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myeloproliferative chronic neoplasm

Vani Chandrashekar, Anil Tarigopula
Platelet distribution width (PDW) and mean platelet volume are markers of platelet activation and have prognostic value in coronary heart diseases, as well as in cancers of solid organs. In this study, we evaluated the possibility of using PDW to predict chronic myeloproliferative neoplasms by comparing platelet indices obtained by automated analyzers in chronic myeloproliferative neoplasms with those in control specimens. We found that PDW greater than 66.4% has specificity of 99% and likelihood ratio of 19...
October 17, 2018: Laboratory Medicine
Caroline J McNamara, Tony Panzarella, James A Kennedy, Andrea Arruda, Jaime O Claudio, Georgina Daher-Reyes, Jenny Ho, Nancy Siddiq, Rebecca Devlin, Hubert Tsui, Jie Su, Tracy Stockley, Mahadeo Sukhai, Nisha Kanwar, Steven Chan, Dawn Maze, Aaron Schimmer, Andre Schuh, Hassan Sibai, Auro Viswabandya, Karen Yee, Mark D Minden, Suzanne Kamel-Reid, Vikas Gupta
There is a paucity of data regarding the impact of mutations on outcomes in accelerated-phase (AP) and blast-phase (BP) myeloproliferative neoplasms (MPNs). Moreover, it is unknown whether mutational status affects survival, as seen in chronic-phase MPNs. Therefore, we performed a retrospective analysis of all patients treated at our institution with AP/BP MPNs (N = 122; AP = 14; BP = 108) to comprehensively describe the mutational profile and correlate with clinical outcomes. Targeted sequencing with a 54-gene panel was performed...
October 23, 2018: Blood Advances
Houssam Rebahi, Mourad Ait Sliman, Ahmed-Rhassane El Adib
Background: Chronic Myeloid Leukemia (CML) is a myeloproliferative neoplasm related to chromosomal reciprocal translocation t(9;22). Tyrosine kinase inhibitors (TKIs) such as imatinib have drastically revolutionized the course and the prognosis of this hematologic malignancy. As we know, the association pregnancy-CML is an infrequent situation. Also the use of TKI in pregnant women is unsafe with a lack of alternatives and effective therapeutic options. Thus its cessation during gestation puts those patients at high risk of developing blast crisis characterized by poor outcomes...
2018: Case Reports in Obstetrics and Gynecology
Johanna S Ungerstedt
Myeloid hematological malignancies are clonal bone marrow neoplasms, comprising of acute myeloid leukemia (AML), the myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), the myeloproliferative neoplasms (MPN) and systemic mastocytosis (SM). The field of epigenetic regulation of normal and malignant hematopoiesis is rapidly growing. In recent years, heterozygous somatic mutations in genes encoding epigenetic regulators have been found in all subtypes of myeloid malignancies, supporting the rationale for treatment with epigenetic modifiers...
October 9, 2018: International Journal of Molecular Sciences
Jacob Grinfeld, Jyoti Nangalia, E Joanna Baxter, David C Wedge, Nicos Angelopoulos, Robert Cantrill, Anna L Godfrey, Elli Papaemmanuil, Gunes Gundem, Cathy MacLean, Julia Cook, Laura O'Neil, Sarah O'Meara, Jon W Teague, Adam P Butler, Charlie E Massie, Nicholas Williams, Francesca L Nice, Christen L Andersen, Hans C Hasselbalch, Paola Guglielmelli, Mary F McMullin, Alessandro M Vannucchi, Claire N Harrison, Moritz Gerstung, Anthony R Green, Peter J Campbell
BACKGROUND: Myeloproliferative neoplasms, such as polycythemia vera, essential thrombocythemia, and myelofibrosis, are chronic hematologic cancers with varied progression rates. The genomic characterization of patients with myeloproliferative neoplasms offers the potential for personalized diagnosis, risk stratification, and treatment. METHODS: We sequenced coding exons from 69 myeloid cancer genes in patients with myeloproliferative neoplasms, comprehensively annotating driver mutations and copy-number changes...
