal hematopoiesis and risk of atherosclerotic cardiovascular disease N Engl J Med 377 2017 111 121 28636844 PMC6717509
  11. [14]Sano S. Oshima K. Wang Y. Tet2-mediated clonal hematopoiesis accelerates heart failure through a mechanism involving the IL-1beta/NLRP3 inflammasome J Am Coll Cardiol 71 2018 875 886 29471939 PMC5828038
  12. [15]Fuster J.J. MacLauchlan S. Zuriaga M.A. Clonal hematopoiesis associated with TET2 deficiency accelerates atherosclerosis development in mice Science 355 2017 842 847 28104796 PMC5542057
  13. [16]Sano S. Oshima K. Wang Y. CRISPR-mediated gene editing to assess the roles of Tet2 and Dnmt3a in clonal hematopoiesis and cardiovascular disease Circ Res 123 2018 335 341 29728415 PMC6054544
  14. [17]Dorsheimer L. Assmus B. Rasper T Association of mutations contributing to clonal hematopoiesis with prognosis in chronic ischemic heart failure JAMA Cardiol 4 2019 25 33 30566180 PMC6439691
  15. [18]Spivak J.L. Myeloproliferative Neoplasms N Engl J Med 376 2017 2168 2181 28564565
  16. [19]Tefferi A. Pardanani A. Myeloproliferative neoplasms: a contemporary review JAMA Oncol 1 2015 97 105 26182311
  17. [20]Nielsen C. Birgens H.S. Nordestgaard B.G. Bojesen S.E. Diagnostic value of JAK2 V617F somatic mutation for myeloproliferative cancer in 49 488 individuals from the general population Br J Haematol 160 2013 70 79 23116358
  18. [21]Nielsen C. Birgens H.S. Nordestgaard B.G. Kjaer L. Bojesen S.E. The JAK2 V617F somatic mutation, mortality and cancer risk in the general population Haematologica 96 2011 450 453 21160067 PMC3046277
  19. [22]Sidon P. El Housni H. Dessars B. Heimann P. The JAK2V617F mutation is detectable at very low level in peripheral blood of healthy donors Leukemia 20 2006 1622 16775613
  20. [23]Xu X. Zhang Q. Luo J. JAK2(V617F): Prevalence in a large Chinese hospital population Blood 109 2007 339 342 16946305 PMC1785080
  21. [25]Hinds D.A. Barnholt K.E. Mesa R.A. Germ line variants predispose to both JAK2 V617F clonal hematopoiesis and myeloproliferative neoplasms Blood 128 2016 1121 1128 27365426 PMC5085254
  22. [26]Xie M. Lu C. Wang J. Age-related mutations associated with clonal hematopoietic expansion and malignancies Nat Med 20 2014 1472 1478 25326804 PMC4313872
  23. [27]Wang W. Liu W. Fidler T. Macrophage inflammation, erythrophagocytosis, and accelerated atherosclerosis in Jak2 (V617F) mice Circ Res 123 2018 e35 e47 30571460 PMC6309796
  24. [28]Akada H. Yan D. Zou H. Conditional expression of heterozygous or homozygous Jak2V617F from its endogenous promoter induces a polycythemia vera-like disease Blood 115 2010 3589 3597 20197548 PMC2867267
  25. [29]Mullally A. Lane S.W. Ball B. Physiological Jak2V617F expression causes a lethal myeloproliferative neoplasm with differential effects on hematopoietic stem and progenitor cells Cancer Cell 17 2010 584 596 20541703 PMC2909585
  26. [30]Wang J. Hayashi Y. Yokota A. Expansion of EPOR-negative macrophages besides erythroblasts by elevated EPOR signaling in erythrocytosis mouse models Haematologica 103 2018 40 50 29051279 PMC5777189
  27. [31]Xing S. Wanting T.H. Zhao W. Transgenic expression of JAK2V617F causes myeloproliferative disorders in mice Blood 111 2008 5109 5117 18334677 PMC2384138
  28. [32]Georgiades P. Ogilvy S. Duval H. VavCre transgenic mice: a tool for mutagenesis in hematopoietic and endothelial lineages Genesis 34 2002 251 256 12434335
  29. [33]Barde I. Laurenti E. Verp S. Lineage- and stage-restricted lentiviral vectors for the gene therapy of chronic granulomatous disease Gene Ther 18 2011 1087 1097 21544095
  30. [34]Sano S. Wang Y. Evans M.A. Lentiviral CRISPR/Cas9-mediated genome editing for the study of hematopoietic cells in disease models J Vis Exp 152 2019 e59977 PMC7249700 31633690
