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https://www.readbyqxmd.com/read/29164670/driver-mutations-and-prognosis-in-primary-myelofibrosis-mayo-careggi-mpn-alliance-study-of-1-095-patients
#1
Ayalew Tefferi, Maura Nicolosi, Mythri Mudireddy, Natasha Szuber, Christy M Finke, Terra L Lasho, Curtis A Hanson, Rhett P Ketterling, Animesh Pardanani, Naseema Gangat, Carmela Mannarelli, Tiziana Fanelli, Paola Guglielmelli, Alessandro M Vannucchi
The 2013 discovery of calreticulin (CALR) mutations in myeloproliferative neoplasms was attended by their association with longer survival in primary myelofibrosis (PMF). Subsequent studies have suggested prognostic distinction between type 1/like and type 2/like CALR mutations and detrimental effect from triple-negative mutational status. Among 709 Mayo Clinic patients with PMF, 467 (66%) harbored JAK2, 112 (16%) CALR type 1/like, 24 (3.4%) CALR type 2/like, 38 (5.4%) MPL mutations and 68 (10%) were triple-negative...
November 22, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/29164292/incidence-and-impact-of-atrial-arrhythmias-on-thrombotic-events-in-mpns
#2
Kristell Mahé, Aurélien Delluc, Aurélie Chauveau, Philippe Castellant, Dominique Mottier, Florence Dalbies, Christian Berthou, Gaëlle Guillerm, Eric Lippert, Jean-Christophe Ianotto
Atrial arrhythmias (AA) induce a high rate of thromboses and require vitamin K antagonists (VKA) or direct anticoagulants (DOAC) prescriptions. Essential thrombocythemia (ET) and polycythemia vera (PV) are also pro-thrombotic diseases. The prevention of thromboses is based on the association of cytoreductive drug and low-dose aspirin (LDA). We studied the incidence and complications of AA among patients with ET or PV. We identified 96/713 patients (13.5%) carrying AA. These patients were older (median 72.1 vs...
November 21, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/29162373/stabilisation-and-dewatering-of-primary-sludge-using-ferrate-vi-pre-treatment-followed-by-freeze-thaw-in-simulated-drainage-beds
#3
James Diak, Banu Örmeci
This study evaluated the ability of potassium ferrate(VI) and freeze-thaw to stabilise and dewater primary sludge. Potassium ferrate(VI) additions of 0.5 and 5.0 g/L were used as a pre-treatment prior to freeze-thaw. Samples were frozen at -10, -20 and -30 °C, and were kept frozen for 1, 8 and 15 days. The samples were subsequently thawed at room temperature in a setup which allowed meltwater to be separated from the sludge cake via gravity drainage. The meltwater was characterised in terms of fecal coliform, soluble chemical oxygen demand (COD), soluble proteins, soluble carbohydrates, pH and turbidity...
November 18, 2017: Journal of Environmental Management
https://www.readbyqxmd.com/read/29153976/image-based-ex-vivo-drug-screening-for-patients-with-aggressive-haematological-malignancies-interim-results-from-a-single-arm-open-label-pilot-study
#4
Berend Snijder, Gregory I Vladimer, Nikolaus Krall, Katsuhiro Miura, Ann-Sofie Schmolke, Christoph Kornauth, Oscar Lopez de la Fuente, Hye-Soo Choi, Emiel van der Kouwe, Sinan Gültekin, Lukas Kazianka, Johannes W Bigenzahn, Gregor Hoermann, Nicole Prutsch, Olaf Merkel, Anna Ringler, Monika Sabler, Georg Jeryczynski, Marius E Mayerhoefer, Ingrid Simonitsch-Klupp, Katharina Ocko, Franz Felberbauer, Leonhard Müllauer, Gerald W Prager, Belgin Korkmaz, Lukas Kenner, Wolfgang R Sperr, Robert Kralovics, Heinz Gisslinger, Peter Valent, Stefan Kubicek, Ulrich Jäger, Philipp B Staber, Giulio Superti-Furga
BACKGROUND: Patients with refractory or relapsed haematological malignancies have few treatment options and short survival times. Identification of effective therapies with genomic-based precision medicine is hampered by intratumour heterogeneity and incomplete understanding of the contribution of various mutations within specific cancer phenotypes. Ex-vivo drug-response profiling in patient biopsies might aid effective treatment identification; however, proof of its clinical utility is limited...
