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https://www.readbyqxmd.com/read/29327708/myeloproliferative-neoplasms-with-concurrent-bcr-abl1-translocation-and-jak2-v617f-mutation-a-multi-institutional-study-from-the-bone-marrow-pathology-group
#1
Craig R Soderquist, Mark D Ewalt, David R Czuchlewski, Julia T Geyer, Heesun J Rogers, Eric D Hsi, Sa A Wang, Carlos E Bueso-Ramos, Attilio Orazi, Daniel A Arber, Elizabeth O Hexner, Daria V Babushok, Adam Bagg
Myeloproliferative neoplasms arise from hematopoietic stem cells with somatically altered tyrosine kinase signaling. Classification of myeloproliferative neoplasms is based on hematologic, histopathologic and molecular characteristics including the presence of the BCR-ABL1 and JAK2 V617F. Although thought to be mutually exclusive, a number of cases with co-occurring BCR-ABL1 and JAK2 V617F have been identified. To characterize the clinicopathologic features of myeloproliferative neoplasms with concomitant BCR-ABL1 and JAK2 V617F, and define the frequency of co-occurrence, we conducted a retrospective multi-institutional study...
January 12, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29323541/development-of-a-targeted-next-generation-sequencing-assay-to-detect-diagnostically-relevant-mutations-of-jak2-calr-and-mpl-in-myeloproliferative-neoplasms
#2
Thomas Frawley, Cathal P O'Brien, Eibhlin Conneally, Elisabeth Vandenberghe, Melanie Percy, Stephen E Langabeer, Karl Haslam
BACKGROUND: The classical Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), consisting of polycythemia vera, essential thrombocythemia, and primary myelofibrosis, are a heterogeneous group of neoplasms that harbor driver mutations in the JAK2, CALR, and MPL genes. The detection of these mutations has been incorporated into the recent World Health Organization (WHO) diagnostic criteria for MPN. Given a pressing clinical need to screen for these mutations in a routine diagnostic setting, a targeted next-generation sequencing (NGS) assay for the detection of MPN-associated mutations located in JAK2 exon 14, JAK2 exon 12, CALR exon 9, and MPL exon 10 was developed to provide a single platform alternative to reflexive, stepwise diagnostic algorithms...
January 11, 2018: Genetic Testing and Molecular Biomarkers
https://www.readbyqxmd.com/read/29323084/fibroblast-growth-factor-receptor-1-associated-myeloproliferative-neoplasm-and-t-lymphoblastic-lymphoma
#3
Gayathri Gopan, T M Anoop, N P Prakash, Rakul Nambiar, R Krishnachandran
Myeloid and lymphoid hematological malignancies with eosinophilia and abnormalities of fibroblast growth factor receptor-1 (FGFR1) result from the formation of abnormal fusion genes that encode constitutively activated tyrosine kinases. The WHO classification (2008) of hematolymphoid neoplasms recognizes a category of myeloid and lymphoid neoplasms with eosinophilia and abnormalities of FGFR1. Here, we present the case of a 30-year-old-woman who was diagnosed with T-lymphoblastic lymphoma from lymph node biopsy and myeloproliferative neoplasm with eosinophilia from bone marrow studies...
October 2017: Indian Journal of Pathology & Microbiology
https://www.readbyqxmd.com/read/29321520/essential-thrombocythemia-treatment-algorithm-2018
#4
REVIEW
Ayalew Tefferi, Alessandro M Vannucchi, Tiziano Barbui
Current drug therapy for myeloproliferative neoplasms, including essential thrombocythemia (ET) and polycythemia vera (PV), is neither curative nor has it been shown to prolong survival. Fortunately, prognosis in ET and PV is relatively good, with median survivals in younger patients estimated at 33 and 24 years, respectively. Therefore, when it comes to treatment in ET or PV, less is more and one should avoid exposing patients to new drugs that have not been shown to be disease-modifying, and whose long-term consequences are suspect (e...
January 10, 2018: Blood Cancer Journal
https://www.readbyqxmd.com/read/29316431/bet-ing-on-dual-jak-bet-inhibition-as-a-therapeutic-strategy-for-myeloproliferative-neoplasms
#5
Qingfei Jiang, Catriona Jamieson
In this issue of Cancer Cell, Kleppe et al. describe a combination strategy designed to inhibit BET bromodomain and JAK/STAT signaling as a method for effectively inhibiting NF-κB and cytokine production in myeloproliferative neoplasms (MPNs). The results provide a strong rationale for clinical evaluation of dual BET/JAK inhibition in MPNs.