  31. [35]Wang C.X. Sather B.D. Wang X. Rapamycin relieves lentiviral vector transduction resistance in human and mouse hematopoietic stem cells Blood 124 2014 913 923 24914132 PMC4126331
  32. [36]Gekas C. Graf T. CD41 expression marks myeloid-biased adult hematopoietic stem cells and increases with age Blood 121 2013 4463 4472 23564910
  33. [37]Shi K. Zhao W. Chen Y. Cardiac hypertrophy associated with myeloproliferative neoplasms in JAK2V617F transgenic mice J Hematol Oncol 7 2014 25 24646493 PMC3995113
  34. [38]Arranz L. Sanchez-Aguilera A. Martin-Perez D. Neuropathy of haematopoietic stem cell niche is essential for myeloproliferative neoplasms Nature 512 2014 78 81 25043017
  35. [39]Fleischman A.G. Aichberger K.J. Luty S.B. TNFalpha facilitates clonal expansion of JAK2V617F positive cells in myeloproliferative neoplasms Blood 118 2011 6392 6398 21860020 PMC3236121
  36. [40]Lu X. Levine R. Tong W. Expression of a homodimeric type I cytokine receptor is required for JAK2V617F-mediated transformation Proc Natl Acad Sci U S A 102 2005 18962 18967 16365288 PMC1323216
  37. [41]He W. Qiang M. Ma W. Development of a synthetic promoter for macrophage gene therapy Hum Gene Ther 17 2006 949 959 16972763
  38. [42]Wang Y. Sano S. Oshima K. Wnt5a-mediated neutrophil recruitment has an obligatory role in pressure overload-induced cardiac dysfunction Circulation 140 2019 487 499 31170826 PMC6684855
  39. [43]Wang L. Zhang Y.L. Lin Q.Y. CXCL1-CXCR2 axis mediates angiotensin II-induced cardiac hypertrophy and remodelling through regulation of monocyte infiltration Eur Heart J 39 2018 1818 1831 29514257
  40. [44]Liao X. Shen Y. Zhang R. Distinct roles of resident and nonresident macrophages in nonischemic cardiomyopathy Proc Natl Acad Sci U S A 115 2018 E4661 E4669 29712858 PMC5960298
  41. [45]Patel B. Bansal S.S. Ismahil M.A. CCR2(+) monocyte-derived infiltrating macrophages are required for adverse cardiac remodeling during pressure overload JACC Basic Transl Sci 3 2018 230 244 30062209 PMC6059350
  42. [46]Barbui T. Finazzi G. Falanga A. Myeloproliferative neoplasms and thrombosis Blood 122 2013 2176 2184 23823316
  43. [47]Carobbio A. Finazzi G. Guerini V. Leukocytosis is a risk factor for thrombosis in essential thrombocythemia: interaction with treatment, standard risk factors, and Jak2 mutation status Blood 109 2007 2310 2313 17110452
  44. [48]Landolfi R. Di Gennaro L. Barbui T. Leukocytosis as a major thrombotic risk factor in patients with polycythemia vera Blood 109 2007 2446 2452 17105814
  45. [49]Campbell P.J. MacLean C. Beer P.A. Correlation of blood counts with vascular complications in essential thrombocythemia: analysis of the prospective PT1 cohort Blood 120 2012 1409 1411 22709688 PMC3470936
  46. [50]Lundberg P. Takizawa H. Kubovcakova L. Myeloproliferative neoplasms can be initiated from a single hematopoietic stem cell expressing JAK2-V617F J Exp Med 211 2014 2213 2230 25288396 PMC4203945
  47. [51]Yang Y. Akada H. Nath D. Hutchison R.E. Mohi G. Loss of Ezh2 cooperates with Jak2V617F in the development of myelofibrosis in a mouse model of myeloproliferative neoplasm Blood 127 2016 3410 3423 27081096 PMC4929929
  48. [53]Buscarlet M. Provost S. Zada Y.F. Lineage restriction analyses in CHIP indicate myeloid bias for TET2 and multipotent stem cell origin for DNMT3A Blood 132 2018 277 280 29764839
  49. [54]Mead A.J. Mullally A. Myeloproliferative neoplasm stem cells Blood 129 2017 1607 1616 28159736 PMC5413298
  50. [55]Eaves C.J. Hematopoietic stem cells: concepts, definitions, and the new reality Blood 125 2015 2605 2613 25762175 PMC4440889
  51. [56]Sanjuan-Pla A. Macaulay I.C. Jensen C.T. Platelet-biased stem cells reside at the apex of the haematopoietic stem-cell hierarchy Nature 502 2013 232 236 23934107
  52. [57]Yamamoto R. Morita Y. Ooehara J. Clonal analysis unveils self-renewing lineage-restricted progenitors generated directly from hematopoietic stem cells Cell 154 2013 1112 1126 23993099
