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myeloprolifeative neoplasm

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https://www.readbyqxmd.com/read/29455651/targeting-few-to-help-hundreds-jak-mapk-and-rock-pathways-as-druggable-targets-in-atypical-chronic-myeloid-leukemia
#1
REVIEW
Stefania Rocca, Giovanna Carrà, Pietro Poggio, Alessandro Morotti, Mara Brancaccio
Atypical Chronic Myeloid Leukemia (aCML) is a myeloproliferative neoplasm characterized by neutrophilic leukocytosis and dysgranulopoiesis. From a genetic point of view, aCML shows a heterogeneous mutational landscape with mutations affecting signal transduction proteins but also broad genetic modifiers and chromatin remodelers, making difficult to understand the molecular mechanisms causing the onset of the disease. The JAK-STAT, MAPK and ROCK pathways are known to be responsible for myeloproliferation in physiological conditions and to be aberrantly activated in myeloproliferative diseases...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29454474/cardiovascular-pulmonary-and-metabolic-toxicities-complicating-tyrosine-kinase-inhibitor-therapy-in-chronic-myeloid-leukemia-strategies-for-monitoring-detecting-and-managing
#2
REVIEW
Bruno C Medeiros, Jennifer Possick, Michael Fradley
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm, the incidence of which increases with age. Tyrosine kinase inhibitors (TKIs) are the mainstay of CML treatment, including imatinib, nilotinib, dasatinib, bosutinib, and ponatinib. Beyond matching patient disease profiles with TKI specificity, differences in the efficacy and toxicity profiles and a patient's comorbid risk factors should be considered when selecting the most appropriate agent. Our objectives are to review the incidence and severity of cardiovascular, metabolic, and pulmonary disorders associated with these TKIs, highlighting differences in adverse event profiles, suggested risk-mitigation strategies, and guidance for TKI selection in different settings...
February 3, 2018: Blood Reviews
https://www.readbyqxmd.com/read/29440636/chronic-neutrophilic-leukemia-new-science-and-new-diagnostic-criteria
#3
REVIEW
Natasha Szuber, Ayalew Tefferi
Chronic neutrophilic leukemia (CNL) is a distinct myeloproliferative neoplasm defined by persistent, predominantly mature neutrophil proliferation, marrow granulocyte hyperplasia, and frequent splenomegaly. The seminal discovery of oncogenic driver mutations in CSF3R in the majority of patients with CNL in 2013 generated a new scientific framework for this disease as it deepened our understanding of its molecular pathogenesis, provided a biomarker for diagnosis, and rationalized management using novel targeted therapies...
February 13, 2018: Blood Cancer Journal
https://www.readbyqxmd.com/read/29427461/thromboembolism-prophylaxis-in-patients-with-philadelphia-negative-myeloproliferative-neoplasms-clinical-practice-among-nordic-specialists
#4
O W Bjerrum, J Samuelsson, W Ghanima, M Kauppila, C L Andersen
BACKGROUND: Patients with Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) have higher risks of developing thromboembolisms compared to the general population. International guidelines on the management of MPNs therefore include recommendations concerning thromboembolism prophylaxis. In clinical practice strict adherence to guidelines may be challenging and dependent on factors such as physician experience, outpatient clinic setting and access to therapy, however, no data exist on physician adherence or patient compliance to thromboembolism prophylaxis in MPNs...
February 10, 2018: European Journal of Haematology
https://www.readbyqxmd.com/read/29427319/distinguishing-myelofibrosis-from-polycythemia-vera-and-essential-thrombocythemia-the-utility-of-enumerating-circulating-stem-cells-with-aberrant-hmicl-expression-by-flow-cytometry
#5
L L Herborg, L Nederby, H C Hasselbalch, A Aggerholm, A S Roug
INTRODUCTION: Diagnosing BCR-ABL negative myeloproliferative neoplasms (MPN) may be challenging due to overlapping features and lack of robust discriminatory parameters, especially between essential thrombocythemia (ET) and prefibrotic myelofibrosis (MF). Circulating immature hematopoietic cells are variably present in polycythemia vera (PV), ET, and MF. The C-type lectin hMICL is aberrantly expressed on hematopoietic stem cells in the majority of acute myeloid leukemia patients. However, the hMICL expression in MPN, having varying propensity of leukemic transformation, is unsettled...
