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https://www.readbyqxmd.com/read/27930945/a-phase-ii-study-of-panobinostat-in-patients-with-primary-myelofibrosis-pmf-and-post-polycythemia-vera-essential-thrombocythemia-myelofibrosis-post-pv-et-mf
#1
John Mascarenhas, Lonette Sandy, Min Lu, James Yoon, Bruce Petersen, David Zhang, Fei Ye, Carrie Newsom, Vesna Najfeld, Tsivia Hochman, Judith D Goldberg, Ronald Hoffman
Myelofibrosis is a chronic and progressive myeloproliferative neoplasm characterized by anemia, splenomegaly, debilitating symptoms and leukemic transformation. Ruxolitinib, an oral JAK1/2 inhibitor, is highly effective in ameliorating systemic symptoms and reducing splenomegaly. Current clinical research is focused on the evaluation of agents based on pre-clinical rationale that can result in disease course modification. Panobinostat is a pan-histone deacetylase inhibitor that has demonstrated clinical activity as a single agent in early phase trials of myelofibrosis...
November 30, 2016: Leukemia Research
https://www.readbyqxmd.com/read/27930632/highlights-in-polycythemia-vera-from-the-2016-eha-congress
#2
Srdan Verstovsek
Meeting highlights from the European Hematology Association congress, June 9-12, Copenhagen, Denmark.
October 2016: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/27929530/effects-of-delayed-cord-clamping-on-residual-placental-blood-volume-hemoglobin-and-bilirubin-levels-in-term-infants-a-randomized-controlled-trial
#3
J S Mercer, D A Erickson-Owens, J Collins, M O Barcelos, A B Parker, J F Padbury
OBJECTIVE: The objective of the study was to measure the effects of a 5-min delay (DCC) versus immediate cord clamping (ICC) on residual placental blood volume (RPBV) at birth, and hemoglobin and serum bilirubin at 24 to 48 h of age. STUDY DESIGN: In this prospective randomized controlled trial, 73 women with term (37 to 41 weeks) singleton fetuses were randomized to DCC (⩾5 min; n=37) or ICC (<20 s; n=36). RESULTS: Maternal and infant demographics were not different between the groups...
December 8, 2016: Journal of Perinatology: Official Journal of the California Perinatal Association
https://www.readbyqxmd.com/read/27924369/bone-marrow-microvessel-density-and-plasma-angiogenic-factors-in-myeloproliferative-neoplasms-clinicopathological-and-molecular-correlations
#4
Danijela Lekovic, Mirjana Gotic, Radek Skoda, Bojana Beleslin-Cokic, Natasa Milic, Olivera Mitrovic-Ajtic, Ronny Nienhold, Dijana Sefer, Tijana Suboticki, Marijana Buac, Dragana Markovic, Milos Diklic, Vladan P Cokic
Increased angiogenesis in BCR-ABL1 negative myeloproliferative neoplasms (MPNs) has been recognized, but its connection with clinical and molecular markers needs to be defined. The aims of study were to (1) assess bone marrow (BM) angiogenesis measured by microvessel density (MVD) using CD34 and CD105 antibodies; (2) analyze correlation of MVD with plasma angiogenic factors including vascular endothelial growth factor, basic fibroblast growth factor, and interleukin-8; (3) examine the association of MVD with clinicopathological and molecular markers...
December 6, 2016: Annals of Hematology
https://www.readbyqxmd.com/read/27924280/the-role-of-the-exon-13-g571s-jak2-mutation-in-myeloproliferative-neoplasms
#5
Burak Bahar, Kevin Barton, Ameet R Kini
The exon 14 JAK2 V617F mutation has been well established as a driver mutation in polycythemia vera (PV) and other myeloproliferative neoplasms. JAK2 exon 12 mutations have also been implicated in PV, although patients with these mutations may show isolated erythrocytosis. Recently additional JAK2point mutations have been described-all in regions encoding the pseudokinase domain that regulates the tyrosine kinase activity of JAK2. We present a case of a patient with erythrocytosis and an exon 13 G571S mutation, and discuss the putative role of this mutation in myeloproliferative neoplasms...
