keyword
MENU ▼
Read by QxMD icon Read
search

Jak 2 mutation

keyword
https://www.readbyqxmd.com/read/28214593/jak-stat-pathway-directed-therapy-of-t-cell-leukemia-lymphoma-inspired-by-functional-and-structural-genomics
#1
REVIEW
Thomas A Waldmann
Abnormal activation of the γc cytokine JAK/STAT signaling pathway assessed by STAT3 or STAT5b phosphorylation was present in a proportion of many T-cell malignancies. Activating mutations of STAT3/STAT5b and JAK1/3 were present in some but not in all cases with constitutive signaling pathway activation. Using shRNA analysis pSTAT malignant T-cell lines were addicted to JAKs/STATs whether they were mutated or not. Activating JAK/STAT mutations were not sufficient to support leukemic cell proliferation but only augmented upstream pathway signals...
February 15, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28202754/jak-stat-signaling-pathways-and-inhibitors-affect-reversion-of-envelope-mutated-hiv-1
#2
Yudong Quan, Hongtao Xu, Yingshan Han, Thibault Mesplède, Mark A Wainberg
HIV can spread by both cell-free and cell-to-cell transmission. Here, we show that numerous of the amino acid changes in Env that are close to the CD4 binding pocket can affect HIV replication. We generated a number of mutant viruses that were unable to infect T cells as cell-free viruses but were nevertheless able to infect certain T cell lines as cell-associated viruses, followed by reversion to wild type. However, the activation of JAK-STAT signaling pathways caused inhibition of such cell-to-cell infection as well as the reversion of multiple HIV Env mutants that displayed differences in ability to bind to the CD4 receptor...
February 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28167612/jak-mutations-as-escape-mechanisms-to-anti-pd-1-therapy
#3
Aurelien Marabelle, Sandrine Aspeslagh, Sophie Postel-Vinay, Jean-Charles Soria
JAK mutations could be one of the primary escape mechanisms to anti-PD-1/PD-L1 immunotherapy via impaired IFNγ signaling in cancer cells and could be used to identify patients unlikely to benefit from these treatments. Cancer Discov; 7(2); 128-30. ©2017 AACR.See related article by Shin et al., p. 188.
February 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28157215/identification-of-a-genetically-defined-ultra-high-risk-group-in-relapsed-pediatric-t-lymphoblastic-leukemia
#4
P Richter-Pechańska, J B Kunz, J Hof, M Zimmermann, T Rausch, O R Bandapalli, E Orlova, G Scapinello, J C Sagi, M Stanulla, M Schrappe, G Cario, R Kirschner-Schwabe, C Eckert, V Benes, J O Korbel, M U Muckenthaler, A E Kulozik
In the search for genes that define critical steps of relapse in pediatric T-cell acute lymphoblastic leukemia (T-ALL) and can serve as prognostic markers, we performed targeted sequencing of 313 leukemia-related genes in 214 patients: 67 samples collected at the time of relapse and 147 at initial diagnosis. As relapse-specific genetic events, we identified activating mutations in NT5C2 (P=0.0001, Fisher's exact test), inactivation of TP53 (P=0.0007, Fisher's exact test) and duplication of chr17:q11.2-24.3 (P=0...
February 3, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28077299/anaplastic-lymphoma-kinase-alk-inhibitors-in-the-treatment-of-alk-driven-lung-cancers
#5
REVIEW
Robert Roskoski
Anaplastic lymphoma kinase is expressed in two-thirds of the anaplastic large-cell lymphomas as an NPM-ALK fusion protein. Physiological ALK is a receptor protein-tyrosine kinase within the insulin receptor superfamily of proteins that participates in nervous system development. The EML4-ALK fusion protein and four other ALK-fusion proteins play a fundamental role in the development in about 5% of non-small cell lung cancers. The amino-terminal portions of the ALK fusion proteins result in dimerization and subsequent activation of the ALK protein kinase domain that plays a key role in the pathogenesis of various tumors...
March 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28057939/activating-jak2-mutants-reveal-cytokine-receptor-coupling-differences-that-impact-outcomes-in-myeloproliferative-neoplasm
#6
H Yao, Y Ma, Z Hong, L Zhao, S A Monaghan, M-C Hu, Lj-S Huang
Janus tyrosine kinase 2 (JAK2) mediates downstream signaling of cytokine receptors in all hematological lineages, yet constitutively active JAK2 mutants are able to drive selective expansion of particular lineage(s) in myeloproliferative neoplasm (MPN). The molecular basis of lineage specificity is unclear. Here we show that three activating JAK2 mutants with similar kinase activities in vitro elicit distinctive MPN phenotypes in mice by differentially expanding erythroid vs. granulocytic precursors. Molecularly, this reflects the differential binding of JAK2 mutants to cytokine receptors EpoR and GCSFR in the erythroid vs granulocytic lineage and the creation of unique receptor/JAK2 complexes that generate qualitatively distinct downstream signals...