February 10, 2018: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/29426921/the-2016-who-classification-and-diagnostic-criteria-for-myeloproliferative-neoplasms-document-summary-and-in-depth-discussion
#6
REVIEW
Tiziano Barbui, Jürgen Thiele, Heinz Gisslinger, Hans Michael Kvasnicka, Alessandro M Vannucchi, Paola Guglielmelli, Attilio Orazi, Ayalew Tefferi
The new edition of the 2016 World Health Organization (WHO) classification system for tumors of the hematopoietic and lymphoid tissues was published in September 2017. Under the category of myeloproliferative neoplasms (MPNs), the revised document includes seven subcategories: chronic myeloid leukemia, chronic neutrophilic leukemia, polycythemia vera (PV), primary myelofibrosis (PMF), essential thrombocythemia (ET), chronic eosinophilic leukemia-not otherwise specified and MPN, unclassifiable (MPN-U); of note, mastocytosis is no longer classified under the MPN category...
February 9, 2018: Blood Cancer Journal
https://www.readbyqxmd.com/read/29423961/pruritic-arthropod-bite-like-papules-in-t-cell-large-granular-lymphocytic-leukaemia-and-chronic-myelomonocytic-leukaemia
#7
D J Lewis, R N Miranda, C W Oh, T Hinojosa, L J Medeiros, J L Curry, M T Tetzlaff, C A Torres-Cabala, P Nagarajan, F Ravandi-Kashani, M Duvic
T-cell large granular lymphocytic leukaemia (T-LGLL) is a clinically indolent mature T-cell neoplasm characterized by a monoclonal population of CD3+ CD8+ cytotoxic T cells, which usually presents as neutropenia, anaemia and thrombocytopenia. Chronic myelomonocytic leukaemia (CMML) is a clonal haematopoietic disorder with features of both a myeloproliferative neoplasm and myelodysplastic syndrome (MDS). Patients with CMML exhibit a persistent peripheral blood monocytosis in addition to myelodysplastic features...
February 9, 2018: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/29417354/clonal-dynamics-in-a-case-of-acute-monoblastic-leukemia-that-later-developed-myeloproliferative-neoplasm
#8
Shinya Sato, Hidehiro Itonaga, Masataka Taguchi, Yasushi Sawayama, Daisuke Imanishi, Hideki Tsushima, Tomoko Hata, Yukiyoshi Moriuchi, Hiroyuki Mishima, Akira Kinoshita, Koh-Ichiro Yoshiura, Yasushi Miyazaki
In acute myeloid leukemia (AML), patients may harbor pre-leukemic hematopoietic stem cells (HSCs) containing some, but not all, of the mutations observed in the leukemic cells. These pre-leukemic HSCs may survive induction chemotherapy and contribute to AML relapse by obtaining additional mutations. We report here an acute monoblastic leukemia (AMoL) patient who later developed an unclassifiable myeloproliferative neoplasm (MPN-U). Whole-exome sequencing and cluster analysis demonstrated the presence of three distinct major clones during the clinical course: (1) an AMoL clone with ASXL1, CBL, and NPM1 somatic mutations, likely associated with the pathogenesis, and GATA2, SRSF2, and TET2 mutations, (2) an AMoL remission clone, with mutated GATA2, SRSF2, and TET2 only (possibly the founding clone (pre-leukemic HSC) that survived chemotherapy), (3) a small subclone which had JAK2 mutation during the AMoL remission, appearing at MPN-U manifestation with additional mutations...
February 7, 2018: International Journal of Hematology
https://www.readbyqxmd.com/read/29415577/jak-inhibition-and-symptom-control-in-myeloproliferative-neoplasms
#9
Prithviraj Bose, Mahesh Swaminathan
No abstract text is available yet for this article.
February 8, 2018: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/29411417/chronic-myeloid-leukemia-2018-update-on-diagnosis-therapy-and-monitoring
#10
Elias Jabbour, Hagop Kantarjian
DISEASE OVERVIEW: Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm with an incidence of 1-2 cases per 100 000 adults. It accounts for approximately 15% of newly diagnosed cases of leukemia in adults. DIAGNOSIS: CML is characterized by a balanced genetic translocation, t(9;22)(q34;q11.2), involving a fusion of the Abelson gene (ABL1) from chromosome 9q34 with the breakpoint cluster region (BCR) gene on chromosome 22q11.2. This rearrangement is known as the Philadelphia chromosome...