November 15, 2017: Lancet Haematology
https://www.readbyqxmd.com/read/29153093/next-generation-sequencing-and-molecular-cytogenetic-characterization-of-etv6-lyn-fusion-due-to-chromosomes-1-8-and-12-rearrangement-in-acute-myeloid-leukemia
#5
Edmond S K Ma, Thomas S K Wan, Chun Hang Au, Dona N Ho, Shing Yan Ma, Margaret H L Ng, Tsun Leung Chan
In a newly diagnosed patient with acute myeloid leukemia (AML) and complex cytogenetics and negative for gene mutations associated with myeloid neoplasms, RNA sequencing by next-generation sequencing (NGS) through a large cancer-related gene panel showed ETV6-LYN leukemic fusion transcript. Breakpoint analysis of the NGS reads showed fusion of exon 5 of the ETV6 gene to exon 8 of the LYN gene. Metaphase fluorescence in situ hybridization (FISH) inferred a four-break rearrangement of three chromosomes, namely 1, 8 and 12...
December 2017: Cancer Genetics
https://www.readbyqxmd.com/read/29150911/jak2-v617f-mutation-can-be-reliably-detected-in-serum-using-droplet-digital-pcr
#6
C F Nystrand, W Ghanima, A Waage, C M Jonassen
INTRODUCTION: Detection of the JAK2 V617F mutation is a key step in the diagnosis of myeloproliferative neoplasms (MPN). Sensitive real-time quantitative PCR (qPCR) detection on peripheral blood (PB) is the most widely used method. The main objective of this study was to determine whether serum, the most common material available in archival biobanks, is a good liquid biopsy for detecting and quantifying the JAK2 V617F mutation using droplet digital PCR (ddPCR). METHODS: Paired PB and serum samples from 66 patients with MPN were used...
November 17, 2017: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/29148089/impact-of-gene-mutations-on-treatment-response-and-prognosis-of-acute-myeloid-leukemia-secondary-to-myeloproliferative-neoplasms
#7
G Venton, F Courtier, A Charbonnier, E D'Incan, C Saillard, B Mohty, M J Mozziconacci, D Birnbaum, A Murati, N Vey, J Rey
Acute myeloid leukemias secondary (sAML) to myeloproliferative neoplasms (MPN) have variable clinical courses and outcomes, but remain almost always fatal. Large cohorts of sAML to MPN are difficult to obtain and there is very little scientific literature or prospective trials for determining robust prognostic markers and efficient treatments. We analyzed event-free survival (EFS) and overall survival (OS) of 73 patients with MPN who progressed to sAML, based on their epidemiological characteristics, the preexisting MPN, the different treatments received, the different prognostic groups and the responses achieved according to the ELN, and their mutational status determined by next-generation DNA sequencing (NGS)...
November 17, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/29145678/-thrombocytosis-and-thrombocytopenia-background-and-clinical-relevance
#8
Kai Wille, Parvis Sadjadian, Martin Griesshammer
Due to the central role of platelets in hemostasis, the clinical relevance of quantitative changes in platelet counts (< 150 G/l or > 450 G/l) may be significant. Thrombopoesis (= production of platelets) occurs in the bone marrow, and the hormone thrombopoetin takes control on its regulation.In thrombocytosis, primary causes have to be distinguished from the far more common reactive (= secondary) reasons. The most important form of primary thrombocytosis occurs in myeloproliferative neoplasms especially in essential thrombocythemia (ET)...
