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myeloproliferative neoplasms

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https://www.readbyqxmd.com/read/28801515/lenalidomide-associated-arterial-thrombosis-in-a-patient-with-jak2-positive-atypical-myeloproliferative-neoplasm
#1
Tanesh Kumar Ayyalu, Meltiady Issa
No abstract text is available yet for this article.
August 11, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28798246/extramedullary-haematopoiesis-presenting-with-cardiac-tamponade-in-a-patient-with-polycythaemia-vera
#2
Faysal Haroun, Viktoria Elkis, Anne Chen, Elsie Lee
A 71-year-old man with a history of polycythaemia vera, diagnosed 4 years ago, presented to the emergency room with shortness of breath. A bedside echocardiogram revealed a large pericardial effusion with features concerning for pericardial tamponade. A left anterior thoracotomy and a pericardial window were emergently performed in the operating room and relieved the patient's symptoms. Histology evaluation of the pericardial fragments and pericardial fluid revealed the presence of trilineage haematopoietic elements without any increase in the blasts...
August 10, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28797996/detection-mutations-of-jak2-exon-12-in-patients-with-jak2-v617f-negative-myeloproliferative-disorders
#3
S Z Makani, N Parsamanesh, S Mirzaahmadi, M Hashemi, F Shaveisi-Zadeh, N Mansouri, M Ghazi, A Movafagh
BACKGROUND: Mutations in exon 12 of JAK2 gene are detected as clonal markers in hematopoietic lineages in myeloproliferative disorders (MPNs). Our aim was, to study the relation between N542-E543del mutation of JAK2 gene and myeloproliferative neoplasms in V617Fnegative patients. PATIENTS AND METHODS: DNA specimen from 34 patients and 44 healthy controls were genotyped using ARMs- PCR method. We analyzed exon 12 JAK2 aberration in 34 myeloproliferative cases to be readily detected by both ARMS-PCR and DNA analysis regardless of whether peripheral blood or bone marrow cells was manipulated as the origin of RNA...
May 2017: Gulf Journal of Oncology
https://www.readbyqxmd.com/read/28796790/mesenchymal-stromal-cells-msc-from-jak2-myeloproliferative-neoplasms-differ-from-normal-msc-and-contribute-to-the-maintenance-of-neoplastic-hematopoiesis
#4
Teresa L Ramos, Luis Ignacio Sánchez-Abarca, Beatriz Rosón-Burgo, Alba Redondo, Ana Rico, Silvia Preciado, Rebeca Ortega, Concepción Rodríguez, Sandra Muntión, Ángel Hernández-Hernández, Javier De Las Rivas, Marcos González, José Ramón González Porras, Consuelo Del Cañizo, Fermín Sánchez-Guijo
There is evidence of continuous bidirectional cross-talk between malignant cells and bone marrow-derived mesenchymal stromal cells (BM-MSC), which favors the emergence and progression of myeloproliferative neoplastic (MPN) diseases. In the current work we have compared the function and gene expression profile of BM-MSC from healthy donors (HD-MSC) and patients with MPN (JAK2V617F), showing no differences in the morphology, proliferation and differentiation capacity between both groups. However, BM-MSC from MPN expressed higher mean fluorescence intensity (MIF) of CD73, CD44 and CD90, whereas CD105 was lower when compared to controls...
2017: PloS One
https://www.readbyqxmd.com/read/28794380/tumor-lysis-syndrome-after-the-administration-of-ruxolitinib-in-a-patient-with-post-polycythemia-vera-myelofibrosis
#5
Megumi Koshiishi, Yuki Sueki, Ichiro Kawashima, Kei Nakajima, Toru Mitsumori, Keita Kirito
The development of tumor lysis syndrome (TLS) in association with treatment for myeloproliferative neoplasms (MPNs) is relatively rare. We herein present the case of a post-polycythemia vera (PV) myelofibrosis patient with massive splenomegaly who developed laboratory TLS after treatment with ruxolitinib, a potent JAK1/JAK2 inhibitor. She also exhibited a rapid reduction of spleen volume. Our present case suggests the potential risk of TLS development after ruxolitinib treatment, particularly in patients with massive splenomegaly...