March 2018: American Journal of Hematology
https://www.readbyqxmd.com/read/29411299/a-rare-calr-variant-mutation-and-a-review-of-calr-in-essential-thrombocythemia
#11
Robert Diep, Ara Metjian
Essential thrombocythemia (ET) is an indolent myeloproliferative neoplasm characterized by megakaryocyte hyperplasia, thrombocytosis, thrombotic and hemorrhagic complications, and potential transformation into myelofibrosis and acute myeloid leukemia. The vast majority of cases are driven by a somatic mutation in JAK2, CALR, or MPL. CALR, a gene that codes for the calcium-binding chaperone calreticulin, is the predominant mutation in patients with non-mutated JAK2 essential thrombocythemia, accounting for 20-25% of the overall somatic mutation frequency in ET...
February 6, 2018: Journal of Thrombosis and Thrombolysis
https://www.readbyqxmd.com/read/29405428/the-2014-bcsh-criteria-and-the-2016-who-criteria-for-essential-thrombocythemia-a-comparison-in-a-large-scale-cohort
#12
Tomonori Ochiai, Hajime Yasuda, Marito Araki, Kyohei Misawa, Soji Morishita, Mai Nudejima, Yumi Hironaka, Shuichi Shirane, Yoko Edahiro, Akihiko Gotoh, Akimichi Ohsaka, Norio Komatsu
OBJECTIVE: There are currently two representative diagnostic criteria for essential thrombocythemia (ET), the 2014 British Committee for Standards in Hematology Guidelines (BCSH) criteria and the 2016 World Health Organization (WHO) criteria. We compare and discuss the advantages and disadvantages of the two criteria. METHOD: We applied the two criteria to 403 patients with thrombocytosis and suspected myeloproliferative neoplasms (MPN) and compared patient populations...
February 5, 2018: European Journal of Haematology
https://www.readbyqxmd.com/read/29405201/targeting-the-il-6-jak-stat3-signalling-axis-in-cancer
#13
REVIEW
Daniel E Johnson, Rachel A O'Keefe, Jennifer R Grandis
The IL-6/JAK/STAT3 pathway is aberrantly hyperactivated in many types of cancer, and such hyperactivation is generally associated with a poor clinical prognosis. In the tumour microenvironment, IL-6/JAK/STAT3 signalling acts to drive the proliferation, survival, invasiveness, and metastasis of tumour cells, while strongly suppressing the antitumour immune response. Thus, treatments that target the IL-6/JAK/STAT3 pathway in patients with cancer are poised to provide therapeutic benefit by directly inhibiting tumour cell growth and by stimulating antitumour immunity...
February 6, 2018: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/29404876/thrombosis-in-philadelphia-negative-classical-myeloproliferative-neoplasms-a-narrative-review-on-epidemiology-risk-assessment-and-pathophysiologic-mechanisms
#14
REVIEW
Somedeb Ball, Kyaw Zin Thein, Abhishek Maiti, Kenneth Nugent
Thrombosis is common in cancer patients and is associated with increased morbidity and mortality. Myeloproliferative neoplasms (MPN) are common malignancies in elderly individuals and are known for a high incidence of thrombotic complications. Different risk factors have been identified in studies, and risk models have been developed to identify patients with MPN at higher risk for thrombosis. Several pathophysiological mechanisms help explain the increased likelihood of thrombosis in these patients. Factors, such as leukocyte and platelet activation leading to the formation of leukocyte-platelet aggregates, activation of the coagulation cascade by microparticles, high levels of inflammatory cytokines, and endothelial dysfunction have a crucial role in thrombosis in MPN patients...
February 6, 2018: Journal of Thrombosis and Thrombolysis
https://www.readbyqxmd.com/read/29400094/gata1-insufficiencies-in-primary-myelofibrosis-and-other-hematopoietic-disorders-consequences-for-therapy
#15
Te Ling, John D Crispino, Maria Zingariello, Fabrizio Martelli, Anna Rita Migliaccio
GATA1, the founding member of a family of transcription factors, plays important roles in the development of hematopoietic cells of several lineages. Although loss of GATA1 has been known to impair hematopoiesis in animal models for nearly 25 years, the link between GATA1 defects and human blood diseases has only recently been realized. Areas covered: Here the current understanding of the functions of GATA1 in normal hematopoiesis and how it is altered in disease is reviewed. GATA1 is indispensable mainly for erythroid and megakaryocyte differentiation...
