The Experts below are selected from a list of 27948 Experts worldwide ranked by ideXlab platform
Alessandro M Vannucchi - One of the best experts on this subject based on the ideXlab platform.
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Therapeutic approaches in Myelofibrosis.
Expert opinion on pharmacotherapy, 2011Co-Authors: Giovanni Barosi, Vittorio Rosti, Alessandro M VannucchiAbstract:Introduction: Myeloproliferative neoplasm (MPN)-associated Myelofibrosis is the most disabling of the classical Philadelphia-negative MPNs. The discovery that a gain-of-function mutation of JAK2 (JAK2V617F) is present in more than 60% of patients with MPN-associated Myelofibrosis has provided a new target for innovative treatment strategies. Areas covered: This review discusses the indications and limitations of conventional therapies employed for the treatment of MPN-associated Myelofibrosis before reviewing the information available for new therapies, including the immunomodulatory and demethylating agents, histone deacethylase, mammalian target of rapamycin (mTOR) and JAK2- inhibitors. The Medline and ASH databases were searched for clinical trials on the medical therapy of MPN-associated Myelofibrosis from early 2000 to December 2010. Expert opinion: Three categories of drugs have proved to have significant activity in MPN-associated Myelofibrosis. Up to a 40% response rate on anemia has been reported...
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From Palliation to Targeted Therapy in Myelofibrosis
The New England Journal of Medicine, 2010Co-Authors: Alessandro M VannucchiAbstract:Myelofibrosis is a very debilitating chronic myeloproliferative neoplasm.1 It may be primary or develop late in the course of essential thrombocythemia or polycythemia vera, the two most common and benign myeloproliferative neoplasms. Patients with Myelofibrosis have shortened survival and a reduced quality of life. The current treatment is palliative and aimed at alleviating symptoms due to splenomegaly, controlling myeloproliferation, and improving anemia and other cytopenias. In this issue of the Journal, Verstovsek et al. report on the results of a phase 1−2 trial of an oral Janus kinase 1 (JAK1) and Janus kinase 2 (JAK2) inhibitor, INCB018424, in advanced Myelofibrosis. . . .
Srdan Verstovsek - One of the best experts on this subject based on the ideXlab platform.
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The evolving understanding of prognosis in post-essential thrombocythemia Myelofibrosis and post-polycythemia vera Myelofibrosis vs primary Myelofibrosis.
Clinical advances in hematology & oncology : H&O, 2019Co-Authors: Lucia Masarova, Srdan VerstovsekAbstract:Myelofibrosis (MF) is the most aggressive of the classic Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs). In some patients with essential thrombocytopenia or polycythemia vera, which are relatively benign MPNs, MF develops as a natural evolution of their disease, resulting in post-essential thrombocythemia Myelofibrosis (PET-MF) or post-polycythemia vera Myelofibrosis (PPV-MF). Presenting with the same clinical features, including debilitating symptoms and signs of bone marrow failure, PET/PPV-MF has traditionally been considered akin to primary Myelofibrosis (PMF). However, recent observations that PET/PPV-MF may be a distinct clinical entity from PMF have triggered efforts to improve prognostication in these diseases. Novel predictive models that incorporate rapidly emerging clinical and molecular data are being developed to improve outcomes in patients with PMF or PET/PPV-MF. This review focuses on the major clinical features and prognostic classification systems used in PMF and PET/PPV-MF.
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Does therapy-related Myelofibrosis exist? Analysis of 1100 Myelofibrosis cases from a single institution.
Journal of Clinical Oncology, 2016Co-Authors: Lucia Masarova, Hagop M Kantarjian, Prithviraj Bose, Naveen Pemmaraju, Naval Daver, Kate J. Newberry, Jorge E. Cortes, Srdan VerstovsekAbstract:e18558Background: The association between prior other malignancies (OM) and Myelofibrosis (MF) as well as the existence of therapy-related Myelofibrosis (t-MF) are largely unknown. We aimed to dete...
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A comprehensive review of pacritinib in Myelofibrosis.
