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Research Articles

Myeloproliferative Neoplasms Transcriptome Reveals Pro-Inflammatory Signature and Enrichment in Peripheral Blood Monocyte-Related Genes

ORCID Icon, , &
Pages 605-618 | Received 23 Aug 2023, Accepted 19 Jun 2024, Published online: 03 Jul 2024

References

  • Barbui T, Thiele J, Gisslinger H, Kvasnicka HM, Vannucchi AM, Guglielmelli P, et al. The 2016 WHO classification and diagnostic criteria for myeloproliferative neoplasms: document summary and in-depth discussion. Blood Cancer J. 2018;8(2):15. doi:10.1038/s41408-018-0054-y.
  • Greenfield G, McMullin MF, Mills K. Molecular pathogenesis of the myeloproliferative neoplasms. J Hematol Oncol. 2021;14(1):103. doi:10.1186/s13045-021-01116-z.
  • Gleitz HFE, Benabid A, Schneider RK. Still a burning question: the interplay between infammation and fibrosis in myeloproliferative neoplasms. Curr Opin Hematol. 2021;28(5):364–371. doi:10.1097/MOH.0000000000000669.
  • Fleischman AG. Infammation as a driver of clonal evolution in myeloproliferative neoplasm. Mediators Inflamm. 2015;2015:606819. doi:10.1155/2015/606819.
  • Cacemiro M. d C, Cominal JG, Tognon R, Nunes N. d S, Simões BP, Figueiredo-Pontes L. L d, et al. Philadelfia-negative myeloproliferative neoplasms as disorders marked by cytokine modulation. Hematol Transfus Cell Ther. 2018;40(2):120–131. doi:10.1016/j.htct.2017.12.003.
  • Masselli E, Pozzi G, Gobbi G, Merighi S, Gessi S, Vitale M, et al. Cytokine profiling in myeloproliferative neoplasms: overview on phenotype correlation, outcome prediction, and role of genetic variants. Cells. 2020;9(9):2136. doi:10.3390/cells9092136.
  • Richards DM, Hettinger J, Feuerer M. Monocytes and macrophages in cancer: development and functions. Cancer Microenviron. 2013;6(2):179–191. doi:10.1007/s12307-012-0123-x.24.
  • Olingy CE, Dinh HQ, Hedrick CC. Monocyte heterogeneity and functions in cancer. J Leukoc Biol. 2019;106(2):309–322. doi:10.1002/JLB.4RI0818-311R.
  • Bassan VL, Barretto GD, de Almeida FC, Palma PVB, Binelli LS, da Silva JPL, et al. Philadelphia-negative myeloproliferative neoplasms display alterations in monocyte subpopulations frequency and immunophenotype. Med Oncol. 2022;39(12):223. doi:10.1007/s12032-022-01825-6.
  • Skov V, Larsen TS, Thomassen M, Riley CH, Jensen MK, Bjerrum OW, et al. Whole-blood transcriptional profiling of interferon-inducible genes identifies highly upregulated IFI27 in primary myelofibrosis. Eur J Haematol. 2011;87(1):54–60. doi:10.1111/j.1600-0609.2011.01618.x.
  • Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A. 2005;102(43):15545–15550. doi:10.1073/pnas.0506580102.
  • Wong KL, Tai JJ-Y, Wong W-C, Han H, Sem X, Yeap W-H, et al. Gene expression profiling reveals the defining features of the classical, intermediate, and nonclassical human monocyte subsets. Blood. 2011;118(5):e16–e31. doi:10.1182/blood-2010-12-326355.
  • Rusinova I, Forster S, Yu S, Kannan A, Masse M, Cumming H, et al. INTERFEROME v2. 0: an updated database of annotated interferon-regulated genes. Nucleic Acids Res. 2013;41 (database issue):D1040–D1046. doi:10.1093/nar/gks1215.
  • Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W, et al. Limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015;43(7):e47–e47. doi:10.1093/nar/gkv007.
  • Mendez Luque LF, Blackmon AL, Ramanathan G, Fleischman AG. Key role of inflammation in myeloproliferative neoplasms: instigator of disease initiation, progression, and symptoms. Curr Hematol Malig Rep. 2019;14(3):145–153. doi:10.1007/s11899-019-00508-w.