November 2017: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/29143068/patient-characteristics-and-outcomes-in-adolescents-and-young-adults-with-classical-philadelphia-chromosome-negative-myeloproliferative-neoplasms
#9
Prajwal Boddu, Lucia Masarova, Srdan Verstovsek, Paolo Strati, Hagop Kantarjian, Jorge Cortes, Zeev Estrov, Sherry Pierce, Naveen Pemmaraju
Little is known about the outcomes of Philadelphia-negative myeloproliferative neoplasms (MPNs) in adolescents and young adults (AYA). We reviewed all patients with essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF) treated at our institution from 1988 to 2016 who were aged 16 to 39 years (AYA) and described their outcomes in comparison to older MPN population. Of 2206 patients, 185 (8.3%) were identified as AYA: 105 (57%) ET, 43 (23%) PV, and 37 (20%) MF. The median age was 33 years [range, 16-39], and median follow-up time 3 years [range, 0...
November 15, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/29134817/the-bcr-abl1-negative-myeloproliferative-neoplasms-a-review-of-jak-inhibitors-in-the-therapeutic-armamentarium
#10
Martin Griesshammer, Parvis Sadjadian
The classical BCR-ABL1-negative myeloproliferative neoplasms (MPN) include primary myelofibrosis (PMF), polycythaemia vera (PV) and essential thrombocythaemia (ET). They are characterized by stem cell-derived clonal proliferation, harbour Janus kinase 2 (JAK2), or calreticulin (CALR), or myeloproliferative leukaemia virus oncogene (MPL) driver mutations and exert an over activated JAK-signal transducer and activator of transcription (STAT) pathway. Therefore JAK inhibiting strategies have been successfully investigated in MPN clinical trials...
November 14, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/29134664/a-phase-ii-trial-of-ruxolitinib-in-combination-with-azacytidine-in-myelodysplastic-syndrome-myeloproliferative-neoplasms
#11
Rita Assi, Hagop M Kantarjian, Guillermo Garcia-Manero, Jorge E Cortes, Naveen Pemmaraju, Xuemei Wang, Graciela Nogueras-Gonzalez, Elias Jabbour, Prithviraj Bose, Tapan Kadia, Courtney D Dinardo, Keyur Patel, Carlos Bueso-Ramos, Lingsha Zhou, Sherry Pierce, Romany Gergis, Carla Tuttle, Gautam Borthakur, Zeev Estrov, Rajyalakshmi Luthra, Juliana Hidalgo-Lopez, Srdan Verstovsek, Naval Daver
Ruxolitinib and azacytidine target distinct disease manifestations of myelodysplastic syndrome/myeloproliferative neoplasms (MDS/MPNs). Patients with MDS/MPNs initially received ruxolitinib BID (doses based on platelets count), continuously in 28-day cycles for the first 3 cycles. Azacytidine 25 mg/m(2) (Day 1-5) intravenously or subcutaneously was recommended to be added to each cycle starting cycle 4 and could be increased to 75 mg/m(2) (Days 1-5) for disease control. Azacytidine could be started earlier than cycle 4 and/or at higher dose in patients with rapidly proliferative disease or with elevated blasts...
November 14, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/29128551/transplant-decisions-in-patients-with-myelofibrosis-should-mutations-be-the-judge
#12
REVIEW
Rachel B Salit, H Joachim Deeg
The prognosis of myeloproliferative neoplasms (MPN), including primary myelofibrosis (PMF), polycythemia vera (PV; post-PV MF) and essential thrombocythemia (ET; post-EMF) varies considerably, between these disorders as well as within each diagnosis. Molecular studies have identified "driver mutations", in JAK2, MPL1 and CALR, and additional somatic DNA mutations, including ASXL1, EZH2, IDH1/2 and SRSF2, that affect prognosis differentially. Patients with mutations in CALR (type1) have a better outlook than patients with mutations in JAK2 or MPL, while patients without any of the driver mutations (triple negative) have the shortest life expectancy...
