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myeloproliferative chronic neoplasm

Zhen-Ling Li, Li Gao, Hui Zhang, Chun-Xia Zhang, Yan-Rong Chen, Fan-Zhou Huang, Ming Gong, Ya-Yue Gao, Yin Tang, Yi-Gai Ma
OBJECTIVE: To detect the JAK2, CALR and MPL gene mutations in patients with BCR/ABL1 negative chronic myeloproliferative diseases(BCR/ABL1-CMPD)and to evaluate their diagnostic value. METHODS: Two hundred and eight cases of BCR/ABL1-CMPD comprising of 146 cases of essential thrombocythemia(ET), 37 cases of polycythemia vera(PV)and 25 cases of primary myelofibrosis(PMF)from March 2012 to December 2015 were enrolled in the BCR/ABL1-CMPD, while 124 cases of secondary thrombocythemia and 73 cases of secondary polycythemia were enrolled in the control group...
August 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
Lauren C Schwartz, John Mascarenhas
Atypical chronic myeloid leukemia (aCML) is a BCR-ABL1 negative myelodysplastic (MDS)/myeloproliferative (MPN) neoplasm with poor overall survival. The current 2016 WHO classification of myeloid neoplasms allows clinicians to more accurately differentiate aCML from its similar MDS/MPN overlap and MPN counterparts. In addition, the advent of next-generation sequencing has expanded our understanding of the molecular pathogenesis of aCML and its therapeutic potential. Hematopoietic stem cell transplant (HSCT) remains the first consideration in the treatment algorithm for aCML, however, with the advances in mutational analysis, opportunities for targeted therapy have expanded...
July 29, 2018: Blood Reviews
Camilla de S Borges, Aline F Ferreira, Vitor H Almeida, Fausto G Gomes, Maria Gabriela Berzoti-Coelho, Maira da Costa Cacemiro, Natalia S Nunes, Lorena L Figueiredo-Pontes, Belinda P Simões, Fabíola A Castro, Robson Q Monteiro
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by the presence of the Philadelphia chromosome, which generates the oncogene BCR-ABL1. Protease-activated receptor 1 (PAR1) is involved in tumor progression and angiogenesis. We have previously reported that PAR1 expression is elevated in human leukemias that display a more aggressive clinical behavior, including the blast crisis of CML. In this study, we analyzed the crosstalk between the oncoprotein BCR-ABL and PAR1 in CML. Leukemic cell lines transfected with the BCR-ABL1 oncogene showed significantly higher expression levels of PAR1 compared to that of wild-type counterparts...
August 1, 2018: Experimental Hematology
Subhayan Chattopadhyay, Guoqiao Zheng, Amit Sud, Hongyao Yu, Kristina Sundquist, Jan Sundquist, Asta Försti, Akseli Hemminki, Richard Houlston, Kari Hemminki
BACKGROUND: Although advances in the treatment of myeloid neoplasms have led to improved patient survival, this improvement has been accompanied by an increased risk of second primary cancer (ie, the risk of another cancer after myeloid neoplasia). We aimed to assess bi-directional associations between myeloid cancers and other cancers-ie, development of second primary cancer in patients who have previously had myeloid cancer, and risks of myeloid neoplasia in patients who have previously had another cancer-to provide insight into possible mechanisms beyond side-effects of treatment and shared risk factors...
August 2018: Lancet Haematology
Tariq I Mughal, Thomas Lion, Omar Abdel-Wahab, Ruben Mesa, Robyn M Scherber, Danilo Perrotti, Michael Mauro, Srdan Verstovsek, Giuseppe Saglio, Richard A Van Etten, Robert Kralovics
Following the 47th American Society of Hematology Meeting in 2005, the late John Goldman and Tariq Mughal commenced a conference, the 1st Post-ASH Workshop, which brought together clinicians and scientists, to accelerate the adoption of new therapies for patients with myeloproliferative neoplasms (MPNs). The concept began with recognition of the CML success story following imatinib therapy, the discovery of JAK2V617F , and the demonstration that BCR-ABL1-negative MPNs are driven by abnormal JAK2 activation...
August 3, 2018: Hematological Oncology
Yelena Z Ginzburg, Maria Feola, Eran Zimran, Judit Varkonyi, Tomas Ganz, Ronald Hoffman
Polycythemia vera (PV) is a chronic myeloproliferative neoplasm. Virtually all PV patients are iron deficient at presentation and/or during the course of their disease. The co-existence of iron deficiency and polycythemia presents a physiological disconnect. Hepcidin, the master regulator of iron metabolism, is regulated by circulating iron levels, erythroblast secretion of erythroferrone, and inflammation. Both decreased circulating iron and increased erythroferrone levels, which occur as a consequence of erythroid hyperplasia in PV, are anticipated to suppress hepcidin and enable recovery from iron deficiency...