January 8, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29313725/prognostic-risk-model-for-patients-with-high-risk-polycythemia-vera-and-essential-thrombocythemia
#6
Abhishek A Mangaonkar, Katherine P Hoversten, Naseema Gangat
Polycythemia Vera (PV) and essential thrombocythemia (ET) are the most frequent Philadelphia chromosome-negative myeloproliferative neoplasms, the other entity being myelofibrosis. Management of patients with PV and ET is fraught with difficulties as they have an inherent tendency to cause thrombotic and hemorrhagic events. There are no curative treatment options therefore it is important that a risk-adapted treatment approach is applied. Areas covered: This review discusses existing literature about prognosis in PV and ET, and addresses critical aspects related to defining 'high-risk' disease...
January 9, 2018: Expert Review of Hematology
https://www.readbyqxmd.com/read/29311136/pharmacokinetics-and-disposition-of-momelotinib-revealed-a-disproportionate-human-metabolite-%C3%A2-resolution-for-clinical-development
#7
Jim Zheng, Yan Xin, Jingyu Zhang, Raju Subramanian, Bernard P Murray, J Andrew Whitney, Matthew R Warr, John Ling, Lisa Moorehead, Ellen Kwan, Jeffrey Hemenway, Bill J Smith, Jeffrey A Silverman
Momelotinib (MMB) is a small molecule inhibitor of Janus kinase (JAK)1/2 and of activin A receptor type 1 (ACVR1), in clinical development for the treatment of myeloproliferative neoplasms. The pharmacokinetics and disposition of [14C]MMB were characterized in a single-dose, human mass balance study. Metabolism and the pharmacologic activity of key metabolites were elucidated in multiple in vitro and in vivo experiments. MMB was rapidly absorbed following oral dosing with approximately 97% of the radioactivity recovered, primarily in feces with urine as a secondary route...
January 8, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29306106/quantitative-assessment-of-jak2-v617f-and-calr-mutations-in-philadelphia-negative-myeloproliferative-neoplasms
#8
Ambrus Gángó, Réka Mózes, Zsófia Boha, Béla Kajtár, Botond Timár, Péter Attila Király, Richárd Kiss, Viktória Fésüs, Noémi Nagy, Judit Demeter, Gábor Körösmezey, Zita Borbényi, Imelda Marton, Anita Szőke, Tamás Masszi, Péter Farkas, Judit Várkonyi, Márk Plander, Éva Pósfai, Miklós Egyed, Katalin Pál, Gáspár Radványi, Aryan Hamed, Judit Csomor, András Matolcsy, Donát Alpár, Csaba Bödör
BACKGROUND: Philadelphia negative myeloproliferative neoplasms (MPNs) are characterized by frequent mutations of driver genes including JAK2, CALR and MPL. While the influence of JAK2 V617F mutant allele burden on the clinical phenotype of MPN patients is well-described, the impact of CALR mutant allele burden on clinical features needs further investigation. PATIENTS AND METHODS: Quantitative assessment of JAK2 and CALR mutations was performed on diagnostic DNA samples from 425 essential thrombocythemia (ET) and 227 primary myelofibrosis patients using real-time quantitative PCR and fragment length analysis...
January 2, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29305495/myeloproliferative-neoplasms-may-be-sensitive-to-dual-bet-jak-inhibition
#9
(no author information available yet)
In myeloproliferative neoplasms (MPN) chromatin changes promote NF-κB signaling to drive inflammation.
January 5, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29299961/erythromelalgia
#10
Peter Franz Klein-Weigel, Theresa Sophie Volz, Jutta Gisela Richter
Erythromelalgia is a rare syndrome characterized by the intermittent or, less commonly, by the permanent occurrence of extremely painful hyperperfused skin areas mainly located in the distal extremities. Primary erythromelalgia is nowadays considered to be a genetically determined neuropathic disorder affecting SCN9A, SCN10A, and SCN11A coding for NaV1.7, NaV1.8, and NaV1.9 neuronal sodium channels. Secondary forms might be associated with myeloproliferative disorders, connective tissue disease, cancer, infections, and poisoning...
