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JAK2 V617F

Ying Pang, Garima Gupta, Chunzhang Yang, Herui Wang, Thanh-Truc Huynh, Ziedulla Abdullaev, Svetlana D Pack, Melanie J Percy, Terence R J Lappin, Zhengping Zhuang, Karel Pacak
BACKGROUND: The role of the hypoxia signaling pathway in the pathogenesis of pheochromocytoma/paraganglioma (PPGL)-polycythemia syndrome has been elucidated. Novel somatic mutations in hypoxia-inducible factor type 2A (HIF2A) and germline mutations in prolyl hydroxylase type 1 and type 2 (PHD1 and PHD2) have been identified to cause upregulation of the hypoxia signaling pathway and its target genes including erythropoietin (EPO) and its receptor (EPOR). However, in a minority of patients presenting with this syndrome, the genetics and molecular pathogenesis remain unexplained...
March 13, 2018: BMC Cancer
M Palova, T Szotkowski, A Hlusi, K Indrak, J Navratilova, M Divoka, T Papajik
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. An integral part of laboratory tests carried out in this disease group is detecting the presence of mutations in the Janus kinase 2 gene at position 617 (JAK2 V617F) and in the gene encoding for the receptor for thrombopoietin (myeloproliferative leukemia virus oncogene, MPL) found in approximately 60% of PMF patients...
2018: Neoplasma
Helena Claerhout, Sophie Van Aelst, Celine Melis, Thomas Tousseyn, Olivier Gheysens, Peter Vandenberghe, Daan Dierickx, Nancy Boeckx
OBJECTIVE: Diagnosing myeloid sarcoma remains challenging and we aimed to provide clinicopathological features to facilitate diagnosis. METHOD: Clinicopathological data from 41 patients with de novo and 31 with secondary myeloid sarcoma were reviewed. RESULTS: Most de novo cases presented with isolated myeloid sarcoma (n=19) or myeloid sarcoma with concurrent acute myeloid leukemia (n=15). Most secondary cases presented after acute myeloid leukemia (n=11), myeloproliferative neoplasm (n=9) or myelodysplastic syndrome (n=8)...
March 12, 2018: European Journal of Haematology
Jerry L Spivak
Polycythemia vera (PV) is the most common myeloproliferative neoplasm (MPN), the ultimate phenotype of the JAK2 V1617F mutation, the MPN with the highest incidence of thromboembolic complications, which usually occur early in the course of the disease, and the only MPN in which erythrocytosis occurs. The classical presentation of PV is characterized by erythrocytosis, leukocytosis, and thrombocytosis, often with splenomegaly and occasionally with myelofibrosis, but it can also present as isolated erythrocytosis with or without splenomegaly, isolated thrombocytosis or isolated leukocytosis, or any combination of these...
March 7, 2018: Current Treatment Options in Oncology
K Lewandowski, M Gniot, M Wojtaszewska, Z Kanduła, R Becht, E Paczkowska, E Mędraś, E Wasilewska, M Iwoła
INTRODUCTION: There are 7 designated conditions under the category of myeloproliferative neoplasms (MPN), including chronic myelogenous leukemia (CML) and classical MPN, that is, polycythemia vera (PV), essential thrombocythaemia (ET), and primary myelofibrosis (PMF). Recently, reports about Philadelphia and JAK2 V617F-positive MPN cases have been described in literature. The coexistence of different molecular defects may change the clinical and laboratory manifestation of MPN and may result in an inappropriate interpretation of the response to treatment with tyrosine kinase inhibitors in CML patients...
March 6, 2018: International Journal of Laboratory Hematology
A A Silyutina, I I Gin, S S Prikhod'ko, S V Zhuk, P A Butylin, A Yu Zaritskii
We analyzed previously generated stable monocyte-derived cell line carrying mutation JAK2 V617F. Evaluation of the expression of pro- and antifibrotic factors revealed changes in the production of MMPs and their inhibitors, growth factors, galectin-3, and pentraxin 3 in cells carrying mutation JAK2 in comparison with control non-modified cells.