2016: Leukemia Research Reports
https://www.readbyqxmd.com/read/27919930/mir-17-20-controls-prolyl-hydroxylase-2-phd2-hypoxia-inducible-factor-1-hif1-to-regulate-pulmonary-artery-smooth-muscle-cell-proliferation
#6
Tianji Chen, Qiyuan Zhou, Haiyang Tang, Melike Bozkanat, Jason X-J Yuan, J Usha Raj, Guofei Zhou
BACKGROUND: Previously we found that smooth muscle cell (SMC)-specific knockout of miR-17~92 attenuates hypoxia-induced pulmonary hypertension. However, the mechanism underlying miR-17~92-mediated pulmonary artery SMC (PASMC) proliferation remains unclear. We sought to investigate whether miR-17~92 regulates hypoxia-inducible factor (HIF) activity and PASMC proliferation via prolyl hydroxylases (PHDs). METHODS AND RESULTS: We show that hypoxic sm-17~92(-/-) mice have decreased hematocrit, red blood cell counts, and hemoglobin contents...
December 5, 2016: Journal of the American Heart Association
https://www.readbyqxmd.com/read/27919526/factors-related-to-the-development-of-acquired-von-willebrand-syndrome-in-patients-with-essential-thrombocythemia-and-polycythemia-vera
#7
A Rottenstreich, G Kleinstern, S Krichevsky, D Varon, D Lavie, Y Kalish
OBJECTIVE: We characterized acquired von Willebrand syndrome (AVWS) among essential thrombocythemia (ET) and polycythemia vera (PV) patients. METHODS: A review of patients with ET or PV evaluated for AVWS. RESULTS: Of 116 patients with ET, 64 (55%) developed AVWS; of 57 with PV, 28 (49%) developed AVWS. Median platelet counts of ET and PV patients who developed AVWS were 920×10(9)/L and 679×10(9)/L, respectively (P=0.01). Of patients who developed AVWS, 69...
December 2, 2016: European Journal of Internal Medicine
https://www.readbyqxmd.com/read/27918575/high-serum-adiponectin-level-is-a-risk-factor-for-anemia-in-japanese-men-a-prospective-observational-study-of-1-029-japanese-subjects
#8
Kei Kohno, Hiroto Narimatsu, Yosuke Shiono, Ikuko Suzuki, Yuichi Kato, Ri Sho, Katsumi Otani, Kenichi Ishizawa, Hidetoshi Yamashita, Isao Kubota, Yoshiyuki Ueno, Takeo Kato, Akira Fukao, Takamasa Kayama
Erythroid abnormalities including anemia and polycythemia are often observed in the general clinical setting. Because recent studies reported that adiponectin negatively affects hematopoiesis, we performed a prospective observational study to assess the relationship between anemia and adiponectin, as well as other parameters, in 1029 Japanese subjects (477 men and 552 women) 40 years of age and older. Body measurements, blood tests, and nutrition intake studies were performed at baseline, and 5 to 7 years later (follow-up)...
2016: PloS One
https://www.readbyqxmd.com/read/27913526/update-from-the-latest-who-classification-of-mpns-a-user-s-manual
#9
Francesco Passamonti, Margherita Maffioli
The 2016 multiparameter World Health Organization (WHO) classification for Philadelphia-negative myeloproliferative neoplasms (MPNs) integrates clinical features, morphology, and genetic data to diagnose polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). The main novelties are: (1) the reduction of the hemoglobin (Hb) level threshold to diagnose PV, now established at 16.5 g/dL for men and 16 g/dL for women (based on the identification of MPN patients with PV-consistent bone marrow [BM] features and a Hb level lower than that established in the 2008 WHO classification for PV); (2) the recognition of prefibrotic/early PMF, distinguishable from ET on the basis of BM morphology, an entity having a higher tendency to develop overt myelofibrosis or acute leukemia, and characterized by inferior survival; (3) the central role of BM morphology in the diagnosis of ET, prefibrotic/early PMF, PMF, and PV with borderline Hb values; megakaryocyte number and morphology (typical in ET, atypical in both PMF forms) accompanied by a new distinction of reticulin fibrosis grade in PMF (grade 1 in prefibrotic/early PMF and grade 2-3 in PMF) constitute diagnostic criteria; and (4) the inclusion of all mutually exclusive MPN driver mutations (JAK2, CALR, and MPL) as major diagnostic criteria in ET and PMF; 10% to 15% of these patients are triple negative, and in these cases the search for an additional clonal marker (eg, mutations in ASXL1, EZH2, TET2, IDH1/IDH2, SRSF2, and SF3B1) is warranted...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27911124/the-impact-of-interferon-alpha2-on-hla-genes-in-patients-with-polycythemia-vera-and-related-neoplasms
#10
Vibe Skov, Caroline Hasselbalch Riley, Mads Thomassen, Lasse Kjær, Thomas Stauffer Larsen, Ole Weis Bjerrum, Torben A Kruse, Hans Carl Hasselbalch
Gene expression profiling in Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) have unraveled significant deregulation of several immune and inflammation genes of potential importance for clonal evolution. Other mechanisms might be downregulation of major histocompatibility class I and II genes used by tumor cells to escape antitumor T-cell-mediated immune responses. Several genes encoding human leukocyte antigen (HLA) class I and II molecules have been shown to be significantly downregulated...