August 10, 2017: Internal Medicine
https://www.readbyqxmd.com/read/28791654/pharmacotherapy-of-myelofibrosis
#6
REVIEW
Douglas Tremblay, Bridget Marcellino, John Mascarenhas
Myelofibrosis (MF) is a myeloproliferative neoplasm that is pathologically characterized by bone marrow myeloproliferation, reticulin and collagen fibrosis, and extramedullary hematopoiesis. Constitutive activation of the Janus associated kinase (JAK)-signal transducers and activators of transcription signaling pathway with resultant elevation in pro-inflammatory cytokine levels is the pathogenic hallmark of MF. JAK inhibitors, namely ruxolitinib, have been successful in alleviating symptoms and reducing splenomegaly, but therapy-related myelosuppression has led to the further development of highly selective JAK2 inhibitors...
August 8, 2017: Drugs
https://www.readbyqxmd.com/read/28780729/the-impact-of-myeloproliferative-neoplasms-mpns-on-patient-quality-of-life-and-productivity-results-from-the-international-mpn-landmark-survey
#7
Claire N Harrison, Steffen Koschmieder, Lynda Foltz, Paola Guglielmelli, Tina Flindt, Michael Koehler, Jonathan Mathias, Norio Komatsu, Robert N Boothroyd, Amber Spierer, Julian Perez Ronco, Gavin Taylor-Stokes, John Waller, Ruben A Mesa
Myelofibrosis (MF), polycythemia vera (PV), and essential thrombocythemia (ET) are myeloproliferative neoplasms (MPNs) associated with high disease burden, reduced quality of life (QOL), and shortened survival. To assess how MPNs affect patients, we conducted a global MPN Landmark survey. This online survey of patients with MPNs and physicians was conducted in Australia, Canada, Germany, Japan, Italy, and the United Kingdom. The survey measured MPN-related symptoms and the impact of MPNs on QOL and the ability to work as well as disease-management strategies...
August 5, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28780601/elevated-plasma-levels-of-procoagulant-microparticles-are-a-novel-risk-factor-for-thrombosis-in-patients-with-myeloproliferative-neoplasms
#8
Yasuhiro Taniguchi, Hirokazu Tanaka, Espinoza J Luis, Kazuko Sakai, Takahiro Kumode, Keigo Sano, Kentarou Serizawa, Shinya Rai, Yasuyoshi Morita, Hitoshi Hanamoto, Kazuo Tsubaki, Kazuto Nishio, Itaru Matsumura
Myeloproliferative neoplasms (MPNs), including polycythemia vera and essential thrombocythemia, are frequently associated with thrombotic complications. Prevention of thrombotic events is thus a primary aim of the current treatment for these disorders. Although it is known that microparticles (MPs), which are small vesicles released from cell membranes and circulate in the blood, directly contribute to thrombosis via their procoagulant activity, potential associations between plasma levels of MPs and the risk of thrombotic events in MPNs have not been reported...
August 5, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28775205/therapy-related-hematological-malignancies-after-peptide-receptor-radionuclide-therapy-with-177-lu-dota-octreotate-incidence-course-predicting-factors-in-patients-with-gep-nets
#9
Hendrik Bergsma, Kirsten van Lom, Mark Konijnenberg, Boen Kam, Jaap Teunissen, Wouter de Herder, Eric Krenning, Dik Kwekkeboom
Peptide Receptor Radionuclide Therapy (PRRT) may induce long-term toxicity to the bone marrow (BM). The aim of this study was to analyze persistent dysfunction of the hematopoietic system after PRRT with (177)Lu-DOTATATE in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Methods: The incidence and course of persistent hematological dysfunction (PHD) was analyzed in 274 (=GEP-NET) out of 367 patients with somatostatin receptor-positive tumors. PHD was defined as diagnosis of Myelodysplastic Syndrome (MDS), Acute Myeloid Leukemia (AML), Myeloproliferative Neoplasms (MPN), Myelodysplastic/Myeloproliferative neoplasms (MDS/MPN) or otherwise unexplained cytopenia (for more than 6 months)...