January 6, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28057739/aberrant-let7a-hmga2-signaling-activity-with-unique-clinical-phenotype-in-jak2-mutated-myeloproliferative-neoplasms
#7
Chih-Cheng Chen, Jie-Yu You, Jrhau Lung, Cih-En Huang, Yi-Yang Chen, Yu-Wei Leu, Hsing-Ying Ho, Chian-Pei Li, Chang-Hsien Lu, Kuan-Der Lee, Chia-Chen Hsu, Jyh-Pyng Gau
High mobility group AT-hook 2 (HMGA2) is an architectural transcriptional factor that is negatively regulated by Let-7 microRNA through binding to its 3-untranslated region (3-UTR). Transgenic mice expressing HMGA2 with a truncation of its 3-UTR has been shown to exhibit a myeloproliferative phenotype. To decipher the Let-7-HMGA2 axis in myeloproliferative neoplasms (MPN), we employed an in vitro model supplemented with clinical correlation. Ba/F3 cells with inducible JAK2V617F expression (Ton.JAK2.V617F cells) showed up-regulation of HMGA2 with concurrent let-7a repression...
January 5, 2017: Haematologica
https://www.readbyqxmd.com/read/28043820/kinase-signaling-and-targeted-therapy-for-primary-myelofibrosis
#8
REVIEW
Qiong Yang, John D Crispino, Qiang Jeremy Wen
The myeloproliferative neoplasms (MPNs) are somatic mutation-driven hematologic malignancies characterized by bone marrow fibrosis and the accumulation of atypical megakaryocytes with reduced polyploidization in the primary myelofibrosis subtype of the MPNs. Increasing evidence points to a dominant role of abnormal megakaryocytes in disease initiation and progression. Here we review the literature related to kinase signaling pathways relevant to megakaryocyte differentiation and proliferation, including Aurora A kinase, RhoA/ROCK, and JAK/STAT, as well as the activities of their targeted inhibitors in models of the disease...
December 30, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/27956542/myeloproliferative-neoplasms-version-2-2017-nccn-clinical-practice-guidelines-in-oncology
#9
Ruben Mesa, Catriona Jamieson, Ravi Bhatia, Michael W Deininger, Aaron T Gerds, Ivana Gojo, Jason Gotlib, Krishna Gundabolu, Gabriela Hobbs, Rebecca B Klisovic, Patricia Kropf, Sanjay R Mohan, Stephen Oh, Eric Padron, Nikolai Podoltsev, Daniel A Pollyea, Raajit Rampal, Lindsay A M Rein, Bart Scott, David S Snyder, Brady L Stein, Srdan Verstovsek, Martha Wadleigh, Eunice S Wang, Mary Anne Bergman, Kristina M Gregory, Hema Sundar
Myelofibrosis (MF), polycythemia vera (PV), and essential thrombocythemia (ET) are a group of heterogeneous disorders of the hematopoietic system collectively known as Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs). The diagnosis and the management of patients with MPNs have evolved since the identification of mutations that activate the JAK pathway (JAK2, CALR, and MPL mutations) and the development of targeted therapies has resulted in significant improvements in disease-related symptoms and quality of life...
December 2016: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/27919027/phosphorylation-of-janus-kinase-1-jak1-by-amp-activated-protein-kinase-ampk-links-energy-sensing-to-anti-inflammatory-signaling
#10
Claire Rutherford, Claire Speirs, Jamie J L Williams, Marie-Ann Ewart, Sarah J Mancini, Simon A Hawley, Christian Delles, Benoit Viollet, Ana P Costa-Pereira, George S Baillie, Ian P Salt, Timothy M Palmer
Adenosine 5'-monophosphate-activated protein kinase (AMPK) is a pivotal regulator of metabolism at cellular and organismal levels. AMPK also suppresses inflammation. We found that pharmacological activation of AMPK rapidly inhibited the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway in various cells. In vitro kinase assays revealed that AMPK directly phosphorylated two residues (Ser(515) and Ser(518)) within the Src homology 2 domain of JAK1. Activation of AMPK enhanced the interaction between JAK1 and 14-3-3 proteins in cultured vascular endothelial cells and fibroblasts, an effect that required the presence of Ser(515) and Ser(518) and was abolished in cells lacking AMPK catalytic subunits...
