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https://www.readbyqxmd.com/read/27930945/a-phase-ii-study-of-panobinostat-in-patients-with-primary-myelofibrosis-pmf-and-post-polycythemia-vera-essential-thrombocythemia-myelofibrosis-post-pv-et-mf
#1
John Mascarenhas, Lonette Sandy, Min Lu, James Yoon, Bruce Petersen, David Zhang, Fei Ye, Carrie Newsom, Vesna Najfeld, Tsivia Hochman, Judith D Goldberg, Ronald Hoffman
Myelofibrosis is a chronic and progressive myeloproliferative neoplasm characterized by anemia, splenomegaly, debilitating symptoms and leukemic transformation. Ruxolitinib, an oral JAK1/2 inhibitor, is highly effective in ameliorating systemic symptoms and reducing splenomegaly. Current clinical research is focused on the evaluation of agents based on pre-clinical rationale that can result in disease course modification. Panobinostat is a pan-histone deacetylase inhibitor that has demonstrated clinical activity as a single agent in early phase trials of myelofibrosis...
November 30, 2016: Leukemia Research
https://www.readbyqxmd.com/read/27925044/application-of-prognostic-score-ipset-thrombosis-in-patients-with-essential-thrombocythemia-of-a-brazilian-public-service
#2
Luana Magalhães Navarro, Damila Cristina Trufelli, Debora Rodrigues Bonito, Auro Del Giglio, Patricia Weinschenker Bollmann
Introduction: In patients with essential thrombocythemia (ET), the vascular complications contribute to morbidity and mortality. To better predict the occurrence of thrombotic events, an International Prognostic Score for Thrombosis in Essential Thrombocythemia (IPSET-thrombosis) has recently been proposed. We present the application of this score and compare its results with the usual classification system. Method: We retrospectively evaluated the characteristics and risk factors for thrombosis of 46 patients with a diagnosis of ET seen in the last 6 years at Faculdade de Medicina do ABC (FMABC)...
October 2016: Revista da Associação Médica Brasileira
https://www.readbyqxmd.com/read/27924369/bone-marrow-microvessel-density-and-plasma-angiogenic-factors-in-myeloproliferative-neoplasms-clinicopathological-and-molecular-correlations
#3
Danijela Lekovic, Mirjana Gotic, Radek Skoda, Bojana Beleslin-Cokic, Natasa Milic, Olivera Mitrovic-Ajtic, Ronny Nienhold, Dijana Sefer, Tijana Suboticki, Marijana Buac, Dragana Markovic, Milos Diklic, Vladan P Cokic
Increased angiogenesis in BCR-ABL1 negative myeloproliferative neoplasms (MPNs) has been recognized, but its connection with clinical and molecular markers needs to be defined. The aims of study were to (1) assess bone marrow (BM) angiogenesis measured by microvessel density (MVD) using CD34 and CD105 antibodies; (2) analyze correlation of MVD with plasma angiogenic factors including vascular endothelial growth factor, basic fibroblast growth factor, and interleukin-8; (3) examine the association of MVD with clinicopathological and molecular markers...
December 6, 2016: Annals of Hematology
https://www.readbyqxmd.com/read/27919526/factors-related-to-the-development-of-acquired-von-willebrand-syndrome-in-patients-with-essential-thrombocythemia-and-polycythemia-vera
#4
A Rottenstreich, G Kleinstern, S Krichevsky, D Varon, D Lavie, Y Kalish
OBJECTIVE: We characterized acquired von Willebrand syndrome (AVWS) among essential thrombocythemia (ET) and polycythemia vera (PV) patients. METHODS: A review of patients with ET or PV evaluated for AVWS. RESULTS: Of 116 patients with ET, 64 (55%) developed AVWS; of 57 with PV, 28 (49%) developed AVWS. Median platelet counts of ET and PV patients who developed AVWS were 920×10(9)/L and 679×10(9)/L, respectively (P=0.01). Of patients who developed AVWS, 69...