Future oncology (London England), 2015Co-Authors: Srdan Verstovsek, Rami S. KomrokjiAbstract:The first-in-class JAK1/JAK2 inhibitor ruxolitinib inhibits JAK/STAT signaling, inducing durable reductions in splenomegaly and constitutional symptoms in patients with Myelofibrosis. However, the association of ruxolitinib therapy with myelosuppression indicates the continued need for optimal treatment choices in Myelofibrosis. Pacritinib, a dual JAK2 and FLT3 inhibitor, improves disease-related symptoms and signs with manageable gastrointestinal toxicity in patients with Myelofibrosis with splenomegaly and high-risk features, without causing overt myelosuppression, and therefore may provide an important treatment option for a range of patients with Myelofibrosis. This article examines the role of JAK2 and FLT3 signaling in Myelofibrosis and provides an overview of the clinical development of pacritinib as a new therapy for Myelofibrosis.
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safety and efficacy of incb018424 a jak1 and jak2 inhibitor in Myelofibrosis
The New England Journal of Medicine, 2010Co-Authors: Srdan Verstovsek, Jorge Cortesfranco, Edward C Bradley, Ruben A Mesa, Animesh Dev Pardanani, Deborah A. Thomas, Jordan S Fridman, Zeev Estrov, Hagop M Kantarjian, Susan EricksonviitanenAbstract:Background Myelofibrosis is a Philadelphia chromosome–negative myeloproliferative neoplasm associated with cytopenias, splenomegaly, poor quality of life, and shortened survival. About half of patients with Myelofibrosis carry a gain-of-function mutation in the Janus kinase 2 gene (JAK2 V617F) that contributes to the pathophysiology of the disease. INCB018424 is a potent and selective Janus kinase 1 (JAK1) and JAK2 inhibitor. Methods We conducted a phase 1−2 trial of INCB018424 in patients with JAK2 V617F−positive or JAK2 V617F−negative primary Myelofibrosis, post–essential thrombocythemia Myelofibrosis, or post–polycythemia vera Myelofibrosis. Results A total of 153 patients received INCB018424 for a median duration of more than 14.7 months. The initial dose-escalation phase established 25 mg twice daily or 100 mg once daily as maximum tolerated doses, on the basis of reversible thrombocytopenia. A dose-dependent suppression of phosphorylated signal transducer and activator of transcription 3 (STAT3), a ...
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proposed criteria for the diagnosis of post polycythemia vera and post essential thrombocythemia Myelofibrosis a consensus statement from the international working group for Myelofibrosis research and treatment
Leukemia, 2008Co-Authors: G Barosi, Ruben A Mesa, Srdan Verstovsek, Juergen Thiele, Francisco Cervantes, Peter J Campbell, Brigitte Dupriez, Ross L Levine, Francesco Passamonti, Jason GotlibAbstract:Proposed criteria for the diagnosis of post-polycythemia vera and post-essential thrombocythemia Myelofibrosis: a consensus statement from the international working group for Myelofibrosis research and treatment
Kristin Berger - One of the best experts on this subject based on the ideXlab platform.
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Primary Myelofibrosis and its targeted therapy
Annals of Hematology, 2017Co-Authors: Lindsey Shantzer, Kristin BergerAbstract:Primary Myelofibrosis is a unique entity among BCR - ABL -negative myeloproliferative diseases, manifesting as bone marrow fibrosis and pancytopenia. Considerable evidence indicates that genetic and epigenetic abnormalities can result in defective clonal hematopoietic stem cell proliferation in addition to bone marrow microenvironment alteration. The “bad seeds in bad soil” theory illustrates the orchestrating efforts of hematopoietic stem cells, stromal cells, and their surrounding signaling molecules in Myelofibrosis progression and malignancy transformation, though the exact mechanism of Myelofibrosis is still not clear. This study reviews current concepts and questions regarding the pathogenesis of primary Myelofibrosis and discusses the emerging targeted therapy aimed at restoring normal bone marrow environment and halting bone marrow fibrotic deterioration.
Rong Li - One of the best experts on this subject based on the ideXlab platform.
