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Essential Thrombocythemia

Prithviraj Bose, Srdan Verstovsek
INTRODUCTION: Primary myelofibrosis (PMF) is the least common but the most aggressive of the classic Philadelphia chromosome-negative myeloproliferative neoplasms. Survival is much shorter in PMF than in polycythemia vera (PV) or essential thrombocythemia (ET). Post-PV/ET myelofibrosis (MF) is clinically indistinguishable from PMF and approached similarly. AREAS COVERED: Current pharmacologic therapy of MF revolves around the Janus kinase 1/2 (JAK1/2) inhibitor ruxolitinib, which dramatically improves constitutional symptoms and splenomegaly in the majority of patients, and improves overall survival (OS)...
October 22, 2016: Expert Opinion on Pharmacotherapy
M Haider, Y C Elala, N Gangat, C A Hanson, A Tefferi
No abstract text is available yet for this article.
October 21, 2016: Blood Cancer Journal
Lasse Kjær, Sabrina Cordua, Morten O Holmström, Mads Thomassen, Torben A Kruse, Niels Pallisgaard, Thomas S Larsen, Karin de Stricker, Vibe Skov, Hans C Hasselbalch
Discovery of somatic mutations in the calreticulin gene (CALR) has identified a subgroup of Philadelphia-negative chronic myeloproliferative neoplasms (MPN) with separate haematological characteristics and prognosis. CALR mutations serve as novel markers both of diagnostic value and as targets for monitoring molecular responses during therapy. Interferon-α (IFN) selectively targets the malignant clone in a subset of MPN patients and can induce both haematological and molecular remissions in CALR mutated essential thrombocythemia (ET) patients...
2016: PloS One
Prithviraj Bose, Srdan Verstovsek
The Philadelphia chromosome negative myeloproliferative neoplasms (MPN) mainly comprise polycythemia vera (PV), essential thrombocythemia (ET) and myelofibrosis (MF, primary or post-PV/ET). Therapy in PV and ET focuses on minimizing thrombosis and bleeding risk, while in MF, prolongation of survival is an important goal. Different cytoreductive agents are employed in high risk PV and ET, while the JAK inhibtior ruxolitinib is the cornerstone of therapy in MF. Histone deacetylase inhibitors (HDACi) are pleiotropic agents with diverse epigenetic and non-epigenetic actions, selectively in transformed cells...
October 18, 2016: Expert Opinion on Investigational Drugs
Steven Wang, Jie Yan, Guangde Zhou, Rebecca Heintzelman, J Steve Hou
Myeloproliferative neoplasms (MPNs) are hematopoietic malignancies characterized by unchecked proliferation of differentiated myeloid cells. The most common BCR-ABL1-negative MPNs are polycythemia vera, essential thrombocythemia, and primary myelofibrosis. The discovery of JAK2 V617F mutation has improved our understanding of the molecular basis of MPN. The high frequency of JAK2 mutation in MPN makes JAK2 mutation testing an essential diagnostic tool and potential therapeutic target for MPN. Here, we present a rare case of a 34-year-old patient who was initially diagnosed with acute myeloid leukemia (AML) with mutated NPM1...
2016: Case Reports in Hematology
Maya Koren-Michowitz, Noa Lavi, Martin H Ellis, Alessandro M Vannucchi, Ruben Mesa, Claire N Harrison
Extreme thrombocytosis (ExT) has been associated with an increased bleeding risk in myeloproliferative neoplasm (MPN) patients and is included in the high risk category in treatment guidelines. Treatment of patients with ExT has not been studied in prospective trials. To study physicians' approaches to ExT, we distributed a web based questionnaire with clinical case scenarios to 202 members of MPN working groups. Cases included low thrombotic risk essential thrombocythemia (ET) with either JAK2V617F or CALR mutation, polycythemia vera with ExT either with or without leukocytosis, an ET patient needing urgent orthopedic surgery, and a poorly controlled ET patient with acute cerebral venous sinus thrombosis...
October 13, 2016: Annals of Hematology
S Farmer, V V Shanbhogue, S Hansen, C I Stahlberg, H Vestergaard, A P Hermann, H Frederiksen
: In this cross-sectional study of 45 patients with myeloproliferative neoplasms, we found no evidence of secondary osteoporosis. INTRODUCTION: Patients with essential thrombocythemia (ET) and polycythaemia vera (PV) are at increased risk of fractures but the underlying mechanisms have not been settled. We conducted a study to assess bone mineral density, microarchitecture, estimated bone strength and global bone turnover in 45 patients with ET or PV. METHODS: Patients were evaluated in a cross-sectional study with dual energy X-ray absorptiometry (DXA) at the hip and spine; high-resolution peripheral quantitative computed tomography (HR-pQCT) at the distal radius and distal tibia; and biochemical markers of bone turnover including pro-collagen type 1 N-terminal pro-peptide, osteocalcin, C-terminal cross-linking telopeptide of type 1 collagen and bone-specific alkaline phosphatase...