March 5, 2018: Bulletin of Experimental Biology and Medicine
João Agostinho Machado-Neto, Bruna Alves Fenerich, Renata Scopim-Ribeiro, Christopher A Eide, Juan Luiz Coelho-Silva, Carlos Roberto Porto Dechandt, Jaqueline Cristina Fernandes, Ana Paula Nunes Rodrigues Alves, Priscila Santos Scheucher, Belinda Pinto Simões, Luciane Carla Alberici, Lorena Lôbo de Figueiredo Pontes, Cristina E Tognon, Brian J Druker, Eduardo Magalhães Rego, Fabiola Traina
The recurrent gain-of-function JAK2V617F mutation confers growth factor-independent proliferation for hematopoietic cells and is a major contributor to the pathogenesis of myeloproliferative neoplasms (MPN). The lack of complete response in most patients treated with the JAK1/2 inhibitor ruxolitinib indicates the need for identifying novel therapeutic strategies. Metformin is a biguanide that exerts selective antineoplastic activity in hematological malignancies. In the present study, we investigate and compare effects of metformin and ruxolitinib alone and in combination on cell signaling and cellular functions in JAK2V617F -positive cells...
February 22, 2018: Cell Death & Disease
Vanya Jaitly, Wei Wang
No abstract text is available yet for this article.
February 22, 2018: Blood
Alessandro Prestipino, Alica J Emhardt, Konrad Aumann, David O'Sullivan, Sivahari P Gorantla, Sandra Duquesne, Wolfgang Melchinger, Lukas Braun, Slavica Vuckovic, Melanie Boerries, Hauke Busch, Sebastian Halbach, Sandra Pennisi, Teresa Poggio, Petya Apostolova, Pia Veratti, Michael Hettich, Gabriele Niedermann, Mark Bartholomä, Khalid Shoumariyeh, Jonas S Jutzi, Julius Wehrle, Christine Dierks, Heiko Becker, Annette Schmitt-Graeff, Marie Follo, Dietmar Pfeifer, Jan Rohr, Sebastian Fuchs, Stephan Ehl, Frederike A Hartl, Susana Minguet, Cornelius Miething, Florian H Heidel, Nicolaus Kröger, Ioanna Triviai, Tilman Brummer, Jürgen Finke, Anna L Illert, Eliana Ruggiero, Chiara Bonini, Justus Duyster, Heike L Pahl, Steven W Lane, Geoffrey R Hill, Bruce R Blazar, Nikolas von Bubnoff, Erika L Pearce, Robert Zeiser
Recent evidence has revealed that oncogenic mutations may confer immune escape. A better understanding of how an oncogenic mutation affects immunosuppressive programmed death ligand 1 (PD-L1) expression may help in developing new therapeutic strategies. We show that oncogenic JAK2 (Janus kinase 2) activity caused STAT3 (signal transducer and activator of transcription 3) and STAT5 phosphorylation, which enhanced PD-L1 promoter activity and PD-L1 protein expression in JAK2V617F -mutant cells, whereas blockade of JAK2 reduced PD-L1 expression in myeloid JAK2V617F -mutant cells...
February 21, 2018: Science Translational Medicine
Tshiphiri Senamela, Marleen Kock, Piet Becker, Joachim J C Potgieter
The purpose of this study was to develop a real time polymerase chain reaction (PCR) assay for the detection of the JAK2 V617F mutation that could be used in diagnostic laboratories. Sanger sequencing and a newly developed locked nucleic-acid, real-time PCR assay were used to detect the JAK2 V617F mutation. There was 100% agreement between the sequencing and PCR analysis. Both assays were able to detect the mutation in all 24 of the 60 test specimens harbouring the mutation.
2018: African Journal of Laboratory Medicine
Dian Zhou, Wei Chen, Kai-Lin Xu
Essential thrombocythemia(ET) is one of the Ph chromosome-negative myeloproliferative neoplasms. Some studies discovered that the mutation of JAK2 V617F existed in 50%-70% patients with ET. Recently, many significant advances in researches about pathogenesis of ET, such as mutations of JAK2V617F, MPL, CALR and other related mutation; the epigenetic abnomalities in incidence of ET; the changes of bone marrow microenvironment of ET and the regulation of related cytokines were obtained. In this article, the advances of above mentioned aspects of ET are summarized...