July 24, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Peter Valent, Emir Hadzijusufovic, Thomas Grunt, Heidrun Karlic, Barbara Peter, Harald Herrmann, Gregor Eisenwort, Gregor Hoermann, Axel Schulenburg, Michael Willmann, Rainer Hubmann, Medhat Shehata, Edgar Selzer, Karoline V Gleixner, Thomas Rülicke, Wolfgang R Sperr, Brigitte Marian, Michael Pfeilstöcker, Hubert Pehamberger, Felix Keil, Ulrich Jäger, Christoph Zielinski
In 2008 the Ludwig Boltzmann Cluster Oncology (LBC ONC) was established on the basis of two previous Ludwig Boltzmann Institutes working in the field of hematology and cancer research. The general aim of the LBC ONC is to improve treatment of hematopoietic neoplasms by eradicating cancer-initiating and disease-propagating cells, also known as leukemic stem cells (LSC) in the context of leukemia. In a first phase, the LBC ONC characterized the phenotype and molecular aberration profiles of LSC in various malignancies...
July 13, 2018: Wiener Klinische Wochenschrift
Kanwaljeet Singh, Sudha Sazawal, Sunita Chhikara, Manoranjan Mahapatra, Renu Saxena
Background: : It is still a matter of debate regarding the association of JAK2V617F mutation with thrombosis in BCR-ABL negative CMPN patients. The role of JAK2V617F mutation in increasing the thrombotic risk in CMPNs is yet unequivocal. Aims: : To clarify the contribution of JAK2V617F mutation in thrombosis in CMPN patients. Settings and Design: This retrospective study was done to evaluate role of JAK2V617F mutation in thrombosis in CMPNs...
July 2018: Indian Journal of Pathology & Microbiology
Morten Orebo Holmström, Hans Carl Hasselbalch
The myelodysplastic syndromes, the chronic myeloproliferative neoplasms, and the acute myeloid leukemia are malignancies of the myeloid hematopoietic stem cells of the bone marrow. The diseases are characterized by a dysregulation of the immune system as both the cytokine milieu, immune phenotype, immune regulation, and expression of genes related to immune cell functions are deregulated. Several treatment strategies try to circumvent this deregulation, and several clinical and preclinical trials have shown promising results, albeit not in the same scale as chimeric antigen receptor T cells have had in the treatment of refractory lymphoid malignancies...
July 9, 2018: Seminars in Immunopathology
Prajwal Boddu, Dai Chihara, Lucia Masarova, Naveen Pemmaraju, Keyur P Patel, Srdan Verstovsek
Myeloproliferative neoplasms (MPNs) are clonal disorders characterized by proliferation of one or more elements of the myeloid lineage. Key genetic aberrations include the BCR-ABL1 gene rearrangement in Philadelphia chromosome-positive chronic myelogenous leukemia (CML) and JAK2/MPL/CALR aberrations in Philadelphia chromosome-negative MPNs. While thought to be mutually exclusive, occasional isolated reports of coexistence of BCR-ABL1 and JAK2, and JAK2 with MPL or CALR aberrations have been described. Given the paucity of data, clinical characteristics and outcome of patients harboring concurrent Philadelphia-positive and Philadelphia-negative mutations or dual Philadelphia-negative driver mutations have not been systematically evaluated, and their clinical relevance is largely unknown...
June 27, 2018: Annals of Hematology
Marijana Kovačić, Olivera Mitrović-Ajtić, Bojana Beleslin-Čokić, Dragoslava Djikić, Tijana Subotički, Miloš Diklić, Danijela Leković, Mirjana Gotić, Pascal Mossuz, Vladan P Čokić
PURPOSE: Previously, the family of S100A proteins has been found to be associated with inflammation and myelopoiesis and to be able to induce or support myeloproliferation during chronic inflammation. Here, we studied the inflammatory myeloid-related proteins S100A4, S100A8, S100A9 and S100A12 in myeloproliferative neoplasms (MPNs) in order to assess the involvement of chronic inflammation in the pathogenesis of MPN. METHODS: We analyzed the S100A4, S100A8, S100A9 and S100A12 mRNA and protein levels in the bone marrow and circulation of 140 patients with MPN and 15 healthy controls using Western blotting, microarray-based mRNA expression profiling and ELISA assays, respectively...
June 26, 2018: Cellular Oncology (Dordrecht)
Oriol Plans Galván, Hipólito Pérez Moltó, Ariadna Fabià-Mayans, Blanca Xicoy, José Luis Mate, Pilar Ricart Martí
Hydroxyurea (HU) is a drug frequently used in the treatment of chronic myeloproliferative neoplasms. The most common side effects of this drug are pancytopenia, digestive and skin disorders. Respiratory complications are rare and there are less than 20 cases described, only 5 of which underwent an anatomopathological study. We present the case of a patient with chronic myeloproliferative neoplasm who developed interstitial pneumonitis probably due to HU according to histological study.