January 4, 2018: VASA. Zeitschrift Für Gefässkrankheiten
https://www.readbyqxmd.com/read/29296779/overexpression-of-runx1-short-isoform-has-an-important-role-in-the-development-of-myelodysplastic-myeloproliferative-neoplasms
#11
Hiroko Sakurai, Yuka Harada, Yosuke Ogata, Yuki Kagiyama, Naoki Shingai, Noriko Doki, Kazuteru Ohashi, Toshio Kitamura, Norio Komatsu, Hironori Harada
RUNX1a, but not RUNX1b, is overexpressed in CD34+ cells from patients with myelodysplastic/myeloproliferative neoplasms.SRSF2P95H mutation induces RUNX1a overexpression and a monocytic phenotype in TF-1 cells.
August 8, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296774/treated-secondary-acute-myeloid-leukemia-a-distinct-high-risk-subset-of-aml-with-adverse-prognosis
#12
Prajwal Boddu, Hagop M Kantarjian, Guillermo Garcia-Manero, Farhad Ravandi, Srdan Verstovsek, Elias Jabbour, Gautam Borthakur, Marina Konopleva, Kapil N Bhalla, Naval Daver, Courtney D DiNardo, Christopher B Benton, Koichi Takahashi, Zeev Estrov, Sherry R Pierce, Michael Andreeff, Jorge E Cortes, Tapan M Kadia
Secondary acute myeloid leukemia (s-AML) includes therapy-related AML and AML evolving from antecedent hematological disorder (AHD). s-AML arising after treating AHD likely represents a prognostically distinct, high-risk disease category. In this study, treated s-AML (ts-AML) was defined by: (1) prior diagnosis of myelodysplasia, myeloproliferative neoplasm, or aplastic anemia and (2) at least 1 therapy for that diagnosis. ts-AML was categorized by age (< or ≥60 years), and each cohort assessed for response rates and overall survival (OS) on various treatment regimens...
July 25, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296743/hmga2-collaborates-with-jak2v617f-in-the-development-of-myeloproliferative-neoplasms
#13
Koki Ueda, Kazuhiko Ikeda, Takayuki Ikezoe, Kayo Harada-Shirado, Kazuei Ogawa, Yuko Hashimoto, Takahiro Sano, Hiroshi Ohkawara, Satoshi Kimura, Akiko Shichishima-Nakamura, Yuichi Nakamura, Yayoi Shikama, Tsutomu Mori, Philip J Mason, Monica Bessler, Soji Morishita, Norio Komatsu, Kotaro Shide, Kazuya Shimoda, Shuhei Koide, Kazumasa Aoyama, Motohiko Oshima, Atsushi Iwama, Yasuchika Takeishi
High-mobility group AT-hook 2 (HMGA2) is crucial for the self-renewal of fetal hematopoietic stem cells (HSCs) but is downregulated in adult HSCs via repression by MIRlet-7 and the polycomb-recessive complex 2 (PRC2) including EZH2. The HMGA2 messenger RNA (mRNA) level is often elevated in patients with myelofibrosis that exhibits an advanced myeloproliferative neoplasm (MPN) subtype, and deletion of Ezh2 promotes the progression of severe myelofibrosis in JAK2V617F mice with upregulation of several oncogenes such as Hmga2...
June 27, 2017: Blood Advances
https://www.readbyqxmd.com/read/29295644/coincidence-of-5q-deletion-and-the-jak2v617f-mutation-report-of-two-patients-with-overlapping-myelodysplastic-and-myeloproliferative-features-and-review-of-the-literature
#14
Susanne Bürki, Evgenii Shumilov, Nicolas Bonadies, Johanna Flach, Myriam Legros, Yara Banz, Elisabeth Oppliger-Leibundgut, Martin Fiedler, Anne Angelillo-Scherrer, Alicia Rovo, Ulrike Bacher
No abstract text is available yet for this article.
January 3, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29288910/3q26-evi1-rearrangement-in-myelodysplastic-myeloproliferative-neoplasms-an-early-event-associated-with-a-poor-prognosis
#15
Zhihong Hu, Shimin Hu, Changsheng Ji, Zhenya Tang, Beenu Thakral, Sanam Loghavi, L Jeffrey Medeiros, Wei Wang
3q26.2/EVI1 rearrangements resulting in EVI1 overexpression play an important role in leukemogenesis and are associated with treatment resistance and a poorer prognosis in patients with acute myeloid leukemia, myelodysplastic syndrome, chronic myeloid leukemia and BCR-ABL negative myeloproliferative neoplasms. In this study, we aim to explore the clinicopathological features of myelodysplastic/myeloproliferative (MDS/MPN) neoplasms with 3q26.2/EVI1 rearrangements and determine the potential impact of these cytogenetic abnormalities on treatment response and survival...