February 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
Jun-Xiu Liu, Wei Chen, Kai-Lin Xu
Myelofibrosis(MF) is a type of myeloprolifirative neoplasms which is difficult to be treated. With the discovery of V617F mutation site in Janus kinase 2 (JAK2), JAK inhibitor provides a new treatment strategy for patients with myelofibrosis. Since 2011 the FDA in USA approved the first generation of JAK inhibitor Ruxolitinib for marketing, a growing number of JAK inhibitors have been entering into the clinical trials and showed a certain clinical efficacy. On the one hand, some JAK inhibitors for single application can effectively relieve the clinical symptoms of patients with myelofibrosis, slow down disease progression, and prolong the survival; on the other hand, JAK inhibitor can also be applied in combination with traditional or other new targeted drugs for MF patients, even during the allogenetic hematopoietic stem cell transplantation, thus providing more choices for targeted therapy on the patients with myelofibrosis...
February 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
Stephen E Langabeer
No abstract text is available yet for this article.
2018: EXCLI Journal
Monia Marchetti, Alessandra Carobbio, Enrica Capitoni, Tiziano Barbui
Patients with a Ph-negative myeloproliferative neoplasm (MPN) may harbor or develop lymphoproliferative disorders (LPD), however, the clinical and molecular determinants of MPN and LPD co-occurrence are still uncertain. In order to systematically pool the available knowledge, we conducted a scoping review of literature published since January 2005 and analyzed single-patient clinical data from 50 papers reporting 214 individuals harboring both MPN and LPD. Patients had been diagnosed essential thrombocythemia (44%), polycythemia vera (29%) or myelofibrosis (23%) at a median age of 67 years (26-94): half of them incurred a LPD after a median of 72 months from MPN diagnosis, while in 20% the LPD diagnosis was antecedent or synchronous...
January 27, 2018: American Journal of Hematology
Víctor Manuel Sández Montagut, Álvaro Giráldez Gallego, Guilermo Ontanilla Clavijo
We report a case of a regenerative nodular hyperplasia with a portal vein cavernomatosis with a subsequent progression to symptomatic, occlusive thrombosis of the superior mesenteric vein. A thorough investigation resulted in a final diagnosis of primary myelofibrosis associated with the V617F mutation in the JAK2 gene.
January 25, 2018: Revista Española de Enfermedades Digestivas
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
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
Thomas McKerrell, Naomi Park, Jianxiang Chi, Grace Collord, Thaidy Moreno, Hannes Ponstingl, Joao Dias, Petroula Gerasimou, Kiki Melanthiou, Chrystalla Prokopiou, Marios Antoniades, Ignacio Varela, Paul A Costeas, George S Vassiliou
No abstract text is available yet for this article.
June 13, 2017: Blood Advances
Roberta Zini, Paola Guglielmelli, Daniela Pietra, Elisa Rumi, Chiara Rossi, Sebastiano Rontauroli, Elena Genovese, Tiziana Fanelli, Laura Calabresi, Elisa Bianchi, Simona Salati, Mario Cazzola, Enrico Tagliafico, Alessandro M Vannucchi, Rossella Manfredini
Polycythemia vera (PV) and essential thrombocythemia (ET) are Philadelphia-negative myeloproliferative neoplasms (MPNs) characterized by erythrocytosis and thrombocytosis, respectively. Approximately 95% of PV and 50-70% of ET patients harbor the V617F mutation in the exon 14 of JAK2 gene, while about 20-30% of ET patients carry CALRins5 or CALRdel52 mutations. These ET CALR-mutated subjects show higher platelet count and lower thrombotic risk compared to JAK2-mutated patients. Here, we showed that CALR-mutated and JAK2V617F-positive CD34+ cells display different gene and miRNA expression profiles...
December 8, 2017: Blood Cancer Journal
Eunyoung Lee, Kyoung Joo Lee, Hyein Park, Jin Young Chung, Mi Na Lee, Myung Hee Chang, Jongha Yoo, Hyewon Lee, Sun Young Kong, Hyeon Seok Eom
BACKGROUND: JAK2 V617F is the most common mutation in myeloproliferative neoplasms (MPNs) and is a major diagnostic criterion. Mutation quantification is useful for classifying patients with MPN into subgroups and for prognostic prediction. Droplet digital PCR (ddPCR) can provide accurate and reproducible quantitative analysis of DNA. This study was designed to verify the correlation of ddPCR with pyrosequencing results in the diagnosis of MPN and to investigate clinical implications of the mutational burden...
March 2018: Annals of Laboratory Medicine
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