November 8, 2016: Science Signaling
https://www.readbyqxmd.com/read/27752371/myeloproliferative-neoplasm-or-reactive-process-a-rare-case-of-acute-myeloid-leukemia-and-transient-posttreatment-megakaryocytic-hyperplasia-with-jak-2-mutation
#11
Steven Wang, Jie Yan, Guangde Zhou, Rebecca Heintzelman, J Steve Hou
Myeloproliferative neoplasms (MPNs) are hematopoietic malignancies characterized by unchecked proliferation of differentiated myeloid cells. The most common BCR-ABL1-negative MPNs are polycythemia vera, essential thrombocythemia, and primary myelofibrosis. The discovery of JAK2 V617F mutation has improved our understanding of the molecular basis of MPN. The high frequency of JAK2 mutation in MPN makes JAK2 mutation testing an essential diagnostic tool and potential therapeutic target for MPN. Here, we present a rare case of a 34-year-old patient who was initially diagnosed with acute myeloid leukemia (AML) with mutated NPM1...
2016: Case Reports in Hematology
https://www.readbyqxmd.com/read/27729820/ruxolitinib-in-the-treatment-of-polycythemia-vera-patient-selection-and-special-considerations
#12
REVIEW
Sabine Blum, Filipe Martins, Lorenzo Alberio
The discovery of JAK2 V617F mutation in the mid-2000s started to fill the gap between clinical presentation of polycythemia vera (PV), first described by Vaquez at the end of the 19th century, and spontaneous erythroid colony formation, reported by Prchal and Axelrad in the mid-1970s. The knowledge on this mutation brought an important insight to our understanding of PV pathogenesis and led to a revision of the World Health Organization diagnostic criteria in 2008. JAK-STAT is a major signaling pathway implicated in survival and proliferation of hematopoietic precursors...
2016: Journal of Blood Medicine
https://www.readbyqxmd.com/read/27658882/peripheral-and-bone-marrow-cd34-cell-levels-on-chronic-myeloproliferative-disease
#13
M Pamukcuoglu, K Acar, B Celik, N Akyurek, M S Pepeler, G T Sucak
PURPOSE: The aim of the present study was to examine the relationship between peripheral CD34(+) and bone marrow CD34(+) levels and the clinicopathologic characteristics and laboratory parameters of myeloproliferative disease (MPD) patients. PATIENTS AND METHODS: A total of 103 MPD patients were enrolled in this study. We examined the relationship between bone marrow CD34(+) and peripheral CD34(+) levels and the patients' clinicopathologic and laboratory parameters...
September 22, 2016: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/27637012/prognostic-significance-of-p2ry8-crlf2-and-crlf2-overexpression-may-vary-across-risk-subgroups-of-childhood-b-cell-acute-lymphoblastic-leukemia
#14
Hu Dou, Xi Chen, Yi Huang, Yongchun Su, Ling Lu, Jie Yu, Yibing Yin, Liming Bao
The cytokine receptor-like factor 2 (CRLF2) gene plays an important role in early B-cell development. Aberrations in CRLF2 activate the JAK-STAT signaling pathway that contributes to B-cell acute lymphoblastic leukemia (B-ALL). The prognostic significance of CRLF2 overexpression and P2RY8-CRLF2 fusion in various B-ALL risk subgroups has not been well established. Two hundred seventy-one patients with newly diagnosed childhood B-ALL were enrolled from a Chinese population. The prevalence of CRLF2 overexpression, CRLF2-P2RY8 fusion, CRLF2 F232C mutation, and JAK2 and IL7R mutational status were analyzed, and the prognostic impact of CRLF2 overexpression and P2RY8-CRLF2 on B-ALL was evaluated by assessing their influence on overall survival and event-free survival...
February 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/27582015/circulating-cd34-cell-count-differentiates-primary-myelofibrosis-from-other-philadelphia-negative-myeloproliferative-neoplasms-a-pragmatic-study
#15
MULTICENTER STUDY
C Orvain, D Luque Paz, I Dobo, L Cottin, G Le Calvez, A Chauveau, M Mercier, J Farhi, F Boyer, J C Ianotto, B Guibourg, M C Rousselet, M Zandecki, N Ifrah, M Hunault-Berger, V Ugo, F Genevieve
A high number of circulating CD34+ cells has been advocated to distinguish primary myelofibrosis from other Philadelphia-negative myeloproliferative neoplasms. We re-evaluated the diagnostic interest of measuring circulating CD34+ cells in 26 healthy volunteers and 256 consecutive patients at diagnosis for whom a myeloproliferative neoplasm was suspected. The ROC curve analysis showed that a number of CD34+ <10/μl excludes the diagnosis of primary myelofibrosis with a sensitivity of 97 % and a specificity of 90 % (area under the curve: 0...