November 8, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29124948/tasigna-nilotinib-in-chronic-myeloid-leukemia%C3%A2-treatment-free-remission-after-nearly-2%C3%A2-years-an-interview-with-adam-mead
#13
Adam Mead
Dr Mead earned his medical degree from the University of Oxford and trained in hematology at St Bartholomew's Hospital and University College London. In 2007, he earned his PhD at UCL, which focused on the analysis of FLT3 mutations in acute myeloid leukemia. He is now Associate Professor of Hematology and MRC Senior Clinical Fellow at the WIMM, University of Oxford. His research group focuses on myeloid diseases and normal blood stem-cell biology. Dr Mead is the lead clinician for myeloproliferative neoplasms (MPN) and chronic myeloid leukemia in the Thames Valley Strategic Clinical Network and is the chief investigator for several chronic myeloid leukemia and MPN clinical trials...
November 10, 2017: Future Oncology
https://www.readbyqxmd.com/read/29121538/therapeutic-options-for-leukemic-transformation-in-patients-with-myeloproliferative-neoplasms
#14
REVIEW
Maliha Khan, Rabbia Siddiqi, Naseema Gangat
Approximately 5-10% of patients with Philadelphia chromosome negative myeloproliferative neoplasms (MPN) comprising of essential thrombocythemia, polycythemia vera and primary myelofibrosis) experience transformation to acute myeloid leukemia (AML, ≥20% blasts). Treatment options for post-MPN AML patients are limited, as conventional approaches like standard chemotherapy, fail to offer long-term benefit. Median survival for secondary AML is ∼2.4 months. Post-MPN AML therefore represents an area of urgent clinical need...
October 27, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29119847/myeloid-lymphoid-neoplasms-with-fgfr1-rearrangement
#15
Paolo Strati, Guilin Tang, Dzifa Y Duose, Saradhi Mallampati, Rajyalakshmi Luthra, Keyur P Patel, Mohammad Hussaini, Abu-Sayeef Mirza, Rami S Komrokji, Stephen Oh, John Mascarenhas, Vesna Najfeld, Vivek Subbiah, Hagop Kantarjian, Guillermo Garcia-Manero, Srdan Verstovsek, Naval Daver
Myeloid/lymphoid neoplasms with FGFR1 rearrangement are a rare entity. We present a multicenter experience of 17 patients with FISH-confirmed FGFR1 rearrangement. The clinical presentation at diagnosis included myeloproliferative neoplasm (MPN) in 4 (24%) patients, acute leukemia (AL) in 7 (41%), and concomitant MPN with AL in 6 (35%). The two most frequently observed cytogenetic abnormalities were t(8;13)(p11.2;q12)(partner gene ZMYM2) and t(8;22)(p11.2; q11.2)(BCR). Seventy-eight percent of tested patients had a RUNX1 mutation, of whom all had AL...
November 9, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29117429/old-meets-new-most-probable-number-validation-of-metagenomic-and-metatranscriptomic-datasets-in-soil
#16
Tim H Mauchline, Rifat Hayat, Ian M Clark, Penny R Hirsch
Metagenomics and metatranscriptomics provide insights into biological processes in complex substrates such as soil, but linking the presence and expression of genes with functions can be difficult. Here we obtain traditional most probable number estimates (MPN) of Rhizobium abundance in soil as a form of sample validation. Our work shows that in the Highfield experiment at Rothamsted, which has three contrasting conditions (> 50 years continual bare fallow, wheat and grassland), MPN based on host plant nodulation assays corroborate metagenomic and metatranscriptomic estimates for R...