December 2, 2016: European Journal of Internal Medicine
https://www.readbyqxmd.com/read/27913528/mutations-in-mpns-prognostic-implications-window-to-biology-and-impact-on-treatment-decisions
#5
Jamile M Shammo, Brady L Stein
The last decade has witnessed tremendous scientific advances, ushered in by the JAK2 V617F discovery, contributing to enhanced diagnostic capability and understanding of the biology of myeloproliferative neoplasms (MPNs). Discovery of the calreticulin mutations filled a diagnostic gap; more recent work sheds light on its contribution to disease pathogenesis, and prognosis. Recent studies have also identified novel JAK2 and MPL mutations in patients with essential thrombocythemia and myelofibrosis (MF). Especially in MF, the driver mutational profile has prognostic implications, with additive contributions from the acquisition of additional somatic mutations...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913526/update-from-the-latest-who-classification-of-mpns-a-user-s-manual
#6
Francesco Passamonti, Margherita Maffioli
The 2016 multiparameter World Health Organization (WHO) classification for Philadelphia-negative myeloproliferative neoplasms (MPNs) integrates clinical features, morphology, and genetic data to diagnose polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). The main novelties are: (1) the reduction of the hemoglobin (Hb) level threshold to diagnose PV, now established at 16.5 g/dL for men and 16 g/dL for women (based on the identification of MPN patients with PV-consistent bone marrow [BM] features and a Hb level lower than that established in the 2008 WHO classification for PV); (2) the recognition of prefibrotic/early PMF, distinguishable from ET on the basis of BM morphology, an entity having a higher tendency to develop overt myelofibrosis or acute leukemia, and characterized by inferior survival; (3) the central role of BM morphology in the diagnosis of ET, prefibrotic/early PMF, PMF, and PV with borderline Hb values; megakaryocyte number and morphology (typical in ET, atypical in both PMF forms) accompanied by a new distinction of reticulin fibrosis grade in PMF (grade 1 in prefibrotic/early PMF and grade 2-3 in PMF) constitute diagnostic criteria; and (4) the inclusion of all mutually exclusive MPN driver mutations (JAK2, CALR, and MPL) as major diagnostic criteria in ET and PMF; 10% to 15% of these patients are triple negative, and in these cases the search for an additional clonal marker (eg, mutations in ASXL1, EZH2, TET2, IDH1/IDH2, SRSF2, and SF3B1) is warranted...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27892678/characterization-and-prognosis-significance-of-jak2-v617f-mpl-and-calr-mutations-in-philadelphia-negative-myeloproliferative-neoplasms
#7
Roongrudee Singdong, Teerapong Siriboonpiputtana, Takol Chareonsirisuthigul, Adcharee Kongruang, Nittaya Limsuwanachot, Tanasan Sirirat, Suporn Chuncharunee, Budsaba Rerkamnuaychoke
Background: The discovery of somatic acquired mutations of JAK2 (V617F) in Philadelphia-negative myeloproliferative neoplasms (Ph-negative MPNs) including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) has not only improved rational disease classification and prognostication but also brings new understanding insight into the pathogenesis of diseases. Dosage effects of the JAK2 (V617F) allelic burden in Ph-negative MPNs may partially influence clinical presentation, disease progression, and treatment outcome...
January 10, 2016: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/27892526/comprehensive-gene-expression-meta-analysis-and-integrated-bioinformatic-approaches-reveal-shared-signatures-between-thrombosis-and-myeloproliferative-disorders
#8
Prabhash Kumar Jha, Aatira Vijay, Anita Sahu, Mohammad Zahid Ashraf
Thrombosis is a leading cause of morbidity and mortality in patients with myeloproliferative disorders (MPDs), particularly polycythemia vera (PV) and essential thrombocythemia (ET). Despite the attempts to establish a link between them, the shared biological mechanisms are yet to be characterized. An integrated gene expression meta-analysis of five independent publicly available microarray data of the three diseases was conducted to identify shared gene expression signatures and overlapping biological processes...
November 28, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27880982/safety-and-efficacy-of-ruxolitinib-in-splanchnic-vein-thrombosis-associated-with-myeloproliferative-neoplasms
#9
Lisa Pieri, Chiara Paoli, Umberto Arena, Fabio Marra, Fabio Mori, Mery Zucchini, Stefano Colagrande, Alessandro Castellani, Arianna Masciulli, Vittorio Rosti, Valerio De Stefano, Silvia Betti, Guido Finazzi, Maria Luisa Ferrari, Elisa Rumi, Marco Ruggeri, Ilaria Nichele, Paola Guglielmelli, Rajmonda Fjerza, Carmela Mannarelli, Tiziana Fanelli, Lucia Merli, Giuditta Corbizi Fattori, Margherita Massa, Giuseppe Cimino, Alessandro Rambaldi, Giovanni Barosi, Mario Cazzola, Tiziano Barbui, Alessandro M Vannucchi
Splanchnic vein thrombosis (SVT) is one of the vascular complications of myeloproliferative neoplasms (MPN). We designed a phase 2 clinical trial to evaluate safety and efficacy of ruxolitinib in reducing splenomegaly and improving disease-related symptoms in patients with MPN-associated SVT. Patients, diagnosed with myelofibrosis in 12 cases, polycythemia vera in 5 and essential thrombocythemia in 4, received ruxolitinib for 24 weeks in the core study period. Spleen volume was assessed by magnetic resonance imaging (MRI) and splanchnic vein circulation by echo-Doppler analysis...