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single cell analyses reveal megakaryocyte biased hematopoiesis in Myelofibrosis and identify mutant clone specific targets
Molecular Cell, 2020Co-Authors: Bethan Psaila, Guanlin Wang, Alba Rodriguezmeira, Rong Li, Elisabeth F Heuston, Lauren Murphy, Ian S Hitchcock, Nikolaos SousosAbstract:Summary Myelofibrosis is a severe myeloproliferative neoplasm characterized by increased numbers of abnormal bone marrow megakaryocytes that induce fibrosis, destroying the hematopoietic microenvironment. To determine the cellular and molecular basis for aberrant megakaryopoiesis in Myelofibrosis, we performed single-cell transcriptome profiling of 135,929 CD34+ lineage− hematopoietic stem and progenitor cells (HSPCs), single-cell proteomics, genomics, and functional assays. We identified a bias toward megakaryocyte differentiation apparent from early multipotent stem cells in Myelofibrosis and associated aberrant molecular signatures. A sub-fraction of Myelofibrosis megakaryocyte progenitors (MkPs) are transcriptionally similar to healthy-donor MkPs, but the majority are disease specific, with distinct populations expressing fibrosis- and proliferation-associated genes. Mutant-clone HSPCs have increased expression of megakaryocyte-associated genes compared to wild-type HSPCs, and we provide early validation of G6B as a potential immunotherapy target. Our study paves the way for selective targeting of the Myelofibrosis clone and illustrates the power of single-cell multi-omics to discover tumor-specific therapeutic targets and mediators of tissue fibrosis.
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single cell analyses reveal aberrant pathways for megakaryocyte biased hematopoiesis in Myelofibrosis and identify mutant clone specific targets
bioRxiv, 2019Co-Authors: Bethan Psaila, Guanlin Wang, Rong Li, Elisabeth F Heuston, Alba Rodriguez Meira, Jennifer OsullivanAbstract:Summary Myelofibrosis is a severe myeloproliferative neoplasm characterised by increased numbers of abnormal bone marrow megakaryocytes that induce progressive fibrosis, destroying the hematopoietic microenvironment. To determine the cellular and molecular basis for aberrant megakaryopoiesis in Myelofibrosis, we performed high-throughput single-cell transcriptome profiling of 50,538 hematopoietic stem/progenitor cells (HSPCs), single-cell proteomics, genomics and functional assays. We identified an aberrant pathway for direct megakaryocyte differentiation from the earliest stages of hematopoiesis in Myelofibrosis and associated aberrant molecular signatures, including surface antigens selectively expressed by JAK2-mutant HSPCs. Myelofibrosis megakaryocyte progenitors were heterogeneous, with distinct expression of fibrosis and proliferation-associated genes and putative therapy targets. We validated the immunoglobulin receptor G6B as a promising JAK2-mutant clone-specific antigen warranting further development as an immunotherapy target. Our study paves the way for selective targeting of the Myelofibrosis clone and more broadly illustrates the power of single-cell multi-omics to discover tumor-specific therapeutic targets and mediators of tissue fibrosis.
Ruben A Mesa - One of the best experts on this subject based on the ideXlab platform.
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effect of ruxolitinib therapy on Myelofibrosis related symptoms and other patient reported outcomes in comfort i a randomized double blind placebo controlled trial
Journal of Clinical Oncology, 2013Co-Authors: Ruben A Mesa, Jason Gotlib, Vikas A Gupta, John Catalano, Michael W Deininger, Alan L Shields, Carole B Miller, Richard T Silver, Moshe TalpazAbstract:Purpose To assess the effects of ruxolitinib on symptom burden and quality of life (QoL) and to evaluate the ability of the modified Myelofibrosis Symptom Assessment Form (MFSAF) v2.0 to measure meaningful changes in Myelofibrosis-related symptoms in patients with Myelofibrosis. Patients and Methods COMFORT-I (Controlled Myelofibrosis Study With Oral JAK Inhibitor Treatment–I) is a double-blind, placebo-controlled phase III study evaluating ruxolitinib in patients with intermediate-2 or high-risk Myelofibrosis. Exploratory analyses were conducted on the following patient-reported outcomes (PROs) assessments: modified MFSAF v2.0 (individual symptoms and Total Symptom Score [TSS]), European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue Scale, and Patient Global Impression of Change (PGIC). Results Patients receiving ruxolitinib experienced improvements in individual myelofibro...