December 2, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27896259/prenatal-diagnosis-of-spontaneous-twin-anemia-polycythemia-sequence-and-postnatal-examination-of-placental-vascular-anastomoses
#11
Jin Young Bae, Jin Ju Oh, Seong Yeon Hong
Twin anemia-polycythemia sequence (TAPS) is characterized by a wide discrepancy of hemoglobin between two monochorionic fetuses without sign of twin oligo-polyhydramnios sequence. A primiparous woman with monochorionic diamniotic twin transferred for preterm labor. Ultrasonographic evaluation at 32+3 weeks of gestation revealed increased middle cerebral artery-peak systolic velocity (77.4 cm/sec, 1.69 multiples of median) in donor and decreased in recipient twin (36.4 cm/sec, 0.79 multiples of median), the twin was diagnosed with TAPS...
November 2016: Obstetrics & Gynecology Science
https://www.readbyqxmd.com/read/27892678/characterization-and-prognosis-significance-of-jak2-v617f-mpl-and-calr-mutations-in-philadelphia-negative-myeloproliferative-neoplasms
#12
Roongrudee Singdong, Teerapong Siriboonpiputtana, Takol Chareonsirisuthigul, Adcharee Kongruang, Nittaya Limsuwanachot, Tanasan Sirirat, Suporn Chuncharunee, Budsaba Rerkamnuaychoke
Background: The discovery of somatic acquired mutations of JAK2 (V617F) in Philadelphia-negative myeloproliferative neoplasms (Ph-negative MPNs) including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) has not only improved rational disease classification and prognostication but also brings new understanding insight into the pathogenesis of diseases. Dosage effects of the JAK2 (V617F) allelic burden in Ph-negative MPNs may partially influence clinical presentation, disease progression, and treatment outcome...
January 10, 2016: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/27892526/comprehensive-gene-expression-meta-analysis-and-integrated-bioinformatic-approaches-reveal-shared-signatures-between-thrombosis-and-myeloproliferative-disorders
#13
Prabhash Kumar Jha, Aatira Vijay, Anita Sahu, Mohammad Zahid Ashraf
Thrombosis is a leading cause of morbidity and mortality in patients with myeloproliferative disorders (MPDs), particularly polycythemia vera (PV) and essential thrombocythemia (ET). Despite the attempts to establish a link between them, the shared biological mechanisms are yet to be characterized. An integrated gene expression meta-analysis of five independent publicly available microarray data of the three diseases was conducted to identify shared gene expression signatures and overlapping biological processes...
November 28, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27889725/fluid-supplementation-versus-no-fluid-supplementation-in-late-preterm-and-term-neonates-with-asymptomatic-polycythemia-a-randomized-controlled-trial
#14
Mangalabharathi Sundaram, Sourabh Dutta, Anil Narang
OBJECTIVE: To compare supplemental intravenous fluids with no supplementation in asymptomatic polycythemic late preterm and term neonates. METHODS: 55 infants with venous haematocrit of 65-75 were randomly allocated to receive either 25 mL/kg IV normal saline over 6-8 hours or routine fluids. They were followed up for 48 hours. RESULTS: There was no significant difference between fluid supplementation and control groups regarding need for partial exchange transfusion [6/27 (22...
November 15, 2016: Indian Pediatrics
https://www.readbyqxmd.com/read/27884974/from-leeches-to-personalized-medicine-evolving-concepts-in-the-management-of-polycythemia-vera
#15
Alessandro Maria Vannucchi
Polycythemia vera (PV), a clonal disorders of hematopoietic stem/progenitor cells that manifests with prevalent expansion of red cell mass, is the most frequent among chronic myeloproliferative neoplasms (MPN). It is characterized by a V617F point mutation in JAK2 exon 14 , or less common mutations in exon 12, in virtually all cases. The landmark discovery of autonomously activated JAK/STAT signaling pathway paved the way for the clinical development of the first target drug, the JAK1 and JAK2 inhibitor ruxolitinib, that is now approved for patients with resistance or intolerance to hydroxyurea...