October 13, 2016: Osteoporosis International
Sabine Blum, Filipe Martins, Lorenzo Alberio
The discovery of JAK2 V617F mutation in the mid-2000s started to fill the gap between clinical presentation of polycythemia vera (PV), first described by Vaquez at the end of the 19th century, and spontaneous erythroid colony formation, reported by Prchal and Axelrad in the mid-1970s. The knowledge on this mutation brought an important insight to our understanding of PV pathogenesis and led to a revision of the World Health Organization diagnostic criteria in 2008. JAK-STAT is a major signaling pathway implicated in survival and proliferation of hematopoietic precursors...
2016: Journal of Blood Medicine
Daniel Xia, Robert P Hasserjian
Polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) are myeloproliferative neoplasms characterized by recurrent somatic mutations in JAK2, CALR, and MPL. This short review addresses 1) the spectrum of mutations seen in PV, ET, and PMF, 2) the emerging genotype-phenotype correlations, 3) the current role of molecular testing in disease classification and management, and 4) several important considerations for selecting an appropriate molecular test. In our view, sequential testing algorithms and simultaneous assessment of multiple mutations by next-generation sequencing are both valid approaches to testing...
October 11, 2016: American Journal of Hematology
K-H Lim, Y-C Chang, Y-H Chiang, H-C Lin, C-Y Chang, C-S Lin, L Huang, W-T Wang, C Gon-Shen Chen, W-C Chou, Y-Y Kuo
CALR mutations are identified in about 30% of JAK2/MPL-unmutated myeloproliferative neoplasms (MPNs) including essential thrombocythemia (ET) and primary myelofibrosis. Although the molecular pathogenesis of CALR mutations leading to MPNs has been studied using in vitro cell lines models, how mutant CALR may affect developmental hematopoiesis remains unknown. Here we took advantage of the zebrafish model to examine the effects of mutant CALR on early hematopoiesis and model human CALR-mutated MPNs. We identified three zebrafish genes orthologous to human CALR, referred to as calr, calr3a and calr3b...
October 7, 2016: Blood Cancer Journal
Z C Li, H J Fu, Z M Wang, S Yang, H Z Xu
In this study, we investigated the correlation between the JAK2V617F mutation and thrombosis in patients with myeloproliferative neoplasm (MPN) using real-time fluorescence quantitative PCR. The incidence of thrombus was monitored and blood and coagulation were routinely assayed in patients with MPN. The JAK2V617F mutation was found in 8/68 individuals in the control group (11.8%); it was expressed in 44/68 patients with MPN (64.7%), suggesting that the rate of this mutation was significantly higher in patients with MPN than that in the control group...
August 29, 2016: Genetics and Molecular Research: GMR
Nariyoshi Matsumoto, Sayaka Mori, Hiroo Hasegawa, Daisuke Sasaki, Hayato Mori, Kazuto Tsuruda, Daisuke Imanishi, Yoshitaka Imaizumi, Tomoko Hata, Norihito Kaku, Kousuke Kosai, Naoki Uno, Yasushi Miyazaki, Katsunori Yanagihara
INTRODUCTION: Recently, novel calreticulin (CALR) mutations were discovered in Janus kinase 2 (JAK2) non-mutated myelofibrosis (PMF) and essential thrombocythemia (ET) cases, with a frequency of 60-80%. We examined clinical correlations and CALR mutation frequency in our myeloproliferative neoplasms (MPN) cases, and introduce an effective test method for use in clinical practice. METHODS: We examined 177 samples previously investigated for the JAK2 mutation for differential diagnosis of MPN...
November 1, 2016: Clinica Chimica Acta; International Journal of Clinical Chemistry
Ruben A Mesa, Carole B Miller, Maureen Thyne, James Mangan, Sara Goldberger, Salman Fazal, Xiaomei Ma, Wendy Wilson, Dilan C Paranagama, David G Dubinski, Ahmad Naim, Shreekant Parasuraman, John Boyle, John O Mascarenhas
BACKGROUND: This analysis of the myeloproliferative neoplasm (MPN) Landmark survey evaluated gaps between patient perceptions of their disease management and physician self-reported practices. METHODS: The survey included 813 patient respondents who had MPNs (myelofibrosis [MF], polycythemia vera [PV], or essential thrombocythemia [ET]) and 457 hematologist/oncologist respondents who treated patients with these conditions. RESULTS: Greater proportions of physician respondents reported using prognostic risk classifications (MF, 83%; PV, 59%; ET, 77%) compared with patient recollections (MF, 54%; PV, 17%; ET, 31%)...