November 8, 2017: Letters in Applied Microbiology
https://www.readbyqxmd.com/read/29107667/fgfr1-translocation-with-concurrent-myeloproliferative-neoplasm-systemic-mastocytosis-and-lymphoblastic-lymphoma-a-case-report
#17
Koping Chang, Jia-Hau Liu, Shan-Chi Yu, Chung-Wu Lin
FGFR1 translocation may cause myeloid or lymphoid neoplasm but rarely systemic mastocytosis (SM). Conversely, SM is associated with myeloproliferative neoplasm (MPN), but rarely lymphoblastic lymphoma (LBL) or FGFR1 translocation. We report the first case of FGFR1 translocation in a patient with concurrent LBL, MPN, and SM. A 21-year-old male patient presented with diffuse lymphadenopathies and leukocytosis. TdT(+)/cytoCD3(+)/CD79a(weakly+) LBL was identified in the lymph node. Bone marrow had MPN, SM, and TdT(+)/CD79a(+)/cytoCD3(weakly+) LBL...
October 28, 2017: Human Pathology
https://www.readbyqxmd.com/read/29105027/rare-cancers-and-social-media-analysis-of-twitter-metrics-in-the-first-2%C3%A2-years-of-a-rare-disease-community-for-myeloproliferative-neoplasms-on-social-media-mpnsm
#18
REVIEW
Naveen Pemmaraju, Audun Utengen, Vikas Gupta, Jean-Jacques Kiladjian, Ruben Mesa, Michael A Thompson
PURPOSE OF REVIEW: The use of social media has now become a standard 13 means of communication for many individuals worldwide. 14 The use of one specific form of social media, Twitter, has 15 increased among healthcare providers, both as a means of 16 information gathering and as a conduit for original content 17 creation. Recently, major efforts by users have been put for- 18 ward to help streamline the unprecedented amount of infor- 19 mation that can be found on Twitter. These efforts have led to 20 the creation of diseasespecific hashtag (#) medical communi- 21 ties and have greatly enhanced the ability to understand and 22 better categorize the available data on Twitter...
November 6, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/29104287/risk-of-developing-chronic-myeloid-neoplasms-in-well-differentiated-thyroid-cancer-patients-treated-with-radioactive-iodine
#19
R J Molenaar, C Pleyer, T Radivoyevitch, S Sidana, A Godley, A S Advani, A T Gerds, H E Carraway, M Kalaycio, A Nazha, D Adelstein, C Nasr, D Angelini, J P Maciejewski, N Majhail, M A Sekeres, S Mukherjee
Exposure to ionizing radiation increases the risk of myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN), but such risks are not known in well-differentiated thyroid cancer (WDTC) patients treated with radioactive iodine (RAI). A total of 148 215 WDTC patients were identified from Surveillance Epidemiology and End Results (SEER) registries between 1973 and 2014, of whom 54% underwent definitive thyroidectomy and 46% received adjuvant RAI. With a median follow-up of 6.6 years, 77 and 66 WDTC patients developed MDS and MPN, respectively...
November 6, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29100304/germline-variations-at-jak2-tert-hbs1l-myb-and-mecom-and-the-risk-of-myeloproliferative-neoplasms-in-taiwanese-population
#20
Yi-Hao Chiang, Yu-Cheng Chang, Huan-Chau Lin, Ling Huang, Chun-Chia Cheng, Wei-Ting Wang, Hung-I Cheng, Nai-Wen Su, Caleb Gon-Shen Chen, Johnson Lin, Yi-Fang Chang, Ming-Chih Chang, Ruey-Kuen Hsieh, Wen-Chien Chou, Ken-Hong Lim, Yuan-Yeh Kuo
Germline variations at JAK2, TERT, HBS1L-MYB and MECOM have been found to associate with myeloproliferative neoplasms (MPNs) in European populations. Whether these germline variations are associated with MPNs in Taiwanese population is obscure. Here we aimed to evaluate the association of five germline variations (JAK2 46/1 haplotype tagged by rs12343867, JAK2 intron 8 rs12339666, TERT rs2736100, HBS1L-MYB rs9376092 and MECOM rs2201862) and the risk of MPNs in Taiwanese population. A total of 178 MPN patients (109 essential thrombocythemia, 54 polycythemia vera and 15 primary myelofibrosis) were enrolled into this study...
September 29, 2017: Oncotarget
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