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mutation in the general population: myeloproliferative neoplasm development and progression rate","volume":"99","author":"C Nielsen","year":"2014","journal-title":"Haematologica"},{"issue":"39","key":"ref78","doi-asserted-by":"crossref","first-page":"16616","DOI":"10.1073\/pnas.0908107106","article-title":"A progenitor cell origin of myeloid malignancies","volume":"106","author":"H Haeno","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"41","key":"ref79","doi-asserted-by":"crossref","first-page":"17604","DOI":"10.1073\/pnas.1009117107","article-title":"A mathematical framework to determine the temporal sequence of somatic genetic events in cancer","volume":"107","author":"CS Attolini","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref80","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/nrc1295","article-title":"Dynamics of cancer progression","volume":"4","author":"F Michor","year":"2004","journal-title":"Nature Reviews Cancer"},{"key":"ref81","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1038\/nature03669","article-title":"Dynamics of chronic myeloid leukaemia","volume":"435","author":"F Michor","year":"2005","journal-title":"Nature"},{"issue":"17","key":"ref82","doi-asserted-by":"crossref","first-page":"7950","DOI":"10.1158\/0008-5472.CAN-05-0564","article-title":"A validated mathematical model of cell-mediated immune response to tumor growth","volume":"65","author":"LG De Pillis","year":"2005","journal-title":"Cancer Research"},{"issue":"17","key":"ref83","doi-asserted-by":"crossref","first-page":"2854","DOI":"10.1200\/JCO.2007.15.2421","article-title":"Mathematical models of cancer stem cells","volume":"26","author":"F Michor","year":"2008","journal-title":"J Clin Oncol"},{"issue":"7\u20138","key":"ref84","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1016\/j.mcm.2010.03.057","article-title":"Characterization of stem cells using mathematical models of multistage cell lineages","volume":"53","author":"T Stiehl","year":"2011","journal-title":"Mathematical and Computer Modelling"},{"issue":"1","key":"ref85","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1051\/mmnp\/20127199","article-title":"Mathematical Modeling of Leukemogenesis and Cancer Stem Cell Dynamics","volume":"7","author":"T Stiehl","year":"2012","journal-title":"Math Model Nat Phenom"},{"issue":"8","key":"ref86","doi-asserted-by":"crossref","first-page":"e71128","DOI":"10.1371\/journal.pone.0071128","article-title":"A mathematical model of cancer stem cell driven tumor initiation: implications of niche size and loss of homeostatic regulatory mechanisms","volume":"8","author":"SN Gentry","year":"2013","journal-title":"Plos One"},{"issue":"4","key":"ref87","doi-asserted-by":"crossref","first-page":"e1003599","DOI":"10.1371\/journal.pcbi.1003599","article-title":"Feedback Signals in Myelodysplastic Syndromes: Increased Self-Renewal of the Malignant Clone Suppresses Normal Hematopoiesis","volume":"10","author":"T Walenda","year":"2014","journal-title":"PLoS Comput Biol"},{"issue":"6","key":"ref88","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1158\/0008-5472.CAN-14-2508","article-title":"Cell Division Patterns in Acute Myeloid Leukemia Stem-like Cells Determine Clinical Course: A Model to Predict Patient Survival","volume":"75","author":"T Stiehl","year":"2015","journal-title":"Cancer Research"},{"key":"ref89","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/s13062-016-0154-1","article-title":"Emergence of heterogeneity in acute leukemias","volume":"11","author":"T Stiehl","year":"2016","journal-title":"Biology Direct"},{"key":"ref90","first-page":"1727","article-title":"A mathematic model for relating the drug sensitivity of tumors to their spontaneous mutation rate","volume":"63","author":"JH Goldie","year":"1979","journal-title":"Cancer Treatment Reports"},{"key":"ref91","first-page":"923","article-title":"Quantitative model for multiple levels of drug resistance in clinical tumors","volume":"67","author":"JH Goldie","year":"1983","journal-title":"Cancer Treatment Reports"},{"issue":"12","key":"ref92","doi-asserted-by":"crossref","first-page":"2603","DOI":"10.1634\/stemcells.2006-0136","article-title":"Successful therapy must eradicate cancer stem cells","volume":"24","author":"D Dingli","year":"2006","journal-title":"Stem Cells"},{"key":"ref93","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1016\/S0895-7177(03)00133-X","article-title":"The dynamics of an optimal controlled tumor model: a case study","volume":"37","author":"LG De Pillis","year":"2003","journal-title":"Mathematical and computer modelling"},{"issue":"6","key":"ref94","first-page":"1","article-title":"Complex dynamics in a mathematical model of tumor growth with time delays in cell proliferation","volume":"2","author":"M Saleem","year":"2012","journal-title":"International Journal of Scientific and Research Publications"},{"issue":"3","key":"ref95","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1093\/imammb\/dqt006","article-title":"Bifurcation Analysis of an Existing Mathematical Model Reveals Novel Treatment Strategies and Suggests Potential Cure for Type 1 Diabetes","volume":"31","author":"KH Nielsen","year":"2014","journal-title":"Mathematical Medicine and