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calreticulin mutation

Nariyoshi Matsumoto, Sayaka Mori, Hiroo Hasegawa, Daisuke Sasaki, Hayato Mori, Kazuto Tsuruda, Daisuke Imanishi, Yoshitaka Imaizumi, Tomoko Hata, Norihito Kaku, Kousuke Kosai, Naoki Uno, Yasushi Miyazaki, Katsunori Yanagihara
INTRODUCTION: Recently, novel calreticulin (CALR) mutations were discovered in Janus kinase 2 (JAK2) non-mutated myelofibrosis (PMF) and essential thrombocythemia (ET) cases, with a frequency of 60-80%. We examined clinical correlations and CALR mutation frequency in our myeloproliferative neoplasms (MPN) cases, and introduce an effective test method for use in clinical practice. METHODS: We examined 177 samples previously investigated for the JAK2 mutation for differential diagnosis of MPN...
November 1, 2016: Clinica Chimica Acta; International Journal of Clinical Chemistry
Uri Rozovski, Srdan Verstovsek, Taghi Manshouri, Vilma Dembitz, Ksenija Bozinovic, Kate Newberry, Ying Zhang, Joseph E Bove, Sherry Pierce, Hagop Kantarjian, Zeev Estrov
In most patients with primary myelofibrosis, one of three mutually exclusive somatic mutations is detected. In approximately 60% of patients, the Janus kinase 2 gene is mutated; in 20%, the calreticulin gene is mutated; and in 5%, the myeloproliferative leukemia virus gene is mutated. Although patients with mutated calreticulin or myeloproliferative leukemia have a favorable outcome and those with none of these mutations have an unfavorable outcome, prognostication based on mutation status is challenging owing to the heterogeneous survival of patients with mutated Janus kinase 2...
September 29, 2016: Haematologica
Laila Nomani, Juraj Bodo, Xiaoxian Zhao, Lisa Durkin, Sanam Loghavi, Eric D Hsi
OBJECTIVES: Mutations in CALR (calreticulin) have been discovered in 50% to 80% of JAK2 (Janus kinase 2) and MPL (myeloproliferative leukemia protein) wild-type patients with Philadelphia-negative myeloproliferative neoplasm (MPNs). We evaluate the performance of a monoclonal antibody for immunohistochemical detection of CALR mutations. METHODS: A computerized archival search was performed for cases of non-chronic myeloid leukemia (CML) MPNs with available CALR and JAK2 V617F mutational analysis data...
October 2016: American Journal of Clinical Pathology
Daria Sollazzo, Dorian Forte, Nicola Polverelli, Margherita Perricone, Marco Romano, Simona Luatti, Nicola Vianelli, Michele Cavo, Francesca Palandri, Lucia Catani
Myelofibrosis (MF) is a clonal neoplasia of the hemopoietic stem/progenitor cells associated with genetic mutations in the Janus kinase 2 (JAK2), myeloproliferative leukemia virus oncogene (MPL), and calreticulin (CALR) genes. MF is also characterized by a state of chronic inflammation. Calreticulin (CRT), as a multifunctional protein, is involved in a spectrum of cellular processes including inflammation, autoimmunity, and cancer initiation/progression. Based on this background, we hypothesised that in MF circulating CRT might reflect the inflammatory process...
2016: Mediators of Inflammation
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
Kathrin A Limberger, Lioudmila Bogatyreva, Rumyana Todorova, Bettina Herde, Dieter Hauschke, Heike L Pahl, Martin Werner, Konrad Aumann
Tissue microarray (TMA) technique is an established high-throughput method to analyze multiple tissue specimens in parallel. However, in order to obtain reliable results from immunohistochemical analyses of TMA blocks, cell composition of TMA spots must correspond to whole tissue sections (WTS) particularly in tissues with a heterogeneous cell composition as it is the case in myeloproliferative neoplasms (MPN). The aim of this study was to validate TMA of bone marrow biopsies from MPN patients. TMAs of MPN bone marrow biopsies (ET: n = 26, PV: n = 26, and PMF: n = 29) were compiled in triplicates and MPN-specific histological parameters were assessed...
August 20, 2016: Histochemistry and Cell Biology
H Y Yamada, G Kumar, Y Zhang, E Rubin, S Lightfoot, W Dai, C V Rao
Mitotic error-mediated chromosome instability (CIN) can lead to aneuploidy, chromothripsis, DNA damage and/or whole chromosome gain/loss. CIN may prompt rapid accumulation of mutations and genomic alterations. Thus, CIN can promote carcinogenesis. This CIN process results from a mutation in certain genes or environmental challenge such as smoking, and is highly prevalent in various cancers, including lung cancer. A better understanding of the effects of CIN on carcinogenesis will lead to novel methods for cancer prevention and treatment...
