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myeloprolifeative neoplasm

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https://www.readbyqxmd.com/read/29056075/an-updated-review-of-the-jak1-2-inhibitor-ruxolitininb-in-the-philadelphia-negative-myeloproliferative-neoplasms
#1
Natalia Curto-Garcia, Claire N Harrison
Ruxolitinib (Rux), a JAK1/2 inhibitor, has been approved for patients with myelofibrosis and in polycythemia vera with inadequate response/intolerance to hydroxycarbamide. Studies have demonstrated that Rux improves disease-related symptoms and splenomegaly. A late emerging observation from two Phase III trials was that Rux was associated with survival advantage in comparison with placebo or other available therapies in myelofibrosis. Important data suggest that for polycythemia vera Rux improved control of blood counts...
October 23, 2017: Future Oncology
https://www.readbyqxmd.com/read/29047144/mecom-hbs1l-myb-thrb-rarb-jak2-and-tert-polymorphisms-defining-the-genetic-predisposition-to-myeloproliferative-neoplasms-a-study-on-939-patients
#2
Adrian P Trifa, Claudia Bănescu, Anca S Bojan, Cristian M Voina, Ștefana Popa, Simona Vișan, Alina D Ciubean, Florin Tripon, Delia Dima, Viola M Popov, Ștefan C Vesa, Mihaela Andreescu, Tünde Török-Vistai, Romeo G Mihăilă, Nicoleta Berbec, Ioan Macarie, Andrei Coliță, Maria Iordache, Alina C Cătană, Marius F Farcaș, Ciprian Tomuleasa, Kinga Vasile, Cristina Truică, Adriana Todincă, Lavinia Pop-Muntean, Raluca Manolache, Horia Bumbea, Ana-Maria Vlădăreanu, Mihaela Gaman, Cristina M Ciufu, Radu A Popp
Polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) are classical myeloproliferative neoplasms (MPN), characterized by specific somatic mutations in JAK2, CALR or MPL genes. JAK2 46/1 and TERT rs2736100 polymorphisms are known to significantly predispose to MPN. This study aimed to establish the additional contribution of the recently described MECOM rs2201862, HBS1L-MYB rs9376092 and THRB-RARB rs4858647 polymorphisms to the occurrence of MPN. These three polymorphisms, along with JAK2 46/1 and TERT rs2736100 were genotyped in 939 MPN patients (454 with ET, 337 with PV and 148 with PMF) and 483 controls...
October 19, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/29042365/ruxolitinib-induced-defects-in-dna-repair-cause-sensitivity-to-parp-inhibitors-in-myeloproliferative-neoplasms
#3
Margaret Nieborowska-Skorska, Silvia Maifrede, Yashodhara Dasgupta, Katherine Sullivan, Sylwia Flis, Bac Viet Le, Martyna Solecka, Elizaveta A Belyaeva, Lucia Kubovcakova, Morgan Nawrocki, Martin Kirschner, Huaqing Zhao, Josef T Prchal, Katarzyna Piwocka, Alison R Moliterno, Mariusz Wasik, Steffen Koschmieder, Tony R Green, Radek C Skoda, Tomasz Skorski
Myeloproliferative neoplasms (MPNs) often carry JAK2(V617F), MPL(W515L), or CALR(del52) mutations. Current treatment options for MPNs include cytoreduction by hydroxyurea and JAK1/2 inhibition by ruxolitinib, both of which are not curative. We show here that cell lines expressing JAK2(V617F), MPL(W515L) or CALR(del52) accumulated reactive oxygen species-induced DNA double-strand breaks (DSBs) and were modestly sensitive to poly-ADP-ribose polymerase (PARP) inhibitors olaparib and BMN673. At the same time primary MPN cell samples from individual patients displayed a high degree of variability in the sensitivity to these drugs...
October 17, 2017: Blood
https://www.readbyqxmd.com/read/29040257/current-challenges-in-the-management-of-essential-thrombocythemia
#4
Ariel Kleman, Arun K Singavi, Laura C Michaelis
Essential thrombocythemia (ET), an uncommon blood cancer, is one of the classic myeloproliferative neoplasms, a category that also includes polycythemia vera and primary myelofibrosis. All 3 diseases are clonal hematopoietic stem cell disorders. Since 2005, when scientists discovered a molecular aberration driving clonal hematopoiesis in polycythemia vera, our understanding of the genomic underpinnings of these conditions has increased rapidly. Over the last decades, primary prevention of thrombotic and hemorrhagic complications has improved the lives of patients with ET, and the ability to characterize the disease by the presence or absence of molecular mutations has lent precision to our prognostic models...