October 11, 2018: New England Journal of Medicine
S E Shalihin, Z Harun, I F Osman
Essential thrombocythemia is one of the myeloproliferative neoplasms. Palpable purpura is a rare manifestation that may delay diagnosis and treatment. We report a case of essential thrombocythemia in a 50-year-old man, who presented with recurrent thigh pain for the past one year with nonspecific localized purpura. His full blood count revealed isolated thrombocytosis of 880,000/µL with an impression of myeloproliferative disorder from peripheral blood film. He was referred urgently to the hematology team, which proceeded with a venesection...
2018: Malaysian Family Physician
Mei Tan, Xi Luo, Qiong Su, Cheng-Shuang Huang, Yu-Hang Yang, Ying Rong, Ping Zhu, Yan Chen
OBJECTIVE: To detect the mutation and single nucleotide polymorphisms of STAT3 gene in the patients with myeloproliferative neoplasms (MPN), and to analyze the correlation between STAT3 gene and the subtypes of MPN. METHODS: A total of 147 patients with MPN were selected, including 28 patients with polycythaemia vera (PV), 46 patients with essential thrombocythemia (ET), 10 patients with primary myelofibrosis (PMF), and 63 patients with chronic myeloid leukemia (CML); and 88 healthy persons were used as normal control...
October 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
Amandeep Aujla, Katherine Linder, Chaitanya Iragavarapu, Michael Karass, Delong Liu
Recurrent gene mutations have been described with varying frequencies in myelodysplasia (MDS) /myeloproliferative neoplasm (MPN) overlap syndromes (MMOS). Recent work has placed significant focus on understanding the role of gene lesions involving the spliceosomal machinery in leukemogeneis. SRSF2 is a gene encoding critical spliceosomal proteins. SRSF2 mutations appear to play an important role in pathogenesis of MMOS, particularly in chronic myelomonocytic leukemia. Inhibition of splicing may be a new therapeutic approach...
2018: Biomarker Research
M Palova, L Slavik, A Hlusi, T Szotkowski, J Ulehlova, M Divoka, J Navratilova, T Papajik
BACKGROUND: Primary myelofibrosis (PMF) is a chronic clonal myeloid disorder. Together with essential thrombocythemia (ET) and polycythemia vera (PV), it belongs to a group of Philadelphia chromosome-negative myeloproliferative neoplasms. Thrombotic events are serious complications negatively influencing the quality and length of these patients' lives. The confirmed risk factors for venous thromboembolism are age over 60 years, a positive history of thromboembolism, presence of common cardiovascular risks, JAK2 V617F mutation and, according to some authors, leukocytosis...
September 1, 2018: Clinical Laboratory
Chiara Rossi, Roberta Zini, Sebastiano Rontauroli, Samantha Ruberti, Zelia Prudente, Greta Barbieri, Elisa Bianchi, Simona Salati, Elena Genovese, Niccolò Bartalucci, Paola Guglielmelli, Enrico Tagliafico, Vittorio Rosti, Giovanni Barosi, Alessandro M Vannucchi, Rossella Manfredini
Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by an excessive production of pro-inflammatory cytokines resulting in chronic inflammation and genomic instability. Beside the driver mutations in JAK2, MPL and CALR genes, the deregulation of miRNA expression may also contribute to the pathogenesis of PMF. To this end, we recently reported the upregulation of miR-382-5p in PMF CD34+ cells. In order to unveil the mechanistic details of the role of miR-382-5p in pathogenesis of PMF, we performed gene expression profiling of CD34+ cells overexpressing miR-382-5p...