Biology"},{"key":"ref96","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1093\/imammb\/dqs026","article-title":"Mathematical modelling of cytokine-mediated inflammation in rheumatoid arthritis","volume":"30","author":"M Baker","year":"2013","journal-title":"Mathematical Medicine and Biology"},{"key":"ref97","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1007\/s11538-009-9468-9","article-title":"General Model of Inflammation","volume":"72","author":"MC Herald","year":"2010","journal-title":"Bulletin of Mathematical Biology"},{"key":"ref98","doi-asserted-by":"crossref","first-page":"1953","DOI":"10.1007\/s11538-014-9987-x","article-title":"The Resolution of Inflammation: A Mathematical Model of Neutrophil and Macrophage Interactions","volume":"76","author":"JL Dunster","year":"2014","journal-title":"Bull Math Biol"},{"issue":"1","key":"ref99","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1137\/1035003","article-title":"Qualitative Theory of Compartmental Systems","volume":"35","author":"JA Jacquez","year":"1993","journal-title":"SIAM Review"},{"key":"ref100","doi-asserted-by":"crossref","first-page":"14931","DOI":"10.1073\/pnas.0607006103","article-title":"The age incidence of chronic myeloid leukemia can be explained by a one-mutation model","volume":"103","author":"F Michor","year":"2006","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref101","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1093\/genetics\/148.4.1483","article-title":"The mutation rate and cancer","volume":"148","author":"AL Jackson","year":"1998","journal-title":"Genetics"},{"key":"ref102","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1096\/fj.02-0752rev","article-title":"Oxidative DNA damage: mechanisms, mutation, and disease","volume":"17","author":"MS Cooke","year":"2003","journal-title":"FASEB J"},{"key":"ref103","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.mrfmmm.2010.03.007","article-title":"Chronic inflammation and mutagenesis","volume":"690","author":"LR Ferguson","year":"2010","journal-title":"Mutat Res"},{"issue":"2","key":"ref104","doi-asserted-by":"crossref","first-page":"e100490","DOI":"10.1371\/journal.pgen.1004901","article-title":"Inflammation-Induced Cell Proliferation Potentiates DNA Damage-Induced Mutations in Vivo","volume":"11","author":"O Kiraly","year":"2015","journal-title":"Plos Genet"},{"issue":"10","key":"ref105","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1038\/nri3062","article-title":"Inflammatory modulation of hematopoietic stem cells: viewing the hematopoietc stem cell as a foundation for the immune response","volume":"11","author":"KY King","year":"2014","journal-title":"Nat Rev Immmunol"},{"key":"ref106","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1056\/NEJMra1300575","article-title":"Fibrosis\u2014A Common Pathway to Organ Injury and Fibrosis","volume":"372","author":"DC Rockey","year":"2015","journal-title":"N Engl J Med"},{"issue":"26","key":"ref107","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1056\/NEJM198612253152606","article-title":"Tumors: wounds that do not heal, Similarities between tumor stroma generation and wound healing","volume":"315","author":"HF Dvorak","year":"1986","journal-title":"N Engl J Med"},{"issue":"1","key":"ref108","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1158\/2326-6066.CIR-14-0209","article-title":"Tumors: wounds that do not heal-redux","volume":"3","author":"HF Dvorak","year":"2015","journal-title":"Cancer Immunology Research"},{"key":"ref109","doi-asserted-by":"crossref","first-page":"3254","DOI":"10.1038\/srep03254","article-title":"Inflammation and Immune System Activation in Aging: A Mathematical Approach","volume":"3","author":"JB Nikas","year":"2013","journal-title":"Scientific Reports"},{"issue":"3","key":"ref110","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1093\/imammb\/dqt006","article-title":"Bifurcation analysis of an existing mathematical model reveals novel treatment strategies and suggests potential cure for type 1 diabetes","volume":"31","author":"KH Nielsen","year":"2014","journal-title":"Math Med Biol"},{"key":"ref111","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.jtbi.2012.09.025","article-title":"Mathematical model of colitis-associated colon cancer","volume":"317","author":"WC Lo","year":"2013","journal-title":"J Theor Biol"},{"issue":"5","key":"ref112","doi-asserted-by":"crossref","first-page":"2785","DOI":"10.1182\/blood-2007-06-095703","article-title":"Host genetic variation contributes to phenotypic diversity in myeloproliferative disorders","volume":"111","author":"A Pardanani","year":"2008","journal-title":"Blood"},{"issue":"4","key":"ref113","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1038\/ng.342","article-title":"A germline JAK2 SNP is associated with predisposition to the development of JAK2(V617F)-positive myeloproliferative neoplasms","volume":"41","author":"O Kilpivaara","year":"2009","journal-title":"Nat Genet"},{"issue":"4","key":"ref114","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1038\/ng.334","article-title":"JAK2 haplotype is a major risk factor for the development of myeloproliferative neoplasms","volume":"41","author":"AV Jones","year":"2009","journal-title":"Nat Genet"},{"issue":"4","key":"ref115","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1038\/ng.341","article-title":"A