November 23, 2016: American Journal of Hematology
https://www.readbyqxmd.com/read/27875935/jak2-mpl-and-calr-mutations-in-chinese-han-patients-with-essential-thrombocythemia
#10
Jing Wang, Biao Zhang, Bing Chen, Rong-Fu Zhou, Qi-Guo Zhang, Juan Li, Yong-Gong Yang, Min Zhou, Xiao-Yan Shao, Yong Xu, Xi-Hui Xu, Jian Ouyang, Jingyan Xu, Qing Ye
BACKGROUND: Mutations in Janus kinase 2 (JAK2), myeloproliferative leukemia (MPL), and CALR are highly relevant to Philadelphia chromosome (Ph)-negative myeloproliferative neoplasms. METHODS: Assessing the prevalence of molecular mutations in Chinese Han patients with essential thrombocythemia (ET), and correlating their mutational profile with disease characteristics/phenotype. RESULTS: Of the 110 subjects studied, 62 carried the JAK2 V617F mutation, 21 had CALR mutations, one carried an MPL (W515) mutation, and 28 had non-mutated JAK2, CALR, and MPL (so-called triple-negative ET)...
November 22, 2016: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/27875375/management-of-venous-thromboembolism-in-myeloproliferative-neoplasms
#11
Tiziano Barbui, Valerio De Stefano
PURPOSE OF REVIEW: Venous thromboembolism is frequent in chronic myeloproliferative neoplasms (MPN). The current strategy for its management includes cytoreductive therapy and antithrombotic prophylaxis, but many issues remain uncertain. In this review, the risk factors and prevention of recurrences will be discussed. RECENT FINDINGS: Around one-third of patients with polycythemia vera and essential thrombocythemia experience a major thrombosis at diagnosis or during follow-up...
November 21, 2016: Current Opinion in Hematology
https://www.readbyqxmd.com/read/27870387/primary-myelofibrosis-2017-update-on-diagnosis-risk-stratification-and-management
#12
Ayalew Tefferi
: Disease overview: Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) characterized by stem cell-derived clonal myeloproliferation that is often but not always accompanied by JAK2, CALR or MPL mutation, abnormal cytokine expression, bone marrow fibrosis, anemia, splenomegaly, extramedullary hematopoiesis (EMH), constitutional symptoms, cachexia, leukemic progression and shortened survival. DIAGNOSIS: Diagnosis is based on bone marrow morphology...
December 2016: American Journal of Hematology
https://www.readbyqxmd.com/read/27858230/efficacy-and-safety-of-jak-inhibitor-inc424-in-patients-with-primary-and-post-polycythemia-vera-or-post-essential-thrombocythemia-myelofibrosis-in-the-chinese-population
#13
Xin Du, Daobin Zhou
A phase II study (A2202) was performed to evaluate the efficacy and safety of JAK inhibitor ruxolitinib in 63 Chinese MF patients. Ruxolitinib was given twice a day (bid) at a starting dose of 15 mg (n = 25) or 20 mg (n = 38) based on a baseline platelet count. About 94.7% of the patients achieved a reduction in spleen size, 27.0% of which exhibited significant reduction (≥ 35%) at week 24. Significant improvement in debilitating constitutional symptoms, as assessed by MFSAF v2.0, was observed in patients treated with ruxolitinib...
November 17, 2016: Frontiers of Medicine
https://www.readbyqxmd.com/read/27856474/treatment-of-essential-thrombocythemia
#14
(no author information available yet)
No abstract text is available yet for this article.
November 17, 2016: Blood
https://www.readbyqxmd.com/read/27855276/detection-of-calr-and-mpl-mutations-in-low-allelic-burden-jak2-v617f-essential-thrombocythemia
#15
Fabrice Usseglio, Nathalie Beaufils, Anne Calleja, Sophie Raynaud, Jean Gabert
Myeloproliferative neoplasms are clonal hematopoietic stem cell disorders characterized by aberrant proliferation and an increased tendency toward leukemic transformation. The genes JAK2, MPL, and CALR are frequently altered in these syndromes, and their mutations are often a strong argument for diagnosis. We analyzed the mutational profiles of these three genes in a cohort of 164 suspected myeloproliferative neoplasms. JAK2 V617F mutation was detected by real-time PCR, whereas high-resolution melting analysis followed by Sanger sequencing were used for searching for mutations in JAK2 exon 12, CALR, and MPL...
