The immune landscape in BCR-ABL negative myeloproliferative neoplasms: inflammation, infections and opportunities for immunotherapy
TLDR
The role of inflammation in disease pathogenesis, susceptibility to infection and emerging strategies for therapeutic immune modulation in negative myeloproliferative neoplasms (MPNs) are discussed in this article.Abstract:
Breakpoint cluster region-Abelson (BCR-ABL) negative myeloproliferative neoplasms (MPNs) are chronic myeloid neoplasms initiated by the acquisition of gene mutation(s) in a haematopoietic stem cell, leading to clonal expansion and over-production of blood cells and their progenitors. MPNs encompass a spectrum of disorders with overlapping but distinct molecular, laboratory and clinical features. This includes polycythaemia vera, essential thrombocythaemia and myelofibrosis. Dysregulation of the immune system is key to the pathology of MPNs, supporting clonal evolution, mediating symptoms and resulting in varying degrees of immunocompromise. Targeting immune dysfunction is an important treatment strategy. In the present review, we focus on the immune landscape in patients with MPNs - the role of inflammation in disease pathogenesis, susceptibility to infection and emerging strategies for therapeutic immune modulation. Further detailed work is required to delineate immune perturbation more precisely in MPNs to determine how and why vulnerability to infection differs between clinical subtypes and to better understand how inflammation results in a competitive advantage for the MPN clone. These studies may help shed light on new designs for disease-modifying therapies.read more
Citations
More filters
Journal ArticleDOI
Prediction of Survival and Prognosis Migration from Gold-Standard Scores in Myelofibrosis Patients Treated with Ruxolitinib Applying the RR6 Prognostic Model in a Monocentric Real-Life Setting
Andrea Duminuco,Antonella Nardo,Bruno Garibaldi,Calogero Vetro,A Longo,Cesarina Giallongo,Francesco Di Raimondo,Giuseppe A. Palumbo +7 more
TL;DR: In this paper , a clinical prognostic score named RR6 (Response to Ruxolitinib after 6 months) was proposed to determine survival in patients affected by myelofibrosis.
Journal ArticleDOI
Philadelphia-negative myeloproliferative neoplasms display alterations in monocyte subpopulations frequency and immunophenotype
Vitor Leonardo Bassan,Gabriel Dessotti Barretto,Felipe Campos de Almeida,Patricia Vianna Bonini Palma,Larissa Sarri Binelli,João Paulo Lettieri da Silva,Caroline Fontanari,Ricardo Cardoso Castro,Lorena Lôbo de Figueiredo Pontes,Fabiani Gai Frantz,Fabíola Attié de Castro +10 more
TL;DR: In this paper , the frequency and immunophenotype of peripheral blood monocyte subpopulations in patients with polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (MF) were evaluated.
Journal ArticleDOI
Perspective: Pivotal translational hematology and therapeutic insights in chronic myeloid hematopoietic stem cell malignancies
Tariq I. Mughal,Naveen Pemmaraju,Rafael Bejar,Robert Peter Gale,Prithviraj Bose,Jean-Jacques Kiladjian,Josef T. Prchal,Daniel J. Royston,Daniel A. Pollyea,Peter Valent,Tim H. Brümmendorf,Tomasz Skorski,Mrinal M. Patnaik,Valeria Santini,Pierre Fenaux,Nicole Kucine,Srdan Verstovsek,Ruben A. Mesa,Tiziano Barbui,Giuseppe Saglio,Richard A. Van Etten +20 more
TL;DR: Some of the pivotal translational hematology and therapeutic insights in chronic myeloid malignancies diseases are focused on.
Journal ArticleDOI
Mutation-Driven S100A8 Overexpression Confers Aberrant Phenotypes in Type 1 CALR-Mutated MPN
Ying-Hsuan Wang,Ying-Ju Chen,Yi-Hua Lai,Ming-Chung Wang,Yi-Yang Chen,Yu-Ying Wu,Yao-Ren Yang,H.-Y. Tsou,Chian-Pei Li,Chia Chen Hsu,Cih-En Huang,Chih-Cheng Chen +11 more
TL;DR: In this paper , the expression of S100a8 was investigated in myeloproliferative neoplasms (MPN) and showed that S100A8 could be regulated by STAT3 based on luciferase reporter assay complemented with inhibitor treatment.
References
More filters
Journal ArticleDOI
Oncology Meets Immunology: The Cancer-Immunity Cycle
TL;DR: Emerging clinical data suggest that cancer immunotherapy is likely to become a key part of the clinical management of cancer and may be more effective in combination with agents that target other steps of the cycle.
Journal ArticleDOI
T cell exhaustion
TL;DR: Advances in the molecular delineation of T cell exhaustion are clarifying the underlying causes of this state of differentiation and also suggest promising therapeutic opportunities.
Journal ArticleDOI
Molecular and cellular insights into T cell exhaustion
E. John Wherry,Makoto Kurachi +1 more
TL;DR: Recent advances that provide a clearer molecular understanding of T cell exhaustion are reviewed and reveal new therapeutic targets for persisting infections and cancer.
Journal ArticleDOI
A Double-Blind, Placebo-Controlled Trial of Ruxolitinib for Myelofibrosis
Srdan Verstovsek,Ruben A. Mesa,Jason Gotlib,Richard S. Levy,Vikas Gupta,John F. DiPersio,John Catalano,Michael W. Deininger,Michael W. Deininger,Carole B. Miller,Richard T. Silver,Moshe Talpaz,Elliott F. Winton,Jimmie H. Harvey,Murat O. Arcasoy,Elizabeth O. Hexner,Roger M. Lyons,Ronald Paquette,Azra Raza,Kris Vaddi,Susan Erickson-Viitanen,Iphigenia L. Koumenis,William Sun,Victor Sandor,Hagop M. Kantarjian +24 more
TL;DR: Ruxolitinib provided significant clinical benefits in patients with myel ofibrosis by reducing spleen size, ameliorating debilitating myelofibrosis-related symptoms, and improving overall survival.
Journal ArticleDOI
Safety and Efficacy of INCB018424, a JAK1 and JAK2 Inhibitor, in Myelofibrosis
Srdan Verstovsek,Hagop M. Kantarjian,Ruben A. Mesa,Animesh Pardanani,Jorge Cortes-Franco,Deborah A. Thomas,Zeev Estrov,Jordan S. Fridman,Edward C Bradley,Susan Erickson-Viitanen,Kris Vaddi,Richard S. Levy,Ayalew Tefferi +12 more
TL;DR: INCB018424 was associated with marked and durable clinical benefits in patients with myelofibrosis for whom no approved therapies existed, and clinical benefits were associated with a marked diminution of levels of circulating inflammatory cytokines that are commonly elevated in myel ofibrosis.