common JAK2 haplotype confers susceptibility to myeloproliferative neoplasms","volume":"41","author":"D Olcaydu","year":"2009","journal-title":"Nat Genet"},{"key":"ref116","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1182\/asheducation-2011.1.208","article-title":"Genetic and epigenetic complexity in myeloproliferative neoplasms","author":"NC Cross","year":"2011","journal-title":"Hematology Am Soc Hematol Educ Program"},{"key":"ref117","doi-asserted-by":"crossref","first-page":"6691","DOI":"10.1038\/ncomms7691","article-title":"Genetic variation at MECOM, TERT, JAK2 and HBS1L-MYB predisposes to myeloproliferative neoplasms","volume":"6","author":"W Tapper","year":"2015","journal-title":"Nat Commun"},{"issue":"8","key":"ref118","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1038\/ng.175","article-title":"Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease","volume":"40","author":"JC Barrett","year":"2008","journal-title":"Nat Genet"},{"issue":"1\u20132","key":"ref119","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.mrfmmm.2010.01.017","article-title":"Genetic factors in chronic inflammation: single nucleotide polymorphisms in the STAT-JAK pathway, susceptibility to DNA damage and Crohn's disease in a New Zealand population","volume":"690","author":"LR Ferguson","year":"2010","journal-title":"Mutat Res"},{"issue":"1","key":"ref120","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1111\/j.1365-2141.1994.tb04970.x","article-title":"Transforming growth factor-beta and megakaryocytes in the pathogenesis of idiopathic myelofibrosis","volume":"88","author":"MC Martyre","year":"1994","journal-title":"Br J Haematol"},{"issue":"17","key":"ref121","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1056\/NEJM200004273421706","article-title":"Myelofibrosis with myeloid metaplasia","volume":"342","author":"A Tefferi","year":"2000","journal-title":"N Engl J Med"},{"issue":"13","key":"ref122","doi-asserted-by":"crossref","first-page":"2991","DOI":"10.1182\/blood-2011-12-380113","article-title":"Demand-adapted regulation of early hematopoiesis in infection and inflammation","volume":"119","author":"H Takizawa","year":"2012","journal-title":"Blood"},{"key":"ref123","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1159\/000296507","article-title":"Monocytes and macrophages regulate immunity through dynamic networks of survival and cell death","volume":"2","author":"A Parihar","year":"2010","journal-title":"J Innate Immun"},{"issue":"1","key":"ref124","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1182\/blood-2016-01-636399","article-title":"Metastasis: new functional implications of platelets and megakaryocytes","volume":"128","author":"R Leblanc","year":"2016","journal-title":"Blood"},{"issue":"10","key":"ref125","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1016\/j.leukres.2014.07.006","article-title":"The platelet-cancer loop in myeloproliferative cancer. Is thrombocythemia an enhancer of cancer invasiveness and metastasis in essential thrombocythemia, polycythemia vera and myelofibrosis?","volume":"38","author":"HC Hasselbalch","year":"2014","journal-title":"Leuk Res"},{"issue":"6","key":"ref126","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1586\/ehm.11.63","article-title":"A new era for IFN-\u03b1 in the treatment of Philadelphia-negative chronic myeloproliferative neoplasms","volume":"4","author":"HC Hasselbalch","year":"2011","journal-title":"Expert Rev Hematol"},{"issue":"1","key":"ref127","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1586\/ehm.12.69","article-title":"Interferon and the treatment of polycythemia vera, essential thrombocythemia and myelofibrosis","volume":"6","author":"RT Silver","year":"2013","journal-title":"Expert Rev Hematol"},{"key":"ref128","first-page":"1","article-title":"Minimal residual disease after long-term interferon-alpha2 treatment: a report on hematological, molecular and histomorphological response patterns in 10 patients with essential thrombocythemia and polycythemia vera","author":"C Rank","year":"2015","journal-title":"Leuk Lymphoma"},{"issue":"4","key":"ref129","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1038\/leu.2015.326","article-title":"Interferon-alpha for the therapy of myeloproliferative neoplasms: targeting the malignant clone","volume":"30","author":"JJ Kiladjian","year":"2016","journal-title":"Leukemia"},{"issue":"2","key":"ref130","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1586\/17474086.2013.876356","article-title":"Perspectives on the impact of JAK-inhibitor therapy upon inflammation-mediated comorbidities in myelofibrosis and related neoplasms","volume":"7","author":"HC Hasselbalch","year":"2014","journal-title":"Expert Rev Hematol"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0183620","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T07:55:45Z","timestamp":1750838145000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0183620"}},"subtitle":[],"editor":[{"given":"Pal Bela","family":"Szecsi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2017,8,31]]},"references-count":130,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2017,8,31]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0183620","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,8,31]]}}}