November 14, 2016: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/27851358/1723-acquired-von-willebrand-disease-in-essential-thrombocythemia
#16
Kathryn Kaye Berlin, Patrick Foy
No abstract text is available yet for this article.
December 2016: Critical Care Medicine
https://www.readbyqxmd.com/read/27822101/the-danish-national-chronic-myeloid-neoplasia-registry
#17
REVIEW
Marie Bak, Else Helene Ibfelt, Thomas Stauffer Larsen, Dorthe Rønnov-Jessen, Niels Pallisgaard, Ann Madelung, Lene Udby, Hans Carl Hasselbalch, Ole Weis Bjerrum, Christen Lykkegaard Andersen
AIM: The Danish National Chronic Myeloid Neoplasia Registry (DCMR) is a population-based clinical quality database, introduced to evaluate diagnosis and treatment of patients with chronic myeloid malignancies. The aim is to monitor the clinical quality at the national, regional, and hospital departmental levels and serve as a platform for research. STUDY POPULATION: The DCMR has nationwide coverage and contains information on patients diagnosed at hematology departments from January 2010 onward, including patients with essential thrombocythemia, polycythemia vera, myelofibrosis, unclassifiable myeloproliferative neoplasms, chronic myelomonocytic leukemia, and chronic myeloid leukemia...
2016: Clinical Epidemiology
https://www.readbyqxmd.com/read/27807369/calreticulin-mutant-mice-develop-essential-thrombocythemia-that-is-ameliorated-by-the-jak-inhibitor-ruxolitinib
#18
K Shide, T Kameda, T Yamaji, M Sekine, N Inada, A Kamiunten, K Akizuki, K Nakamura, T Hidaka, Y Kubuki, H Shimoda, A Kitanaka, A Honda, A Sawaguchi, H Abe, T Miike, H Iwakiri, Y Tahara, M Sueta, S Hasuike, S Yamamoto, K Nagata, K Shimoda
Mutations of calreticulin (CALR) are detected in 25-30% of patients with essential thrombocythemia (ET) or primary myelofibrosis and cause frameshifts that result in proteins with a novel C-terminal. We demonstrate that CALR mutations activated signal transducer and activator of transcription 5 (STAT5) in 293T cells in the presence of thrombopoietin receptor (MPL). Human megakaryocytic CMK11-5 cells and erythroleukemic F-36P-MPL cells with knocked-in CALR mutations showed increased growth and acquisition of cytokine-independent growth, respectively, accompanied by STAT5 phosphorylation...
November 29, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27801320/-analysis-of-prognostic-factors-in-chinese-patients-with-post-polycythemia-vera-myelofibrosis-and-post-essential-thrombocythemia-myelofibrosis
#19
M Chen, Z F Xu, J Q Xu, B Li, P H Zhang, T J Qin, Y Zhang, J Y Wang, H L Zhang, L W Fang, L J Pan, N B Hu, S Q Qu, Z J Xiao
Objective: To evaluate the performances of the prognostic scoring systems devised for primary myelofibrosis(PMF)and the new developed MYSEC- PM(Mysec Prognostic Model)and investigate the risk factors in Chinese patients with post-polycythemia vera myelofibrosis and post-essential thrombocythemia myelofibrosis(post- PV/ET MF). The most widely used prognostic scoring systems in PMF included the International Prognostic Scoring System(IPSS), dynamic International Prognostic Scoring System(DIPSS), refined DIPSS(DIPSS plus), modified IPSS for Chinese(IPSS-Chinese), and modified DIPSS for Chinese(DIPSS- Chinese)...
October 14, 2016: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/27787922/bone-health-in-patients-with-hematopoietic-disorders-of-bone-marrow-origin-systematic-review-and-meta-analysis
#20
Kieran Steer, Mariya Stavnichuk, Martin Morris, Svetlana V Komarova
Blood cell production and bone homeostasis are physically interlinked systems that exhibit active cross-talk. We examined how bone health is affected in patients with hematopoietic disorders due to abnormal proliferation of bone marrow cells. The electronic databases Medline, Embase, PubMed, BIOSIS Previews, Web of Science, and Cochrane were searched for studies presenting numerical values for trabecular bone volume or bone mineral density in control and patients with hematopoietic disorders. We identified 5 studies for beta-thalassemia, 6 for sickle cell anemia, 2 for polycythemia vera and essential thrombocythemia, 3 for chronic myelogenous leukemia, 6 for myelofibrosis, 5 for multiple myeloma, and 4 studies each for systemic mastocytosis, lymphocytic leukemia, and hemochromatosis...
October 27, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
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