Inflammatory Microenvironment and Specific T Cells in Myeloproliferative Neoplasms: Immunopathogenesis and Novel Immunotherapies.
Vincenzo Nasillo,Giovanni Riva,Ambra Paolini,Fabio Forghieri,Luca Roncati,Beatrice Lusenti,Monica Maccaferri,Andrea Messerotti,Valeria Pioli,Andrea Gilioli,Francesca Bettelli,Davide Giusti,Patrizia Barozzi,Ivana Lagreca,Rossana Maffei,Roberto Marasca,Leonardo Potenza,Patrizia Comoli,Rossella Manfredini,Antonino Maiorana,Enrico Tagliafico,Mario Luppi,Tommaso Trenti +22 more
TLDR
Recent insights in the immunological dysfunctions contributing to the pathogenesis of Philadelphia-negative myeloproliferative neoplasms are focused on and the potential impact of related immunotherapeutic approaches are outlined.Abstract:
The Philadelphia-negative myeloproliferative neoplasms (MPNs) are malignancies of the hematopoietic stem cell (HSC) arising as a consequence of clonal proliferation driven by somatically acquired driver mutations in discrete genes (JAK2, CALR, MPL). In recent years, along with the advances in molecular characterization, the role of immune dysregulation has been achieving increasing relevance in the pathogenesis and evolution of MPNs. In particular, a growing number of studies have shown that MPNs are often associated with detrimental cytokine milieu, expansion of the monocyte/macrophage compartment and myeloid-derived suppressor cells, as well as altered functions of T cells, dendritic cells and NK cells. Moreover, akin to solid tumors and other hematological malignancies, MPNs are able to evade T cell immune surveillance by engaging the PD-1/PD-L1 axis, whose pharmacological blockade with checkpoint inhibitors can successfully restore effective antitumor responses. A further interesting cue is provided by the recent discovery of the high immunogenic potential of JAK2V617F and CALR exon 9 mutations, that could be harnessed as intriguing targets for innovative adoptive immunotherapies. This review focuses on the recent insights in the immunological dysfunctions contributing to the pathogenesis of MPNs and outlines the potential impact of related immunotherapeutic approaches.read more
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Multiparametric Flow Cytometry for MRD Monitoring in Hematologic Malignancies: Clinical Applications and New Challenges.
Giovanni Riva,Vincenzo Nasillo,Anna Maria Ottomano,Giuliano Bergonzini,Ambra Paolini,Fabio Forghieri,Beatrice Lusenti,Patrizia Barozzi,Ivana Lagreca,Stefania Fiorcari,Silvia Martinelli,Rossana Maffei,Roberto Marasca,Leonardo Potenza,Patrizia Comoli,Rossella Manfredini,Enrico Tagliafico,Tommaso Trenti,Mario Luppi +18 more
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Myeloid-Derived Suppressor Cells and Mesenchymal Stem/Stromal Cells in Myeloid Malignancies.
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Defining disease modification in myelofibrosis in the era of targeted therapy
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Multiparametric MRI to quantify disease and treatment response in mice with myeloproliferative neoplasms
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References
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Journal ArticleDOI
The bone marrow niche for haematopoietic stem cells
TL;DR: The haematopoietic stem cell niche remains incompletely defined and beset by competing models, and outstanding questions concern the cellular complexity of the niche, the role of the endosteum and functional heterogeneity among perivascular microenvironments.
Journal ArticleDOI
Somatic Mutations of Calreticulin in Myeloproliferative Neoplasms
Thorsten Klampfl,Heinz Gisslinger,Ashot S. Harutyunyan,Harini Nivarthi,Elisa Rumi,Jelena D. Milosevic,Nicole C.C. Them,Tiina Berg,Bettina Gisslinger,Daniela Pietra,Doris Chen,Gregory I. Vladimer,Klaudia Bagienski,Chiara Milanesi,Ilaria Carola Casetti,Emanuela Sant'Antonio,Virginia Valeria Ferretti,Chiara Elena,Fiorella Schischlik,Ciara Cleary,Melanie Six,Martin Schalling,Andreas Schönegger,Christoph Bock,Luca Malcovati,Cristiana Pascutto,Giulio Superti-Furga,Mario Cazzola,Robert Kralovics +28 more
TL;DR: Most patients with essential thrombocythemia or primary myelofibrosis that was not associated with a JAK2 or MPL alteration carried a somatic mutation in CALR, and patients with mutated CALR had a lower risk ofThrombosis and longer overall survival than patients with mutations in J AK2.
Journal ArticleDOI
Somatic CALR Mutations in Myeloproliferative Neoplasms with Nonmutated JAK2
Jyoti Nangalia,Charles E. Massie,E J Baxter,Francesca L. Nice,Gunes Gundem,David C. Wedge,Edward Avezov,Juan Li,Karoline Kollmann,David G. Kent,Athar Aziz,Anna L. Godfrey,Jonathon Hinton,Inigo Martincorena,P Van Loo,Amy V. Jones,Paola Guglielmelli,P. S. Tarpey,Heather P. Harding,J.D. Fitzpatrick,C.T. Goudie,Christina A. Ortmann,Stephen J. Loughran,Keiran Raine,David R. Jones,Adam Butler,Jon W. Teague,Sarah O’Meara,Stuart McLaren,M. Bianchi,Yvonne Silber,D. Dimitropoulou,David Bloxham,L. Mudie,Mark Maddison,Bruce W. S. Robinson,Clodagh Keohane,Cathy MacLean,Kate Hill,Kim Orchard,Sudhir Tauro,Ming-Qing Du,Mel Greaves,David G. Bowen,Brian J. P. Huntly,Claire N. Harrison,Nicholas C.P. Cross,David Ron,Alessandro M. Vannucchi,Elli Papaemmanuil,Peter J. Campbell,Anthony R. Green +51 more
TL;DR: Somatic mutations in the endoplasmic reticulum chaperone CALR were found in a majority of patients with myeloproliferative neoplasms with nonmutated JAK2, a finding consistent with its role as an initiating mutation in some patients.
Journal ArticleDOI
JAK2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis.
Linda M. Scott,Wei Tong,Ross L. Levine,Michael A. Scott,Philip A. Beer,Michael R. Stratton,P. Andrew Futreal,Wendy N. Erber,Mary Frances McMullin,Claire N. Harrison,Alan J. Warren,Alan J. Warren,D. Gary Gilliland,D. Gary Gilliland,Harvey F. Lodish,Anthony R. Green,Anthony R. Green +16 more
TL;DR: Four somatic gain-of-function mutations affecting JAK2 exon 12 define a distinctive myeloproliferative syndrome that affects patients who currently receive a diagnosis of polycythemia vera or idiopathic erythrocytosis.
Journal ArticleDOI
MPL515 mutations in myeloproliferative and other myeloid disorders: a study of 1182 patients
Animesh Pardanani,Ross L. Levine,Terra L. Lasho,Yana Pikman,Ruben A. Mesa,Martha Wadleigh,David P. Steensma,Michelle A. Elliott,Alexandra P. Wolanskyj,William J. Hogan,Rebecca F. McClure,Mark R. Litzow,D. Gary Gilliland,Ayalew Tefferi +13 more
TL;DR: In this paper, a gain-of-function MPL mutation, MPLW515L, was described in patients with JAK2V617F-negative myelofibrosis with myeloid metaplasia (MMM).