2016: Oncogenesis
Irina Panovska-Stavridis, Aleksandar Eftimov, Martin Ivanovski, Aleksandar Stojanovic, Borce Georgievski, Lidija Cevreska, Aleksandar J Dimovski
BACKGROUND: Acquired calreticulin (CALR) gene mutations are one of the molecular hallmarks of essential thrombocythemia (ET). It has been suggested that patients with ET with CALR mutations are associated with a distinct clinical phenotype. PATIENTS AND METHODS: We evaluated the clinical and molecular features of 150 patients with ET followed over a period of 15 years. The screening for the presence of insertion/deletion mutations in CALR exon 9 was done with a fluorescent polymerase chain reaction/capillary electrophoresis procedure...
August 2016: Clinical Lymphoma, Myeloma & Leukemia
Toshinori Kondo, Taizo Tasaka, Nanako Tomioka, Fuminori Sano, Hirotoshi Tokunaga, Shin-Ichiro Suemori, Takayuki Tsujioka, Yoshiko Matsuhashi, Hidekazu Nakanishi, Hideho Wada, Kaoru Tohyama, Takashi Sugihara
Calreticulin (CALR) and JAK2-V617F gene mutations, which are major genetic mutations in patients with primary myelofibrosis (PMF) and essential thrombocythemia (ET), exert different effects on the clinical features and outcomes of these diseases. We analyzed 88 and 9 patients with ET and PMF, respectively, and determined the differences in the clinical characteristics of ET patients with JAK2-V617F compared with CALR mutations. The frequency of the JAK2-V617F and CALR mutations were 64 and 22 %, respectively...
2016: SpringerPlus
Matthieu Mosca, Gaëlle Vertenoeil, Katte Rao Toppaldoddi, Isabelle Plo, William Vainchenker
BIOLOGICAL ASPECTS OF JAK/STAT SIGNALING IN BCR-ABL-NEGATIVE MYELOPROLIFERATIVE NEOPLASMS: Myeloproliferative disorders more recently named Myeloproliferative neoplasms (MPN) display several clinical entities: chronic myeloid leukemia (CML), the classical MPN including polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF) and atypical and unclassifiable NMP. The term MPN is mostly used for classical BCR-ABL-negative (myeloproliferative disorder) (ET, PV, PMF). These are clonal diseases resulting from the transformation of an hematopoietic stem cell and leading to an abnormal production of myeloid cells...
June 2016: Bulletin du Cancer
Kang Min-Gu, Choi Hyun-Woo, Lee Jun Hyung, Choi Yong Jun, Choi Hyun-Jung, Shin Jong-Hee, Suh Soon-Pal, Michael Szardenings, Kim Hye-Ran, Shin Myung-Geun
Janus kinase 2 (JAK2) and calreticulin (CALR) constitute the two most frequent mutations in essential thrombocythemia (ET), and both are reported to be mutually exclusive. Hence, we examined a cohort of 123 myeloproliferative neoplasm (MPN) patients without BCR-ABL1 rearrangement and additional ET patients (n=96) for coexistence of JAK2 and CALR mutations. The frequency of CALR mutations was 20.3% in 123 MPN patients; 31.1% in ET (n=74), 25% in primary myelofibrosis (n=4) and 2.2% in polycythemia vera (n=45)...
July 30, 2016: Oncotarget
Hao Kong, Yancheng Liu, Sai Luo, Qiaoqiao Li, Qinglu Wang
Objective As the calreticulin (CALR) mutation frequency is significantly associated with essential thrombocythemia (ET) and primary myelofibrosis (PMF), this mutation may be an important biomarker in patients with ET and PMF. Methods We performed a literature search until April 2015 and obtained 21 relevant studies. The outcome was pooled as the effect size by using the Stata software program. Results The CALR mutation frequencies in patients with ET and PMF were 19% and 22%, respectively. The CALR mutation ratio in Asian patients with ET was 23% and higher than that in European-American patients (16%)...
2016: Internal Medicine
Natasha Szuber, Bruno Lamontagne, Lambert Busque
Mutations in the calreticulin (CALR) gene are found in the majority of Janus kinase 2-negative myeloproliferative neoplasms MPN and, thus far, have exclusively been reported as acquired, somatic mutations. We assessed the mutational status of exon 9 of the CALR gene in 2000 blood samples submitted to our centre and identified 12 subjects (0.6%) harbouring distinctive CALR mutations, all with an allelic frequency of 50% and all involving indels occurring as multiples of 3 bp. Buccal cell samples obtained from these patients confirmed the germline nature of the mutations...