  53. [58]Sun J. Ramos A. Chapman B. Clonal dynamics of native haematopoiesis Nature 514 2014 322 327 25296256 PMC4408613
  54. [59]Laurenti E. Gottgens B. From haematopoietic stem cells to complex differentiation landscapes Nature 553 2018 418 426 29364285 PMC6555401
  55. [60]Haas S. Trumpp A. Milsom M.D. Causes and consequences of hematopoietic stem cell heterogeneity Cell Stem Cell 22 2018 627 638 29727678
  56. [61]Chen E. Schneider R.K. Breyfogle L.J. Distinct effects of concomitant Jak2V617F expression and Tet2 loss in mice promote disease progression in myeloproliferative neoplasms Blood 125 2015 327 335 25281607 PMC4287639
  57. [62]McKerrell T. Park N. Chi J. JAK2 V617F hematopoietic clones are present several years before MPN diagnosis and follow different expansion kinetics Blood Adv 1 2017 968 971 29296738 PMC5737599
  58. [63]Libby P. Interleukin-1 beta as a target for atherosclerosis therapy: biological basis of CANTOS and beyond J Am Coll Cardiol 70 2017 2278 2289 29073957 PMC5687846
  59. [64]Nahrendorf M. Myeloid cell contributions to cardiovascular health and disease Nat Med 24 2018 711 720 29867229 PMC7301893
  60. [65]Ridker P.M. Residual inflammatory risk: addressing the obverse side of the atherosclerosis prevention coin Eur Heart J 37 2016 1720 1722 26908943
  61. [66]Swirski F.K. Nahrendorf M. Cardioimmunology: the immune system in cardiac homeostasis and disease Nat Rev Immunol 18 2018 733 744 30228378
  62. [67]Jatiani S.S. Baker S.J. Silverman L.R. Reddy E.P. Jak/STAT pathways in cytokine signaling and myeloproliferative disorders: approaches for targeted therapies Genes Cancer 1 2010 979 993 21442038 PMC3063998
  63. [68]Wolach O. Sellar R.S. Martinod K. Increased neutrophil extracellular trap formation promotes thrombosis in myeloproliferative neoplasms Sci Transl Med 10 2018 eaan8292 29643232 PMC6442466
  64. [69]Savchenko A.S. Borissoff J.I. Martinod K. VWF-mediated leukocyte recruitment with chromatin decondensation by PAD4 increases myocardial ischemia/reperfusion injury in mice Blood 123 2014 141 148 24200682 PMC3879903

Cited by

Sorted by citations

Authors
Sano, S., Wang, Y., Yura, Y., Sano, M., Oshima, K., Yang, Y., Katanasaka, Y., Min, K.-D., Matsuura, S., Ravid, K., Mohi, G., & Walsh, K.
Affiliations
  • University of Virginia (US)
  • Boston University (US)
  • Shizuoka University (JP)
Corresponding author
Walsh, Kenneth
ORCID
Venue
JACC: Basic to Translational Science
Publisher
Elsevier BV
Published
2019-10
Volume
4
Issue
6
Pages
684-697
ISSN
2452-302X (ISSN-L)
DOI
10.1016/j.jacbts.2019.05.013
PMC
PMC6834960
OpenAlex
W2973311260
Cited by
170
References
6
Citations by year
2026: 16 · 2025: 17 · 2024: 21 · 2023: 32 · 2022: 35 · 2021: 28 · 2020: 16 · 2019: 2 · 2018: 1 · 2012: 1
FWCI
14.64
Type
journal article
Language
en
Open access
Licence
Locations
  • JACC Basic to Translational Science (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • American Association of Heart Failure Nurses (17POST33670076)
  • China Scholarship Council
  • University of Virginia
  • National Institutes of Health (HL132564, HL136363, HL138014, HL095685, HL139819, HL141256)
  • Kanae Foundation for the Promotion of Medical Science
  • American Heart Association
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
  • Health Sciences › Medicine › Genetics › Myeloproliferative Neoplasms: Diagnosis and Treatment
  • Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
Keywords
JAK2 V617F mutation, clonal hematopoiesis, heart failure, myeloproliferative neoplasms, myeloid progenitor cells, cardiac inflammation, cardiac remodeling, myocardial infarction, transverse aortic constriction, left anterior descending artery ligation, cardiovascular disease, mouse model

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