October 2017: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/29037480/linking-energy-sensing-to-suppression-of-jak-stat-signalling-a-potential-route-for-repurposing-ampk-activators
#5
REVIEW
Claire Speirs, Jamie J L Williams, Kirsten Riches, Ian P Salt, Timothy M Palmer
Exaggerated Janus kinase-signal transducer and activator of transcription (JAK-STAT) signalling is key to the pathogenesis of pro-inflammatory disorders, such as rheumatoid arthritis and cardiovascular diseases. Mutational activation of JAKs is also responsible for several haematological malignancies, including myeloproliferative neoplasms and acute lymphoblastic leukaemia. Accumulating evidence links adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK), an energy sensor and regulator of organismal and cellular metabolism, with the suppression of immune and inflammatory processes...
October 13, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29027642/familial-mpn-predisposition
#6
REVIEW
Tsewang Tashi, Sabina Swierczek, Josef T Prchal
Chronic myeloproliferative neoplasms (MPN) characteristically arise from a somatic mutation in the pluripotent hematopoietic stem cell, and most common recurring mutations are in the JAK2, CALR, and cMPL genes. However, these mutations are not founder mutations, but mainly drive the disease phenotype and a pre-existing germline predisposition has been long speculated, but has not been clearly defined to date. Genome-wide association studies in family clusters of MPN have identified a number of genetic variants that are associated with increased germline risk for developing clonal MPN...
October 13, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/29027146/correction-to-jsh-guideline-for-tumors-of-hematopoietic-and-lymphoid-tissues-lukemia-4-chronic-myelogenous-leukemia-cml-myeloproliferative-neoplasms-mpn
#7
Noriko Usui
In the original publication of this article, the "Acknowledgements" was not included and it is given below for your reading.
October 12, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/29025582/a-novel-trip11-flt3-fusion-in-a-patient-with-a-myeloid-lymphoid-neoplasm-with-eosinophilia
#8
Alfred Chung, Yanli Hou, Robert S Ohgami, Ann Von Gehr, Dianna G Fisk, Krishna M Roskin, Xu Li, Linda Gojenola, Charles D Bangs, Daniel A Arber, Andrew Z Fire, Athena M Cherry, James L Zehnder, Jason Gotlib, Jason D Merker
FLT3 fusions are associated with myeloid and lymphoid neoplasms with eosinophilia. We describe a patient presenting with clinicopathologic features of both chronic eosinophilic leukemia, not otherwise specified (CEL, NOS) and systemic mastocytosis (SM). The bone marrow demonstrated a myeloproliferative neoplasm with eosinophilia and aggregates of atypical mast cells. Cytogenetic analysis revealed a t(13;14)(q12;q32), which was subsequently molecularly characterized as a novel TRIP11-FLT3 rearrangement. A KIT D816V mutation was also identified...
October 2017: Cancer Genetics
https://www.readbyqxmd.com/read/29024842/peritoneal-carcinomatosis-like-implants-of-extramedullary-hematopoiesis-an-insolite-occurrence-during-splenectomy-for-myelofibrosis
#9
Marco Casaccia, Rosario Fornaro, Marco Frascio, Denise Palombo, Cesare Stabilini, Emma Firpo, Ezio Gianetta
INTRODUCTION: Primary myelofibrosis (MF) is a myeloproliferative neoplasm that results in debilitating constitutional symptoms, splenomegaly, and cytopenias. In patients with symptomatic splenomegaly, splenectomy remains a viable treatment option for MF patients with medically refractory symptomatic splenomegaly that precludes the use of ruxolitinib. CASE PRESENTATION: We present the clinical case of a patient who was admitted to our Department to perform a splenectomy in MF as a therapeutic step prior to an allogeneic stem cell transplantation (ASCT)...
October 5, 2017: International Journal of Surgery Case Reports
https://www.readbyqxmd.com/read/29024710/determination-of-complex-subclonal-structures-of-haematological-malignancies-by-multiplexed-genotyping-of-blood-progenitor-colonies
#10
Francesca L Nice, Charlie E Massie, Thorsten Klampfl, Anthony R Green
Current next generation sequencing (NGS) technologies allow unprecedented insights into the mutational profiles of tumours. Recent studies in myeloproliferative neoplasms have further demonstrated that not only the mutational profile, but also the order in which these mutations are acquired is relevant for our understanding of the disease. Our ability to assign mutation order from NGS data alone, is however limited. Here we present a strategy of highly multiplexed genotyping of burst forming unit-erythroid (BFU-E) colonies based on NGS results to assess subclonal tumour structure...