July 27, 2016: Journal of Clinical Pathology
Chao Sun, Xin Zhou, Zhi-Jian Zou, Hong-Feng Guo, Jian-Yong Li, Chun Qiao
BACKGROUND: Recently, calreticulin (CALR) gene mutations have been identified in patients with essential thrombocythemia (ET). A high-frequency of ET cases without Janus kinase 2 (JAK2) mutations contain CALR mutations and exhibit clinical characteristics different from those with mutant JAK2. Thus, we investigated the frequency and clinical features of Chinese patients of Han ethnicity with CALR mutations in ET. METHODS: We recruited 310 Chinese patients of Han ethnicity with ET to analyze states of CALR, JAK2V617F, and MPLW515 mutations by polymerase chain reaction and direct sequencing...
August 5, 2016: Chinese Medical Journal
Thomas Jaeger, Axel Muendlein, Jasmin Hodaie, Gerold Untergasser, Michael Steurer, Christoph H Saely, Heinz Drexel, Alois H Lang
INTRODUCTION: Acquired JAK2 as well as calreticulin (CALR) mutations are involved in the development of Philadelphia-negative myeloproliferative neoplasms (MPN). We previously showed that the JAK2 V617F mutation could also been found in coronary patients and in patients with peripheral arterial disease (PAD). However, prevalence of CALR mutations is unknown in vascular risk patients and its evaluation subject of the present study. MATERIALS AND METHODS: We determined the prevalence of CALR exon 9 indel mutations in a cohort of 1052 angiographied coronary patients, including 141 patients with PAD, and, additionally, 86 patients with PAD, but without coronary angiography...
August 2016: Thrombosis Research
Ronnie Lum, Samar Ahmad, Seo Jung Hong, Daniel C Chapman, Guennadi Kozlov, David B Williams
Calreticulin is a lectin chaperone of the endoplasmic reticulum that interacts with newly synthesized glycoproteins by binding to Glc1Man9GlcNAc2 oligosaccharides as well as to the polypeptide chain. In vitro, the latter interaction potently suppresses the aggregation of various non-glycosylated proteins. Although the lectin-oligosaccharide association is well understood, the polypeptide-based interaction is more controversial because the binding site on calreticulin has not been identified, and its significance in the biogenesis of glycoproteins in cells remains unknown...
September 9, 2016: Journal of Biological Chemistry
Munazza Rashid, Rifat Zubair Ahmed, Shariq Ahmed, Muhammad Nadeem, Nuzhat Ahmed, Tahir Sultan Shamsi
Classic "BCR-ABL1-negative" MPN is an operational sub-category of MPN that includes polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) harboring JAK2V617F as the most common mutation. JAK2V617F can be detected in about 95 % of patients with PV while remaining 5 % of PV patients carry a somatic mutation of JAK2 exon 12. Approximately one-third of patients with ET or PMF do not carry any mutation in JAK2 or MPL. In December 2013, mutations were described in calreticulin (CALR) gene in 67-71 and 56-88 % of JAK2V617F and MPL negative patients with ET and PMF, respectively...
June 2016: Indian Journal of Hematology & Blood Transfusion
Cristina Bilbao-Sieyro, Yanira Florido, María Teresa Gómez-Casares
Identification of somatic frameshift mutations in exon 9 of the calreticulin gene (CALR) in myeloproliferative neoplasms (MPNs) in December of 2013 has been a remarkable finding. It has provided a new molecular diagnostic marker, particularly in essential thrombocythemia (ET) and primary myelofibrosis (PMF), where is the second most common altered gene after JAK2V617F. There are two main types of CALR mutants, type 1 and type 2, and there is evidence about their distinct clinical/prognostic implications, for instances, it is believed that favorable outcome might be restricted to type-1 in PMF...
July 1, 2016: Oncotarget
Archana Agarwal, Kerry Morrone, Matthias Bartenstein, Zhizhuang Joe Zhao, Amit Verma, Swati Goel
Primary myelofibrosis (PMF) is a Philadelphia chromosome negative myeloproliferative neoplasm (MPN) with adverse prognosis and is associated with bone marrow fibrosis and extramedullary hematopoiesis. Even though the discovery of the Janus kinase 2 (JAK2), thrombopoietin receptor (MPL) and calreticulin (CALR) mutations have brought new insights into the complex pathogenesis of MPNs, the etiology of fibrosis is not well understood. Furthermore, since JAK2 inhibitors do not lead to reversal of fibrosis further understanding of the biology of fibrotic process is needed for future therapeutic discovery...
2016: Stem Cell Investigation
Aoibhinn Clinton, Mary Frances McMullin
The Philadelphia negative myeloproliferative neoplasms include polycythaemia vera (PV), essential thrombocytopenia (ET) and primary myelofibrosis (PMF). Patients with these conditions were mainly thought to harbour JAK2V617F mutations or an Myeloproliferative leukaemia (MPL) substitution. In 2013, two revolutionary studies identified recurrent mutations in a gene that encodes the protein calreticulin (CALR). This mutation was detected in patients with PMF and ET with non-mutated JAK2 or MPL but was absent in patients with PV...
October 2016: Journal of Clinical Pathology
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