November 24, 2016: Haematologica
https://www.readbyqxmd.com/read/27880982/safety-and-efficacy-of-ruxolitinib-in-splanchnic-vein-thrombosis-associated-with-myeloproliferative-neoplasms
#16
Lisa Pieri, Chiara Paoli, Umberto Arena, Fabio Marra, Fabio Mori, Mery Zucchini, Stefano Colagrande, Alessandro Castellani, Arianna Masciulli, Vittorio Rosti, Valerio De Stefano, Silvia Betti, Guido Finazzi, Maria Luisa Ferrari, Elisa Rumi, Marco Ruggeri, Ilaria Nichele, Paola Guglielmelli, Rajmonda Fjerza, Carmela Mannarelli, Tiziana Fanelli, Lucia Merli, Giuditta Corbizi Fattori, Margherita Massa, Giuseppe Cimino, Alessandro Rambaldi, Giovanni Barosi, Mario Cazzola, Tiziano Barbui, Alessandro M Vannucchi
Splanchnic vein thrombosis (SVT) is one of the vascular complications of myeloproliferative neoplasms (MPN). We designed a phase 2 clinical trial to evaluate safety and efficacy of ruxolitinib in reducing splenomegaly and improving disease-related symptoms in patients with MPN-associated SVT. Patients, diagnosed with myelofibrosis in 12 cases, polycythemia vera in 5 and essential thrombocythemia in 4, received ruxolitinib for 24 weeks in the core study period. Spleen volume was assessed by magnetic resonance imaging (MRI) and splanchnic vein circulation by echo-Doppler analysis...
November 23, 2016: American Journal of Hematology
https://www.readbyqxmd.com/read/27875375/management-of-venous-thromboembolism-in-myeloproliferative-neoplasms
#17
Tiziano Barbui, Valerio De Stefano
PURPOSE OF REVIEW: Venous thromboembolism is frequent in chronic myeloproliferative neoplasms (MPN). The current strategy for its management includes cytoreductive therapy and antithrombotic prophylaxis, but many issues remain uncertain. In this review, the risk factors and prevention of recurrences will be discussed. RECENT FINDINGS: Around one-third of patients with polycythemia vera and essential thrombocythemia experience a major thrombosis at diagnosis or during follow-up...
November 21, 2016: Current Opinion in Hematology
https://www.readbyqxmd.com/read/27866579/polycythemia-and-thrombocytosis
#18
REVIEW
Aric Parnes, Arvind Ravi
Myeloproliferative neoplasms (MPNs) are diseases of excess cell proliferation from bone marrow precursors. Two classic MPNs, polycythemia vera (PV) and essential thrombocytosis (ET), are conditions of excess proliferation of red blood cells and platelets, respectively. Although PV and ET involve different cells in the myeloid lineage, their clinical presentations have shared features, consistent with overlapping mutations in growth factor signaling. The management of both diseases involves minimizing the risk of thrombotic and hemorrhagic complications...
December 2016: Primary Care
https://www.readbyqxmd.com/read/27861436/the-association-between-cyanosis-and-thromboelastometry-rotem-in-children-with-congenital-heart-defects-a-retrospective-cohort-study
#19
Marie-Laure Laskine-Holland, Walter H A Kahr, Lynn Crawford-Lean, Tilman Humpl, Osami Honjo, Celeste Foreman, Mehr Jain, James D O'Leary
BACKGROUND: Children with congenital heart defects (CHD) have quantitative and qualitative differences in coagulation compared with healthy children. Secondary to polycythemia and increased deformability of red blood cells, cyanosis may be an important confounding factor for altered whole-blood coagulation in this population with potential implications for interpreting intraoperative thromboelastometry (TEM) for children with CHD undergoing major surgery. The primary aim of the study was to evaluate the association between cyanosis in children with CHD and measures of whole-blood coagulation determined using TEM (ROTEM [Tem International, GmbH, Munich, Germany])...
November 17, 2016: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/27858230/efficacy-and-safety-of-jak-inhibitor-inc424-in-patients-with-primary-and-post-polycythemia-vera-or-post-essential-thrombocythemia-myelofibrosis-in-the-chinese-population
#20
Xin Du, Daobin Zhou
A phase II study (A2202) was performed to evaluate the efficacy and safety of JAK inhibitor ruxolitinib in 63 Chinese MF patients. Ruxolitinib was given twice a day (bid) at a starting dose of 15 mg (n = 25) or 20 mg (n = 38) based on a baseline platelet count. About 94.7% of the patients achieved a reduction in spleen size, 27.0% of which exhibited significant reduction (≥ 35%) at week 24. Significant improvement in debilitating constitutional symptoms, as assessed by MFSAF v2.0, was observed in patients treated with ruxolitinib...
November 17, 2016: Frontiers of Medicine
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