October 9, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/29024542/the-relative-bioavailability-food-effect-and-drug-interaction-with-omeprazole-of-momelotinib-tablet-formulation-in-healthy-subjects
#11
Yan Xin, Lixin Shao, Julie Maltzman, Dimitrios Stefanidis, Jeffrey Hemenway, Thomas Tarnowski, Wei Deng, Jeffrey A Silverman
Momelotinib is a potent and selective small-molecule inhibitor of JAK1/2 that is under investigation for the treatment of myeloproliferative neoplasms. In a phase 1/2 study in myelofibrosis patients, once-daily dosing of a 300-mg momelotinib capsule was selected for further development based on a favorable benefit:risk profile. A tablet formulation was recently developed for further clinical evaluation. In this study, the relative bioavailability of the tablet formulation versus the initial capsule formulation and the effect of food and omeprazole on the pharmacokinetics of a single-dose momelotinib tablet were evaluated in healthy subjects...
October 11, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/29022213/high-prevalence-of-heparin-induced-thrombocytopenia-with-thrombosis-among-patients-with-essential-thrombocytemia-carrying-v617f-mutation
#12
Roberto Castelli, Paolo Gallipoli, Riccardo Schiavon, Thomas Teatini, Giorgio Lambertenghi Deliliers, Luigi Bergamaschini
Arterial and venous complications are major causes of morbidity and mortality in myeloproliferative neoplasms (MPNs). MPNs patients, frequently receive heparin. Heparin-induced thrombocytopenia (HIT) is a rare but potentially life-threatening complication resulting in a severe acquired thrombophilic condition. We carried out a retrospective analysis to evaluate occurrence of new thrombotic events during heparin therapy in essential thrombocythemia (ET) patients. We studied 108 ET patients on heparin for treatment of previous thrombotic events or in thromboprophilaxis...
October 11, 2017: Journal of Thrombosis and Thrombolysis
https://www.readbyqxmd.com/read/29022201/increased-mean-platelet-volume-mpv-is-an-independent-predictor-of-inferior-survival-in-patients-with-primary-and-secondary-myelofibrosis
#13
Marko Lucijanic, Zdravko Mitrovic, David Cicic, Zeljko Prka, Vlatko Pejsa, Ana Livun, Tajana Stoos-Veic, Zeljko Romic, Marcela Zivkovic, Iva Lucijanic, Zrinka Fabris, Rajko Kusec
Neoplastic megakaryopoiesis is a dominant feature of Philadelphia-chromosome-negative myeloproliferative neoplasms (Ph- MPNs), and elevated mean-platelet-volume (MPV) is a common finding in these diseases. The clinical and prognostic significances of MPV in patients with primary (PMF) and secondary myelofibrosis (SMF) have not been reported. We retrospectively analyzed 87 patients with myelofibrosis (66 with PMF, 21 with SMF) treated at our institution. MPV was recorded in addition to other hematological and clinical parameters...
October 11, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/29019736/clinical-and-laboratory-assessment-of-a-patient-with-thrombocytosis
#14
Niamh Appleby, Daniel Angelov
Elevated platelet counts are frequently encountered in hospital medicine and arise from both physiological and pathological mechanisms. Thrombocytosis may be secondary, reflecting an inflammatory state, iron deficiency, recent surgery or point towards an underlying neoplasm. Thrombocytosis may be the presenting sign of solid tumours and haematological conditions. The discovery of the activating mutations affecting thrombopoiesis led to greater understanding of the pathobiology of essential thrombocythaemia and other myeloproliferative neoplasms...
October 2, 2017: British Journal of Hospital Medicine
https://www.readbyqxmd.com/read/28991281/trombosis-venosa-espl%C3%A3-cnica-como-manifestaci%C3%A3-n-inicial-de-mielofibrosis-primaria
#15
Gregorio Campos-Cabrera, Virginia Campos-Cabrera, Salvador Campos-Cabrera, José-Luis Campos-Villagómez, Alejandra Romero-González
other: Las neoplasias mieloproliferativas (NMP) son alteraciones crónicas de las células madre hematopoyéticas clonales caracterizadas por una mayor producción de granulocitos, glóbulos rojos o plaquetas. Una de las principales complicaciones de las NMP es la aparición de problemas trombóticos venosos y arteriales causados por un aumento en la agregación plaquetaria y la generación de trombina. Se evaluaron 11 casos de mielofibrosis primaria (MP), de los cuales dos debutaron con trombosis venosa esplácnica (TVE)...