December 23, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29288169/defining-the-requirements-for-the-pathogenic-interaction-between-mutant-calreticulin-and-mpl-in-mpn
#16
Shannon Elf, Nouran S Abdelfattah, April J Baral, Danielle Beeson, Jeanne F Rivera, Amy Ko, Natalie Florescu, Gabriel Birrane, Edwin Chen, Ann Mullally
Mutations in calreticulin (CALR) are phenotypic drivers in the pathogenesis of myeloproliferative neoplasms (MPN). Mechanistic studies have demonstrated that mutant CALR binds to the thrombopoietin receptor MPL, and that the positive electrostatic charge of the mutant CALR C-terminus is required for mutant CALR-mediated activation of JAK-STAT signaling. Here we demonstrate that although binding between mutant CALR and MPL is required for mutant CALR to transform hematopoietic cells, binding alone is insufficient for cytokine independent growth...
December 29, 2017: Blood
https://www.readbyqxmd.com/read/29285598/diagnosis-of-budd-chiari-syndrome
#17
Morgane Van Wettere, Onorina Bruno, Pierre-Emmanuel Rautou, Valérie Vilgrain, Maxime Ronot
Budd-Chiari syndrome (BCS) is defined by clinical and laboratory signs associated with partial or complete impairment of hepatic venous drainage in the absence of right heart failure or constrictive pericarditis. Primary BCS is the most frequent type and is a complication of hypercoagulable states, in particular myeloproliferative neoplasms. Secondary BCS involves tumor invasion or extrinsic compression. Most patients present with chronic BCS including a non-cirrhotic, dysmorphic, chronic liver disease with various degrees of fibrosis deposition...
December 28, 2017: Abdominal Radiology
https://www.readbyqxmd.com/read/29282357/risk-factors-for-arterial-versus-venous-thrombosis-in-polycythemia-vera-a-single-center-experience-in-587-patients
#18
S Cerquozzi, D Barraco, T Lasho, C Finke, C A Hanson, R P Ketterling, A Pardanani, N Gangat, A Tefferi
In a recent International Working Group on Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) study, prior arterial events and hypertension were predictors of subsequent arterial thrombosis whereas prior venous events and age ≥65 years predicted venous thrombosis in polycythemia vera (PV). In the current study, we sought to validate the above findings and identify additional predictors of arterial versus venous thrombosis. At a median follow up of 109 months, thrombosis after diagnosis occurred in 128 (22%) patients; 82 (14%) arterial and 57 (10%) venous events...
December 27, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/29277359/soho-state-of-the-art-update-and-next-questions-mpn
#19
REVIEW
Prithviraj Bose, Jason Gotlib, Claire N Harrison, Srdan Verstovsek
The discovery of the activating Janus kinase (JAK)2V617F mutation in 2005 in most patients with the classic Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) spurred intense interest in research into these disorders, culminating in the identification of activating mutations in MPL in 2006 and indels in the gene encoding calreticulin (CALR) in 2013, thus providing additional mechanistic explanations for the universal activation of JAK-signal transducer and activator of transcription (JAK-STAT) observed in these conditions, and the success of the JAK1/2 inhibitor ruxolitinib, which first received regulatory approval in 2011...
January 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29273914/myeloid-neoplasms-with-t-12-22-p13-q12-mn1-evt6-a-systematic-review-of-12-cases
#20
Haigang Shao, Jiannong Cen, Suning Chen, Huiying Qiu, Jinlan Pan
t(12;22)(p13;q12) is a rare but recurrent chromosomal abnormality involving the ETS transcription factor ETV6 and meningioma 1 (MN1) genes. In this study, we analyzed the clinical, cytogenetic, and molecular features of five new patients with the t(12;22)/MN1-EVT6 who presented with acute myeloid leukemia or chronic myelomonocytic leukemia. We subsequently reviewed the literature and identified seven additional cases reported with t(12;22)/MN1-EVT6. Our data suggest that neoplasms carrying the t(12;22)/MN1-ETV6, although rare, can commonly present as myeloid neoplasms at the initial diagnosis, including acute myeloid leukemia (n = 8), myelodysplastic syndrome (n = 2), and myelodysplastic/myeloproliferative neoplasms (n = 2)...
December 22, 2017: Annals of Hematology
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