  • Fisher DAC, Fowles JS, Zhou A, Oh ST. Inflammatory pathophysiology as a contributor to myeloproliferative neoplasms. Front Immunol. 2021;12:683401. doi:10.3389/fimmu.2021.683401.
  • Gleitz HFE, Dugourd AJF, Leimkühler NB, Snoeren IAM, Fuchs SNR, Menzel S, et al. Increased CXCL4 expression in hematopoietic cells links inflammation and progression of bone marrow fibrosis in MPN. Blood. 2020;136(18):2051–2064. doi:10.1182/blood.2019004095.
  • Falanga A, Vignoli A, Marchetti M, Russo L, Panova-Noeva M, Balducci D, et al. Impact of V617F JAK2 mutation on monocyte tissue factor and procoagulant activity in patients with essential thrombocythemia (ET) or polycythemia vera (PV). Blood. 2008; 112 (11):3736–3736. doi:10.1182/blood.V112.11.3736.3736.
  • Al-Rifai R, Vandestienne M, Lavillegrand J-R, Mirault T, Cornebise J, Poisson J, et al. JAK2V617F mutation drives vascular resident macrophages toward a pathogenic phenotype and promotes dissecting aortic aneurysm. Nat Commun. 2022;13(1):6592. doi:10.1038/s41467-022-34469-1.
  • Prestipino A, Emhardt AJ, Aumann K, O'Sullivan D, Gorantla SP, Duquesne S, et al. Oncogenic JAK2V617F causes PD-L1 expression, mediating immune escape in myeloproliferative neoplasms. Sci Transl Med. 2018;10(429):eaam7729. doi:10.1126/scitranslmed.aam7729.
  • Jutzi JS, Mullally A. Remodeling the bone marrow microenvironment - a proposal for targeting pro-inflammatory contributors in MPN. Front Immunol. 2020;11:2093. doi:10.3389/fimmu.2020.02093.
  • Goette NP, Lev PR, Heller PG, Kornblihtt LI, Korin L, Molinas FC, et al. Monocyte IL-2Ralpha expression is associated with thrombosis and the JAK2V617F mutation in myeloproliferative neoplasms. Cytokine. 2010;51(1):67–72. doi:10.1016/j.cyto.2010.04.011.
  • Scott MKD, Quinn K, Li Q, Carroll R, Warsinske H, Vallania F, et al. Increased monocyte count as a cellular biomarker for poor outcomes in fibrotic diseases: a retrospective, multicentre cohort study. Lancet Respir Med. 2019;7(6):497–508. doi:10.1016/S2213-2600(18)30508-3.
  • Kreuter M, Lee JS, Tzouvelekis A, Oldham JM, Molyneaux PL, Weycker D, et al. Monocyte count as a prognostic biomarker in patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2021;204(1):74–81. doi:10.1164/rccm.202003-0669OC.
  • Fraser E, Denney L, Antanaviciute A, Blirando K, Vuppusetty C, Zheng Y, et al. Multi-modal characterization of monocytes in idiopathic pulmonary fibrosis reveals a primed type i interferon immune phenotype. Front Immunol. 2021;12:623430. doi:10.3389/fimmu.2021.623430.
  • Boiocchi L, Espinal-Witter R, Geyer JT, Steinhilber J, Bonzheim I, Knowles DM, et al. Development of monocytosis in patients with primary myelofibrosis indicates an accelerated phase of the disease. Mod Pathol. 2013;26(2):204–212. doi:10.1038/modpathol.2012.165.
  • Verstovsek S, Manshouri T, Pilling D, Bueso-Ramos CE, Newberry KJ, Prijic S, et al. Role of neoplastic monocyte-derived fibrocytes in primary myelofibrosis. J Exp Med. 2016;213(9):1723–1740. doi:10.1084/jem.20160283.
  • Maekawa T, Kato S, Kawamura T, Takada K, Sone T, Ogata H, et al. Increased SLAMF7high monocytes in myelofibrosis patients harboring JAK2V617F provide a therapeutic target of elotuzumab. Blood. 2019;134(10):814–825. doi:10.1182/blood.2019000051.