September 27, 2018: Molecular Oncology
Amy Jencks, Katrin Kiavash, Steven Daveluy, Andrew D Thompson
Exaggerated insect bite reactions present as exuberant papular and vesiculobullous lesions in patients with hematologic malignant neoplasms. The most commonly reported hematological malignancy with exaggerated insect bite reactions is chronic lymphocytic leukemia. Other reported reactions have been seen in patients with mantle cell lymphoma. Clinical presentation may vary with many patients unaware of a previous insect bite. Therefore, the terms "exaggerated bite-like reaction" and "eosinophilic dermatosis of myeloproliferative disease" have been proposed...
September 24, 2018: American Journal of Dermatopathology
Mia Aaboe Jørgensen, Morten Orebo Holmström, Evelina Martinenaite, Caroline Hasselbalch Riley, Hans Carl Hasselbalch, Mads Hald Andersen
Compelling evidence supports the existence of a profound immune dysregulation in patients with chronic myeloproliferative neoplasms (MPN). Increased Arginase-1 expression has been described in MPN patients and in solid cancers. This increase contributes to an immunosuppressive tumor microenvironment in MPN patients because of L-arginine depletion by Arginase-1-expressing regulatory cells and cancer cells, which subsequently limits the activation of circulating effector cells. In the present study, we demonstrate that Arginase-1-derived peptides are recognized by T cells among peripheral mononuclear blood cells from MPN patients...
2018: Oncoimmunology
Katya Hristova Uzunova, Elena Pavlova Filipova, Toni Yonkov Vekov
Aim of Study: This review aims to highlight that bosutinib represents a valuable alternative for patients already treated unsuccessfully with one or more other tyrosine kinase inhibitors (TKIs). Chronic myelogenous leukemia (CML) is a myeloproliferative neoplasm associated with a specific genetic abnormality resulting in a fusion protein with an active tyrosine kinase region. Therefore, TKIs were developed as a suitable treatment option. Methods: Full-text articles, abstracts, and meta-analysis comparing the efficacy and safety of the five TKIs were included in the review...
July 2018: Journal of Cancer Research and Therapeutics
N A Mansor, N Yusof, Y L Tang, A Ithnin, R Z Azma, N R Tumian, S Shuib
INTRODUCTION: Essential thrombocythaemia (ET) is a chronic myeloproliferative neoplasm (MPN) characterised by persistent thombocytosis. It is an indolent disorder but transformation to myelofibrosis (MF), acute myeloid leukaemia (AML) or myelodyplastic syndrome (MDS) has been reported. CASE REPORT: We described a patient with ET whose disease evolved into MDS with fibrosis and complex karyotype after 15 years of stable disease. She was asymptomatic and was on hydroxyurea (HU) treatment until recently when she presented with worsening anaemia...
August 2018: Malaysian Journal of Pathology
Elvira Mora, Guillermo F Sanz
PURPOSE OF REVIEW: The present review focuses on the current management of patients with chronic myelomonocytic leukemia (CMML) and the most recent developments in the field. RECENT FINDINGS: CMML is a heterogeneous malignant myeloid disorder sharing features of myelodysplastic syndromes (MDS) and myeloproliferative neoplasms and characterized by peripheral blood monocytosis and increased risk of progression to acute leukemia. Its natural course is highly variable and use of CMML-specific prognostic scoring systems is strongly recommended for tailoring treatment...
November 2018: Current Opinion in Oncology
Salyka Sengsayadeth, Katie S Gatwood, Ariane Boumendil, Myriam Labopin, Jürgen Finke, Arnold Ganser, Matthias Stelljes, Gerhard Ehninger, Dietrich Beelen, Dietger Niederwieser, Didier Blaise, Peter Dreger, Ghulam Mufti, Patrice Chevallier, Audrey Mailhol, Maria H Gilleece, Norbert Gorin, Jordi Esteve, Fabio Ciceri, Frederic Baron, Christoph Schmid, Sebastian Giebel, Mohamad Mohty, Bipin N Savani, Arnon Nagler
Patients with secondary AML (sAML) with antecedent myelodysplastic syndrome (MDS) or myeloproliferative neoplasms (MPNs) tend to have high-risk disease based on the older age of patients, high-risk cytogenetics, and higher number of prior treatments. Allogeneic hematopoietic cell transplant (HCT) is the only potentially curative therapy available. Eight hundred and two adults with sAML and prior MDS/MPN who received a first HCT between 2000 and 2016 were included in the European Society for Blood and Marrow Transplant (EBMT) Acute Leukemia Working Party (ALWP) study...