August 3, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28774880/a-randomized-phase-ii-study-of-low-dose-decitabine-versus-low-dose-azacitidine-in-lower-risk-mds-and-mds-mpn
#10
Elias Jabbour, Nicholas J Short, Guillermo Montalban-Bravo, Xuelin Huang, Carlos Bueso-Ramos, Wei Qiao, Hui Yang, Chong Zhao, Tapan Kadia, Gautam Borthakur, Naveen Pemmaraju, Koji Sasaki, Zeev Estrov, Jorge Cortes, Farhad Ravandi, Yesid Alvarado, Rami Komrokji, Mikkael A Sekeres, David P Steensma, Amy DeZern, Gail Roboz, Hagop Kantarjian, Guillermo Garcia-Manero
BACKGROUND: Hypomethylating agents (HMAs) improve survival in patients with higher-risk myelodysplastic syndromes (MDS) but are less well-studied in lower-risk disease. We compared the safety and efficacy of low-dose decitabine versus low-dose azacitidine in this group of patients. METHODS: Adults with low- or intermediate-1-risk MDS or MDS/myeloproliferative neoplasm (MPN), including chronic myelomonocytic leukemia, by the International Prognostic Scoring System were randomized using a Bayesian adaptive design to receive either azacitidine 75 mg/m(2) IV/SC daily or decitabine 20 mg/m(2) IV daily for 3 consecutive days on a 28-day cycle...
August 3, 2017: Blood
https://www.readbyqxmd.com/read/28771058/myelodysplastic-and-myeloproliferative-neoplasms-updates-on-the-overlap-syndromes
#11
Swapna Thota, Aaron T Gerds
Myelodysplastic and myeloproliferative neoplasms (MDS/MPN) is a rare and distinct group of myeloid neoplasms with overlapping MDS and MPN features. Next generation sequencing studies have led to an improved understanding of MDS/MPN disease biology by identifying recurrent somatic mutations. Combining the molecular findings to patho-morphologic features has improved the precision of diagnosis and prognostic models in MDS/MPN. We discuss and highlight these updates in MDS/MPN nomenclature and diagnostic criteria per revised 2016 WHO classification of myeloid neoplasms in this article...
August 3, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28770949/treatment-of-patients-with-primary-myelofibrosis-using-dasatinib
#12
Q-L Song, B Zhang, Y Xu, R-X Xia, X-H Lu, Z-X Pei, Q-W Xu, W-Y Li, Z-D Li
OBJECTIVE: Primary myelofibrosis (PMF) is a chronic clonal myeloproliferative neoplasm. It is associated with a poor prognosis, with a median survival time of approximately five years. Thus far, there are no specific targeted drugs for PMF. In this study, we evaluated the efficacy and safety of dasatinib, a second-generation tyrosine kinase inhibitor, in six PMF patients. PATIENTS AND METHODS: From June 1, 2015 to February 29, 2016, six patients with PMF in our department were enrolled into this trial...
July 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28762112/targeted-next-generation-sequencing-identifies-clinically-relevant-mutations-in-patients-with-chronic-neutrophilic-leukemia-at-diagnosis-and-blast-crisis
#13
S E Langabeer, K Haslam, J Kelly, J Quinn, R Morrell, E Conneally
PURPOSE: Chronic neutrophilic leukemia is a rare form of myeloproliferative neoplasm characterized by mature neutrophil hyperleukocytosis. The majority of patients harbor somatic mutations of CSF3R gene and are potentially amenable to targeted therapy with JAK inhibitors. The incidence and clinical significance of additional mutations requires clarification. MATERIALS AND METHODS: A next-generation sequencing approach for myeloid malignancy-associated mutations was applied to diagnostic and matched blast crisis samples from four chronic neutrophilic leukemia patients...
July 31, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/28760304/diagnostic-prognostic-and-predictive-utility-of-recurrent-somatic-mutations-in-myeloid-neoplasms
#14
REVIEW
Umang Patel, Rajyalakshmi Luthra, L Jeffrey Medeiros, Keyur P Patel
The classification and risk stratification of myeloid neoplasms, including acute myeloid leukemia, myelodysplastic syndromes, myelodysplastic syndromes/myeloproliferative neoplasms, and myeloproliferative neoplasms, have increasingly been guided by molecular genetic abnormalities. Gene expression analysis and next-generation sequencing have led to the ever increasing discovery of somatic gene mutations in myeloid neoplasms. Mutations have been identified in genes involved in epigenetic modification, RNA splicing, transcription factors, DNA repair, and the cohesin complex...