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safety and efficacy of incb018424 a jak1 and jak2 inhibitor in Myelofibrosis
The New England Journal of Medicine, 2010Co-Authors: Srdan Verstovsek, Jorge Cortesfranco, Edward C Bradley, Ruben A Mesa, Animesh Dev Pardanani, Deborah A. Thomas, Jordan S Fridman, Zeev Estrov, Hagop M Kantarjian, Susan EricksonviitanenAbstract:Background Myelofibrosis is a Philadelphia chromosome–negative myeloproliferative neoplasm associated with cytopenias, splenomegaly, poor quality of life, and shortened survival. About half of patients with Myelofibrosis carry a gain-of-function mutation in the Janus kinase 2 gene (JAK2 V617F) that contributes to the pathophysiology of the disease. INCB018424 is a potent and selective Janus kinase 1 (JAK1) and JAK2 inhibitor. Methods We conducted a phase 1−2 trial of INCB018424 in patients with JAK2 V617F−positive or JAK2 V617F−negative primary Myelofibrosis, post–essential thrombocythemia Myelofibrosis, or post–polycythemia vera Myelofibrosis. Results A total of 153 patients received INCB018424 for a median duration of more than 14.7 months. The initial dose-escalation phase established 25 mg twice daily or 100 mg once daily as maximum tolerated doses, on the basis of reversible thrombocytopenia. A dose-dependent suppression of phosphorylated signal transducer and activator of transcription 3 (STAT3), a ...
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proposed criteria for the diagnosis of post polycythemia vera and post essential thrombocythemia Myelofibrosis a consensus statement from the international working group for Myelofibrosis research and treatment
Leukemia, 2008Co-Authors: G Barosi, Ruben A Mesa, Srdan Verstovsek, Juergen Thiele, Francisco Cervantes, Peter J Campbell, Brigitte Dupriez, Ross L Levine, Francesco Passamonti, Jason GotlibAbstract:Proposed criteria for the diagnosis of post-polycythemia vera and post-essential thrombocythemia Myelofibrosis: a consensus statement from the international working group for Myelofibrosis research and treatment
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primary Myelofibrosis pmf post polycythemia vera Myelofibrosis post pv mf post essential thrombocythemia Myelofibrosis post et mf blast phase pmf pmf bp consensus on terminology by the international working group for Myelofibrosis research and treatm
Leukemia Research, 2007Co-Authors: Ruben A Mesa, Srdan Verstovsek, Giovanni Barosi, Francisco Cervantes, Brigitte Dupriez, Ross L Levine, John T Reilly, Mariecaroline Le Boussekerdiles, Martha Wadleigh, Peter J CampbellAbstract:Abstract The International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) is comprised of hematologists, hematopathologists, and laboratory scientists and its main goal is to provide a forum for scientific exchange and collaboration. During its first general meeting in April 2006, the IWG-MRT established uniform treatment response criteria for chronic idiopathic Myelofibrosis (CIMF); also known as agnogenic myeloid metaplasia (AMM), Myelofibrosis with myeloid metaplasia (MMM), and many other names in the hematologic literature. This document summarizes the proceedings from the second meeting of the IWG-MRT, in November 2006, where the group discussed and agreed to standardize the nomenclature referring to CIMF: (i) the term primary Myelofibrosis (PMF) was chosen over several other designations including CIMF, AMM, and MMM, (ii) Myelofibrosis that develops in the setting of either polycythemia vera (PV) or essential thrombocythemia (ET) will be referred to as post-PV MF and post-ET MF, respectively, and (iii) “leukemic” transformation will be recognized as blast phase disease (PMF-BP, post-PV/ET MF in blast phase).