2017: Revista de Investigación Clínica; Organo del Hospital de Enfermedades de la Nutrición
https://www.readbyqxmd.com/read/28990497/calr-jak2-and-mpl-mutation-status-in-argentinean-patients-with-bcr-abl1-negative-myeloproliferative-neoplasms
#16
Mara Jorgelina Ojeda, Irma Margarita Bragós, Karina Lucrecia Calvo, Gladis Marcela Williams, María Magdalena Carbonell, Arianna Flavia Pratti
OBJECTIVES: To establish the frequency of JAK2, MPL and CALR mutations in Argentinean patients with BCR-ABL1-negative  myeloproliferative neoplasms (MPN) and to compare their clinical and haematological features. METHODS: Mutations of JAK2V617F, JAK2 exon 12, MPL W515L/K and CALR were analysed in 439 Argentinean patients with BCR-ABL1-negative MPN, including 176 polycythemia vera (PV), 214 essential thrombocythemia (ET) and 49 primary myelofibrosis (PMF). RESULTS: In 94...
October 9, 2017: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/28988389/treatment-free-remission-a-new-therapeutic-goal-in-chronic-myelogenous-leukemia
#17
REVIEW
Ahmed Gamal Elsayed, Roma Srivastava, Muhammad Omer Jamil
PURPOSE OF REVIEW: Chronic myelogenous leukemia (CML) is a chronic myeloproliferative neoplasm characterized by the presence of Philadelphia chromosome [t(9:22)] leading to the presence of pathognomonic fusion gene product, BCR-ABL1. This leads to constitutive activation of ABL1 kinase. CML was a difficult-to-treat illness until the advent of small molecule tyrosine kinase inhibitor (TKI), imatinib which revolutionized therapy of CML. Since then, multiple second- and third-generation TKIs have been formulated which have proven effective and has led to marked improvement in survival...
October 7, 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28983777/therapy-for-chronic-myelomonocytic-leukemia-in-a-new-era
#18
REVIEW
Tamara K Moyo, Michael R Savona
Chronic myelomonocytic leukemia (CMML) is a myeloid malignancy which shares clinical and morphologic features of myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPNs) and is classified by the WHO as an MDS/MPN. The defining feature of CMML is clonal hematopoiesis that results in peripheral monocytosis. The benefit of early treatment is currently unclear, and treatment may be held until the disease exhibits accelerated blast counts or the patient becomes symptomatic. Optimal treatments for CMML are not well defined...
October 6, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28982745/nccn-guidelines-insights-myeloproliferative-neoplasms-version-2-2018
#19
Ruben A Mesa, Catriona Jamieson, Ravi Bhatia, Michael W Deininger, Christopher D Fletcher, Aaron T Gerds, Ivana Gojo, Jason Gotlib, Krishna Gundabolu, Gabriela Hobbs, Brandon McMahon, Sanjay R Mohan, Stephen Oh, Eric Padron, Nikolaos Papadantonakis, Philip Pancari, Nikolai Podoltsev, Raajit Rampal, Erik Ranheim, Vishnu Reddy, Lindsay A M Rein, Bart Scott, David S Snyder, Brady L Stein, Moshe Talpaz, Srdan Verstovsek, Martha Wadleigh, Eunice S Wang, Mary Anne Bergman, Kristina M Gregory, Hema Sundar
Myeloproliferative neoplasms (MPNs) are a group of heterogeneous disorders of the hematopoietic system that include myelofibrosis (MF), polycythemia vera (PV), and essential thrombocythemia (ET). PV and ET are characterized by significant thrombohemorrhagic complications and a high risk of transformation to MF and acute myeloid leukemia. The diagnosis and management of PV and ET has evolved since the identification of mutations implicated in their pathogenesis. These NCCN Guideline Insights discuss the recommendations outlined in the NCCN Guidelines for the risk stratification, treatment, and special considerations for the management of PV and ET...
October 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/28978863/myeloid-neoplasms-in-the-world-health-organization-2016-classification
#20
Norio Asou
In the 2016 revision of the World Health Organization (WHO) classification, the categories of myeloid neoplasms have not been revised significantly from the 2008 fourth edition. However, recent discovery of molecular abnormalities provides a new perspective regarding the diagnostic and prognostic markers. In myeloproliferative neoplasms, the identification of CALR gene mutation, in addition to the JAK2 and MPL mutations, has impacted the diagnostic criteria. In myelodysplastic syndromes and acute myeloid leukemia, in addition to alterations in the transcription factors and signal transduction pathways, discovery of gene mutations in the epigenetic regulators that are involved in DNA methylation, histone modification, cohesin complex, and RNA splicing, by comprehensive genetic analyses, has improved our understanding of the pathobiology of these diseases...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
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