July 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28760302/developmental-therapeutics-in-myeloproliferative-neoplasms
#15
REVIEW
Prithviraj Bose, Srdan Verstovsek
The unprecedented success of the Janus kinase (JAK) 1/2 inhibitor ruxolitinib in myelofibrosis (MF) provided much-needed impetus for clinical drug development for the Philadelphia chromosome-negative myeloproliferative neoplasms. The survival benefit conferred by this agent, along with its marked efficacy with regard to spleen volume and symptom reduction, have made ruxolitinib the cornerstone of drug therapy in MF. However, there remain significant unmet needs in the treatment of patients with MF, and many novel classes of agents continue to be investigated in efforts to build on the progress made with ruxolitinib...
July 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28760301/the-challenge-of-treating-myelodysplastic-syndromes-myeloproliferative-neoplasms
#16
REVIEW
Brittany Knick Ragon, Michael R Savona
Myelodysplastic syndromes/myeloproliferative neoplasms (MDS/MPN) comprise a spectrum of myeloid disorders with both dysplastic and proliferative features, arising from hematopoietic stem cells. MDS/MPN are neither MDS nor MPN but a distinct World Health Organization-defined subclassification of diseases that, by definition, do not arise from a pre-existing MDS or MPN, inherently creating diagnostic and therapeutic challenges. Appropriately recognizing and classifying MDS/MPN is paramount for appropriately formulating treatment strategies and accurate prognostication...
July 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28758099/platelet-expression-of-pkcepsilon-oncoprotein-in-myelofibrosis-is-associated-with-disease-severity-and-thrombotic-risk
#17
Elena Masselli, Cecilia Carubbi, Giulia Pozzi, Silvia Martini, Franco Aversa, Daniela Galli, Giuliana Gobbi, Prisco Mirandola, Marco Vitale
BACKGROUND: Myelofibrosis (MF) is the most aggressive Philadelphia-negative chronic myeloproliferative neoplasm (MPN) with high morbidity and mortality due to thrombo-hemorrhagic complications and leukemic transformation. MF is characterized by profound alterations of megakaryocytopoiesis, with consequent abnormalities in platelet number and function. We recently showed that the overexpression of the oncoprotein PKCepsilon plays a key role in the aberrant differentiation of MF megakaryocyte clone and that its levels correlate with disease burden...
July 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28751440/exposure-response-of-veliparib-to-inform-phase%C3%A2-ii-trial-design-in-refractory-or-relapsed-patients-with-hematological-malignancies
#18
Shailly Mehrotra, Mathangi Gopalakrishnan, Jogarao Gobburu, Jiuping Jay Ji, Jacqueline M Greer, Richard L Piekarz, Judith Karp, Keith W Pratz, Michelle A Rudek
Purpose: A phase I trial of veliparib in combination with topotecan plus carboplatin (T+C) demonstrated 33% objective response rate in patients with hematological malignancies. The objective is to perform exposure-response analysis to inform the phase II trial design. <p>Experimental Design: Pharmacokinetic, efficacy and safety data from 95 patients, who were administered 10 to 100 mg BID doses of veliparib for either 8, 14 or 21 days with T+C, were utilized for exposure-efficacy (objective response and overall survival) and exposure-safety (≥Grade 3  mucositis) analysis...
July 27, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28747560/germline-variations-at-jak2-tert-hbs1l-myb-and-mecom-and-the-risk-of-myeloproliferative-neoplasms-in-taiwanese-population
#19
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...
July 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28745329/involvement-of-maf-spp1-axis-in-the-development-of-bone-marrow-fibrosis-in-pmf-patients
#20
S Ruberti, E Bianchi, P Guglielmelli, S Rontauroli, G Barbieri, L Tavernari, T Fanelli, R Norfo, V Pennucci, G C Fattori, C Mannarelli, N Bartalucci, B Mora, L Elli, M A Avanzini, C Rossi, S Salmoiraghi, R Zini, S Salati, Z Prudente, V Rosti, F Passamonti, A Rambaldi, S Ferrari, E Tagliafico, A M Vannucchi, R Manfredini
Primary Myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by hyperplastic megakaryopoiesis and myelofibrosis. We recently described the upregulation of MAF in PMF CD34+ hematopoietic progenitor cells (HPCs) compared to healthy donor. Here we demonstrated that MAF is also upregulated in PMF compared to Essential Thrombocytemia (ET) and Polycytemia Vera (PV) HPCs. MAF overexpression and knockdown experiments shed some light into the role of MAF in PMF pathogenesis, by demonstrating that MAF favours the megakaryocyte and monocyte/macrophage commitment of HPCs and leads to the increased expression of proinflammatory and profibrotic mediators...
July 12, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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