  • Torres DG, Paes J, da Costa AG, Malheiro A, Silva GV, Mourão L. P d S, et al. JAK2 variant signaling: genetic, hematologic and immune implication in chronic myeloproliferative neoplasms. Biomolecules. 2022;12(2):291. doi:10.3390/biom12020291.
  • Morsia E, Torre E, Poloni A, Olivieri A, Rupoli S. Molecular pathogenesis of myeloproliferative neoplasms: from molecular landscape to therapeutic implications. Int J Mol Sci. 2022;23(9):4573. doi:10.3390/ijms23094573.
  • Ertosun MG, Hapil FZ, Osman Nidai O. E2F1 transcription factor and its impact on growth factor and cytokine signaling. Cytokine Growth Factor Rev. 2016;31:17–25. doi:10.1016/j.cytogfr.2016.02.001.
  • Warg LA, Oakes JL, Burton R, Neidermyer AJ, Rutledge HR, Groshong S, et al. The role of the E2F1 transcription factor in the innate immune response to systemic LPS. Am J Physiol Lung Cell Mol Physiol. 2012;303(5):L391–L400. doi:10.1152/ajplung.00369.2011.
  • Liu P, Zhang X, Li Z, Wei L, Peng Q, Liu C, et al. A significant role of transcription factors E2F in inflammation and tumorigenesis of nasopharyngeal carcinoma. Biochem Biophys Res Commun. 2020;524(4):816–824. doi:10.1016/j.bbrc.2020.01.158.
  • Tan Z, Chen M, Peng F, Yang P, Peng Z, Zhang Z, et al. E2F1 as a potential prognostic and therapeutic biomarker by affecting tumor development and immune microenvironment in hepatocellular carcinoma. Transl Cancer Res. 2022;11(8):2713–2732. doi:10.21037/tcr-22-218.
  • Lai HY, Brooks SA, Craver BM, Morse SJ, Nguyen TK, Haghighi N, et al. Defective negative regulation of Toll-like receptor signaling leads to excessive TNF-α in myeloproliferative neoplasm. Blood Adv. 2019;3(2):122–131. doi:10.1182/bloodadvances.2018026450.
  • Fisher DAC, Miner CA, Engle EK, Hu H, Collins TB, Zhou A, et al. Cytokine production in myelofibrosis exhibits differential responsiveness to JAK-STAT, MAP kinase, and NFκB signaling. Leukemia. 2019;33(8):1978–1995. doi:10.1038/s41375-019-0379-y.
  • Pastore F, Bhagwat N, Pastore A, Radzisheuskaya A, Karzai A, Krishnan A, et al. PRMT5 inhibition modulates E2F1 methylation and gene-regulatory networks leading to therapeutic efficacy in JAK2V617F-mutant MPN. Cancer Discov. 2020;10(11):1742–1757. doi:10.1158/2159-8290.CD-20-0026.
  • Barone M, Catani L, Ricci F, Romano M, Forte D, Auteri G, et al. The role of circulating monocytes and JAK inhibition in the infectious-driven inflammatory response of myelofibrosis. Oncoimmunology. 2020;9(1):1782575. doi:10.1080/2162402X.2020.1782575.
  • Subotički T, Mitrović Ajtić O, Živković E, Diklić M, Đikić D, Tošić M, et al. VEGF regulation of angiogenic factors via inflammatory signaling in myeloproliferative neoplasms. Int J Mol Sci. 2021;22(13):6671. doi:10.3390/ijms22136671.
  • Cattaneo D, Iurlo A. Immune dysregulation and infectious complications in MPN patients treated with JAK inhibitors. Front Immunol. 2021;12:750346. doi:10.3389/fimmu.2021.750346.
  • Choi DC, Abu-Zeinah G, Di Giandomenico S, Erdos K, Scandura J. JAK2V617F impairs T cell differentiation in polycythemia vera. Blood. 2022; 140 (Supplement 1):6746–6747. doi:10.1182/blood-2022-167785.
  • Lubbers R, van Essen MF, van Kooten C, Trouw LA. Production of complement components by cells of the immune system. Clin Exp Immunol. 2017;188(2):183–194. doi:10.1111/cei.12952.
  • Kapellos TS, Bonaguro L, Gemünd I, Reusch N, Saglam A, Hinkley ER, et al. Human monocyte subsets and phenotypes in major chronic inflammatory diseases. Front Immunol. 2019;10:2035. doi:10.3389/fimmu.2019.02035.