October 2016: Annals of Hematology
https://www.readbyqxmd.com/read/27570091/clinical-and-histological-characteristics-of-livedo-racemosa-in-essential-thrombocythemia-a-report-of-two-cases-and-review-of-the-published-works
#16
Sae Inoue, Naoko Okiyama, Mari Okune, Nagisa Shiraki, Reiko Kessoku, Manabu Fujimoto
Essential thrombocythemia (ET) is a rare clonal myeloproliferative disorder with a prevalence rate of approximately 1-3 cases per 100 000 individuals per year. ET is characterized by a persistent increase in the platelet count with hyperplasia of bone marrow megakaryocytes. It is difficult to make a diagnosis of ET, because most thrombocythemia are reactive to certain disease conditions including iron deficiency anemia, infection, collagen diseases and malignant tumors. Mutation in the Janus kinase (JAK)2 gene is present in approximately 50-70% of ET patients, and somatic mutations in the calreticulin (CALR) gene were recently discovered in approximately 20-25% of sporadic patients with ET or primary myelofibrosis...
August 29, 2016: Journal of Dermatology
https://www.readbyqxmd.com/read/27554814/efficacy-of-the-janus-kinase-1-2-inhibitor-ruxolitinib-in-the-treatment-of-vasculopathy-associated-with-tmem173-activating-mutations-in-3-children
#17
Marie-Louise Frémond, Mathieu Paul Rodero, Nadia Jeremiah, Alexandre Belot, Eric Jeziorski, Darragh Duffy, Didier Bessis, Guilhem Cros, Gillian I Rice, Bruno Charbit, Anne Hulin, Nihel Khoudour, Consuelo Modesto Caballero, Christine Bodemer, Monique Fabre, Laureline Berteloot, Muriel Le Bourgeois, Philippe Reix, Thierry Walzer, Despina Moshous, Stéphane Blanche, Alain Fischer, Brigitte Bader-Meunier, Fréderic Rieux-Laucat, Yanick Joseph Crow, Bénédicte Neven
No abstract text is available yet for this article.
December 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27531097/refractory-arterial-insufficiency-associated-with-janus-kinase-2-positive-essential-thrombocythaemia
#18
Yogeesan Sivakumaran, Anthony Freeman
Essential thrombocythaemia (ET) is one of the severe rare clonal haematologic stem cell disorders that encompass myeloproliferative neoplasms. ET has a well-described association with peripheral arterial thrombosis, which presents a challenging clinical presentation. Further understanding into the underlying pathophysiology of thrombosis in ET has been made following the identification of the Janus Kinase 2 (JAK2) mutation, which is thought to confer a prothrombotic phenotype. Here we present a case of refractory arterial insufficiency associated with JAK2-positive ET...
January 2017: Annals of Vascular Surgery
https://www.readbyqxmd.com/read/27473820/janus-kinase-jak-inhibitors-in-the-treatment-of-inflammatory-and-neoplastic-diseases
#19
REVIEW
Robert Roskoski
The Janus kinase (JAK) family of non-receptor protein-tyrosine kinases consists of JAK1, JAK2, JAK3, and TYK2 (tyrosine kinase-2). Each of these proteins contains a JAK homology pseudokinase (JH2) domain that regulates the adjacent protein kinase domain (JH1). JAK1/2 and TYK2 are ubiquitously expressed whereas JAK3 is found predominantly in hematopoietic cells. The Janus kinase family is regulated by numerous cytokines including interleukins, interferons, and hormones such as erythropoietin, thrombopoietin, and growth hormone...
September 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27468853/correlation-between-jak2-allele-burden-and-pulmonary-arterial-hypertension-and-hematological-parameters-in-philadelphia-negative-jak2-positive-myeloproliferative-neoplasms-an-egyptian-experience
#20
Mervat M Mattar, Mohammed Abdel Kader Morad, Noha M El Husseiny, Noha H Ali, Doaa M El Demerdash
Myeloproliferative neoplasms are characterized by a common stem cell-derived clonal proliferation, but are phenotypically diverse. JAK2 is mutated (V617F) in more than 90 % of patients with polycythemia vera (PV) and approximately 60 % of patients with essential thrombocythemia (ET) or primary myelofibrosis (PMF). Pulmonary arterial hypertension (PAH) is a major complication of several hematological disorders. Chronic myeloproliferative disorders associated with PAH have been included in group five for which the etiology is unclear and/or multifactorial...
October 2016: Annals of Hematology
keyword
keyword
75870
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"