September 30, 2016: Cancer
Juli-Anne Gardner, Jason D Peterson, Scott A Turner, Barbara L Soares, Courtney R Lancor, Luciana L Dos Santos, Prabhjot Kaur, Deborah L Ornstein, Gregory J Tsongalis, Francine B de Abreu
OBJECTIVES: To describe three methods used to screen for frameshift mutations in exon 9 of the CALR gene. METHODS: Genomic DNA from 47 patients was extracted from peripheral blood and bone marrow using the EZ1 DNA Blood Kit (Qiagen, Valencia, CA) and quantified by the Quant-iT PicoGreen dsDNA Assay Kit (Invitrogen, San Diego, CA). After clinical history, cytogenetics, and molecular tests, patients were diagnosed with either clonal or nonclonal hematologic diseases...
October 2016: American Journal of Clinical Pathology
Laila Nomani, Juraj Bodo, Xiaoxian Zhao, Lisa Durkin, Sanam Loghavi, Eric D Hsi
OBJECTIVES: Mutations in CALR (calreticulin) have been discovered in 50% to 80% of JAK2 (Janus kinase 2) and MPL (myeloproliferative leukemia protein) wild-type patients with Philadelphia-negative myeloproliferative neoplasm (MPNs). We evaluate the performance of a monoclonal antibody for immunohistochemical detection of CALR mutations. METHODS: A computerized archival search was performed for cases of non-chronic myeloid leukemia (CML) MPNs with available CALR and JAK2 V617F mutational analysis data...
October 2016: American Journal of Clinical Pathology
Jennifer L Hou, Oluwakemi Onajin, Naseema Gangat, Mark D P Davis, Alexandra P Wolanskyj
No abstract text is available yet for this article.
August 9, 2016: Leukemia & Lymphoma
Shinsuke Takagi, Kazuhiro Masuoka, Naoyuki Uchida, Mineo Kurokawa, Hirohisa Nakamae, Kazunori Imada, Koji Iwato, Tatsuo Ichinohe, Yoshiko Atsuta, Akiyoshi Takami, Shingo Yano
To clarify the outcome of allogeneic hematopoietic cell transplantation (HCT) for leukemic transformation (LT) preceded by Philadelphia chromosome-negative (Ph-neg) myeloproliferative neoplasms (MPNs), we conducted a retrospective study using the national registry database of the Japan Society for Hematopoietic Cell Transplantation. From 2000 to 2013, 39 patients underwent their first allogeneic HCT with related bone marrow or peripheral blood stem cells (n = 8), unrelated bone marrow (n = 15), and unrelated umbilical cord blood (n = 16)...
September 22, 2016: Biology of Blood and Marrow Transplantation
Vikas Gupta, Ruben A Mesa, Michael W N Deininger, Candido E Rivera, Shireen Sirhan, Carrie Baker Brachmann, Helen Collins, Jun Kawashima, Yan Xin, Srdan Verstovsek
Momelotinib, a small-molecule inhibitor of Janus kinase 1 and Janus kinase 2, has demonstrated efficacy in myelofibrosis patients with 300 mg, once-daily dosing. This open-label, nonrandomized, phase 1/2 study evaluated the safety and therapeutic benefit of momelotinib with twice-daily dosing. A total of 61 subjects with primary myelofibrosis or post-polycythemia vera/post-essential thrombocythemia myelofibrosis with intermediate- or high-risk disease received momelotinib. A phase 1 dose escalation identified 200 mg twice daily as the optimal dose to be expanded in phase 2...
September 15, 2016: Haematologica
Marine M Tanashyan, Polina I Kuznetsova, Alla A Shabalina, Anton A Raskurazhev, Olga V Lagoda, Irina N Subortseva, Anait L Melikyan
BACKGROUND: Disturbances of microcirculation play a significant role in the development and progression of both acute and chronic cerebrovascular diseases (CVD) and may be associated with different hemogram abnormalities. One of the reasons of the prothrombogenic state of the endothelium is the increase in the number of blood corpuscles leading to (non-Ph) myeloproliferative disorders (MPD) including essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PM)...
September 7, 2016: Cerebrovascular Diseases Extra
Maria Helena Ornellas, Monique De França Silva, Cristiana Solza, Stella Beatriz Sampaio De Lucena Gonçalves, Liliane Silva De Almeida, Jackline De Paula Ayres-Silva, Taís Leite Seixas, Elenice Ferreira Bastos, Thomas Liehr, Gilda Alves
Myelodysplastic syndrome (MDS) cases comprise a heterogeneous group of hematological disorders that are characterized by impaired hematopoiesis, with cytopenias of different grades and risk of developing acute myeloid leukemia. MDS may rarely be associated with thrombocytosis. In such cases, myelodysplasia and myeloproliferative disorders may overlap, making correct diagnosis difficult. We herein describe a case of MDS with thrombocytosis, Janus kinase 2 gene mutation-positive and Perls' staining-negative, which was initially classified as essential thrombocythemia (ET)...
September 2016: Molecular and Clinical Oncology
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