  • Ramanathan G, Fleischman AG. The microenvironment in myeloproliferative neoplasms. Hematol Oncol Clin North Am. 2021;35(2):205–216. doi:10.1016/j.hoc.2020.11.003.
  • von Brühl M-L, Stark K, Steinhart A, Chandraratne S, Konrad I, Lorenz M, et al. Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo. J Exp Med. 2012;209(4):819–835. doi:10.1084/jem.20112322.
  • Marin Oyarzún CP, Heller PG. Platelets as mediators of thromboinflammation in chronic myeloproliferative neoplasms. Front Immunol. 2019;10:1373. doi:10.3389/fimmu.2019.01373.
  • Skov V, Thomassen M, Kjaer L, Larsen MK, Knudsen TA, Ellervik C, et al. Whole blood transcriptional profiling reveals highly deregulated atherosclerosis genes in Philadelphia-chromosome negative myeloproliferative neoplasms. Eur J Haematol. 2023;111(5):805–814. doi:10.1111/ejh.14081.
  • Jerchel IS, Hoogkamer AQ, Ariës IM, Steeghs EMP, Boer JM, Besselink NJM, et al. RAS pathway mutations as a predictive biomarker for treatment adaptation in pediatric B-cell precursor acute lymphoblastic leukemia. Leukemia. 2018;32(4):931–940. doi:10.1038/leu.2017.303.
  • Carr RM, Vorobyev D, Lasho T, Marks DL, Tolosa EJ, Vedder A, et al. RAS mutations drive proliferative chronic myelomonocytic leukemia via a KMT2A-PLK1 axis. Nat Commun. 2021;12(1):2901. doi:10.1038/s41467-021-23186-w.
  • Ancrile BB, O'Hayer KM, Counter CM. Oncogenic ras-induced expression of cytokines: a new target of anti-cancer therapeutics. Mol Interv. 2008;8(1):22–27. doi:10.1124/mi.8.1.6.
  • Santos FPS, Getta B, Masarova L, Famulare C, Schulman J, Datoguia TS, et al. Prognostic impact of RAS-pathway mutations in patients with myelofibrosis. Leukemia. 2020;34(3):799–810. doi:10.1038/s41375-019-0603-9.
  • Cheon H, Borden EC, Stark GR. Interferons and their stimulated genes in the tumor microenvironment. Semin Oncol. 2014;41(2):156–173. doi:10.1053/j.seminoncol.2014.02.002.
  • von Locquenghien M, Rozalén C, Celià-Terrassa T. Interferons in cancer immunoediting: sculpting metastasis and immunotherapy response. J Clin Invest. 2021;131(1):e143296. doi:10.1172/JCI143296.
  • Cheon HJoo, Wang Y, Wightman SM, Jackson MW, Stark GR. How cancer cells make and respond to interferon-I. Trends Cancer. 2023;9(1):83–92. doi:10.1016/j.trecan.2022.09.003.
  • Bauvois B, Nguyen J, Tang R, Billard C, Kolb J-P. Types I and II interferons upregulate the costimulatory CD80 molecule in monocytes via interferon regulatory factor-1. Biochem Pharmacol. 2009;78(5):514–522. doi:10.1016/j.bcp.2009.05.005.
  • Hasselbalch HC, Silver RT. New perspectives of interferon-alpha2 and inflammation in treating philadelphia-negative chronic myeloproliferative neoplasms. Hemasphere. 2021;5(12):e645. doi:10.1097/HS9.0000000000000645.
  • Skov V, Thomassen M, Kjær L, Ellervik C, Larsen MK, Knudsen TA, et al. Interferon-alpha2 treatment of patients with polycythemia vera and related neoplasms favorably impacts deregulation of oxidative stress genes and antioxidative defense mechanisms. PLoS One. 2022;17(6):e0270669. doi:10.1371/journal.pone.0270669.
  • Fan W, Cao W, Shi J, Gao F, Wang M, Xu L, et al. Contributions of bone marrow monocytes/macrophages in myeloproliferative neoplasms with JAK2V617F mutation. Ann Hematol. 2023;102(7):1745–1759. doi:10.1007/s00277-023-05284-5.

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