February 5, 2018: Expert Review of Hematology
https://www.readbyqxmd.com/read/29399328/jak-inhibitors-for-the-treatment-of-myeloproliferative-neoplasms-and-other-disorders
#16
REVIEW
William Vainchenker, Emilie Leroy, Laure Gilles, Caroline Marty, Isabelle Plo, Stefan N Constantinescu
JAK inhibitors have been developed following the discovery of the JAK2 V617F in 2005 as the driver mutation of the majority of non- BCR-ABL1 myeloproliferative neoplasms (MPNs). Subsequently, the search for JAK2 inhibitors continued with the discovery that the other driver mutations ( CALR and MPL ) also exhibited persistent JAK2 activation. Several type I ATP-competitive JAK inhibitors with different specificities were assessed in clinical trials and exhibited minimal hematologic toxicity. Interestingly, these JAK inhibitors display potent anti-inflammatory activity...
2018: F1000Research
https://www.readbyqxmd.com/read/29397860/-advances-in-pathogenesis-of-essential-thrombocythemia-review
#17
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
https://www.readbyqxmd.com/read/29387948/expression-of-hippo-signaling-pathway-and-aurora-kinase-genes-in-chronic-myeloid-leukemia
#18
Ana Paula Zambuzi Cardoso Marsola, Belinda Pinto Simões, Leonardo Carvalho Palma, Maria Gabriela Berzoti-Coelho, Sandra Mara Burin, Fabíola Attié de Castro
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm resulting from clonal expansion of hematopoietic stem cells positive for the Philadelphia chromosome. The CML pathogenesis is associated with expression of the BCR-ABL1 oncogene, which encodes the Bcr-Abl protein with tyrosine kinase activity, promoting the leukemic cell exacerbated myeloproliferation and resistance to apoptosis. CML patients are usually treated with tyrosine kinase inhibitors (TKI), but some of them acquire resistance or are refractory to TKI...
January 31, 2018: Medical Oncology
https://www.readbyqxmd.com/read/29378725/variability-of-pd-l1-expression-in-mastocytosis
#19
Ellen W Hatch, Mary Beth Geeze, Cheyenne Martin, Mohamed E Salama, Karin Hartmann, Gregor Eisenwort, Katharina Blatt, Peter Valent, Jason Gotlib, Ji-Hyun Lee, Lu Chen, Heather H Ward, Diane S Lidke, Tracy I George
Mastocytosis is a rare disease with heterogeneous clinical manifestations and few effective therapies. Programmed death-1 (PD-1) and its ligands (PD-L1 and PD-L2) protect tissues from immune-mediated damage and permit tumors to evade immune destruction. Therapeutic antibodies against PD-1 and PD-L1 are effective in the treatment of a variety of neoplasms. In the present study, we sought to systematically analyze expression of PD-1 and PD-L1 in a large number of patients with mastocytosis using immunohistochemistry and multiplex fluorescence staining...
February 13, 2018: Blood Advances
https://www.readbyqxmd.com/read/29378171/discriminating-myelodysplastic-syndrome-and-other-myeloid-malignancies-from-non-clonal-disorders-by-multiparametric-analysis-of-automated-cell-data
#20
Seon Young Kim, Yumi Park, Hyunjin Kim, Jimyung Kim, Gye Cheol Kwon, Sun Hoe Koo
BACKGROUND: We investigated the usefulness of novel complete blood count (CBC) data for discriminating myeloid malignancies from non-clonal CBC abnormalities. METHODS: Data were obtained during routine CBC tests of 119 samples from 37 myelodysplastic syndrome (MDS) patients, 92 samples from 45 myeloproliferative neoplasm (MPN) patients, and 15 samples from 11 chronic myelogenous leukemia (CML) patients using a DxH800 (Beckman Coulter). Data obtained from patients with hypocellular bone marrow and from those with other non-clonal diseases with CBC abnormalities were included in the comparisons...
January 26, 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
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