August 28, 2018: Blood Advances
Rebecca F McClure, Mark D Ewalt, Jennifer Crow, Robyn L Temple-Smolkin, Mrudula Pullambhatla, Rachel Sargent, Annette S Kim
To address the clinical relevance of small DNA variants in chronic myeloid neoplasms (CMNs), an Association for Molecular Pathology Working Group comprehensively reviewed published literature, summarized key findings that support clinical utility, and defined critical gene inclusions for high-throughput sequencing testing panels. This review highlights the biological complexity of CMNs [including myelodysplastic syndromes, myeloproliferative neoplasms, entities with overlapping features (myelodysplastic syndromes/myeloproliferative neoplasms), and systemic mastocytosis], the genetic heterogeneity within diagnostic categories, and similarities between apparently disparate diagnostic entities...
August 20, 2018: Journal of Molecular Diagnostics: JMD
Zhen-Ling Li, Li Gao, Hui Zhang, Chun-Xia Zhang, Yan-Rong Chen, Fan-Zhou Huang, Ming Gong, Ya-Yue Gao, Yin Tang, Yi-Gai Ma
OBJECTIVE: To detect the JAK2, CALR and MPL gene mutations in patients with BCR/ABL1 negative chronic myeloproliferative diseases(BCR/ABL1-CMPD)and to evaluate their diagnostic value. METHODS: Two hundred and eight cases of BCR/ABL1-CMPD comprising of 146 cases of essential thrombocythemia(ET), 37 cases of polycythemia vera(PV)and 25 cases of primary myelofibrosis(PMF)from March 2012 to December 2015 were enrolled in the BCR/ABL1-CMPD, while 124 cases of secondary thrombocythemia and 73 cases of secondary polycythemia were enrolled in the control group...
August 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
Lauren C Schwartz, John Mascarenhas
Atypical chronic myeloid leukemia (aCML) is a BCR-ABL1 negative myelodysplastic (MDS)/myeloproliferative (MPN) neoplasm with poor overall survival. The current 2016 WHO classification of myeloid neoplasms allows clinicians to more accurately differentiate aCML from its similar MDS/MPN overlap and MPN counterparts. In addition, the advent of next-generation sequencing has expanded our understanding of the molecular pathogenesis of aCML and its therapeutic potential. Hematopoietic stem cell transplant (HSCT) remains the first consideration in the treatment algorithm for aCML, however, with the advances in mutational analysis, opportunities for targeted therapy have expanded...
July 29, 2018: Blood Reviews
Camilla de S Borges, Aline F Ferreira, Vitor H Almeida, Fausto G Gomes, Maria Gabriela Berzoti-Coelho, Maira da Costa Cacemiro, Natalia S Nunes, Lorena L Figueiredo-Pontes, Belinda P Simões, Fabíola A Castro, Robson Q Monteiro
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by the presence of the Philadelphia chromosome, which generates the oncogene BCR-ABL1. Protease-activated receptor 1 (PAR1) is involved in tumor progression and angiogenesis. We have previously reported that PAR1 expression is elevated in human leukemias that display a more aggressive clinical behavior, including the blast crisis of CML. In this study, we analyzed the crosstalk between the oncoprotein BCR-ABL and PAR1 in CML. Leukemic cell lines transfected with the BCR-ABL1 oncogene showed significantly higher expression levels of PAR1 compared with that of wild-type counterparts...
August 1, 2018: Experimental Hematology
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