2018: Clinical Medicine Insights. Case Reports
Mrinal M Patnaik, Ayalew Tefferi
DISEASE OVERVIEW: Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell disorder with overlapping features of myelodysplastic syndromes and myeloproliferative neoplasms, with an inherent risk for leukemic transformation (∼15%-20% over 3-5 years). DIAGNOSIS: Diagnosis is based on the presence of sustained (>3 months) peripheral blood monocytosis (≥1 × 109 /L; monocytes ≥10%), along with bone marrow dysplasia. Clonal cytogenetic abnormalities occur in ∼ 30% of patients, while >90% have gene mutations...
June 2018: American Journal of Hematology
Morten Orebo Holmström, Caroline Hasselbalch Riley, Vibe Skov, Inge Marie Svane, Hans Carl Hasselbalch, Mads Hald Andersen
The Chronic Myeloproliferative Neoplasms (MPN) are cancers characterized by hyperinflammation and immune deregulation. Concurrently, the expression of the immune check point programmed death ligand 1 (PD-L1) is induced by inflammation. In this study we report on the occurrence of spontaneous T cell responses against a PD-L1 derived epitope in patients with MPN. We show that 71% of patients display a significant immune response against PD-L1, and patients with advanced MPN have significantly fewer and weaker PD-L1 specific immune responses compared to patients with non-advanced MPN...
2018: Oncoimmunology
Zachary G Jacobs, Bongani Kaimila, Peter M Wasswa, Thuy Bui
No abstract text is available yet for this article.
March 2018: Malawi Medical Journal: the Journal of Medical Association of Malawi
Magalie Haissaguerre, Amandine Ferriere, Samantha Clark, Omar Guzman-Quevedo, Antoine Tabarin, Daniela Cota
The pathophysiology of body weight gain that is observed in patients suffering from myeloproliferative neoplasms treated with inhibitors of the janus kinase (Jak) 1 and 2 pathway remains unknown. Here we hypothesized that this class of drugs interferes with the metabolic actions of leptin, as this hormone requires functional Jak2 signaling. To test this, C57BL/6J chow-fed mice received either chronic intraperitoneal (ip) or repeated intracerebroventricular (icv) administration of the selective Jak2 inhibitor NVP-BSK805, which was proven efficacious in treating polycythemia in rodents...
2018: Frontiers in Pharmacology
Filipa Mousinho, Ana P Azevedo, Tatiana Mendes, Paula Sousa E Santos, Rita Cerqueira, Sónia Matos, Sónia Santos, Sância Ramos, João Faro Viana, Fernando Lima
Myeloproliferative neoplasms (MPNs) are classically divided into BCR RhoGEF and GTPase activating protein (BCR)-ABL proto‑oncogene 1 non‑receptor tyrosine kinase (ABL) positive chronic myeloid leukemia (CML) and BCR‑ABL negative MPNs, including essential thrombocythemia (ET). One of the major diagnostic criteria for ET is the absence of the philadelphia chromosome, thus when present it is almost indicative of CML. ET and CML are considered to be mutually exclusive; however, there are rare situations in which patients with ET present positive BCR‑ABL without the features of CML...
July 2018: Molecular Medicine Reports
Yu Chen, Tongtong Wang, Jing Du, Yanchun Li, Xin Wang, Yi Zhou, XingXing Yu, Weimin Fan, Qiaojuan Zhu, Xiangmin Tong, Ying Wang
BACKGROUND/AIMS: Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm. Tyrosine kinase inhibitors (TKIs) are commonly used to treat CML; however, drug resistance of CML cells to TKIs has limited their clinical application. Shikonin, a traditional Chinese herb, has long been used to treat leukemia in China, but the roles and related molecular mechanisms of shikonin treatment in CML remain unclear. Here, we aimed to evaluate the effects of shikonin on the proliferation, apoptosis, and migration of K562 cells, a CML cell line...
2018: Cellular Physiology and Biochemistry
Yeonsook Moon, Mi Hyang Kim, Hye Ryoun Kim, Jeong Yeal Ahn, Jungwon Huh, Ji Young Huh, Jae Ho Han, Joon Seong Park, Sung Ran Cho
The 2016 WHO diagnostic criteria for chronic myelomonocytic leukemia (CMML) require both absolute and relative monocytosis (≥1×10⁹/L and ≥10% of white blood cell counts) in peripheral blood. Moreover, myeloproliferative neoplasm (MPN) features in bone marrow and/or MPN-associated mutations tend to support MPN with monocytosis rather than CMML. We assessed the impact of the 2016 WHO criteria on CMML diagnosis, compared with the 2008 WHO criteria, through a retrospective review of the medical records of 38 CMML patients diagnosed according to the 2008 WHO classification...
September 2018: Annals of Laboratory Medicine
Margherita Maffioli, Ester Orlandi, Francesco Passamonti
This review focuses on the management of elderly patients with chronic myeloid leukemia and chronic myeloproliferative neoplasms, including polycythemia vera, essential thrombocythemia and primary myelofibrosis. Median age in these neoplasms is within the 6th decades of age. All new therapies can be done at any age without absolute contraindication. However, the selection of the precise therapy for the single patient is mandatory. For these reasons, an accurate definition of diagnosis and prognostication is necessary...
May 22, 2018: European Journal of Internal Medicine
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