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Chronic myeloproliferative neoplasm

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https://www.readbyqxmd.com/read/28159735/the-microenvironment-in-human-myeloid-malignancies-emerging-concepts-and-therapeutic-implications
#1
Hind Medyouf
Similar to their healthy counterpart, malignant hematopoietic stem cells in myeloid malignancies such as myeloproliferative neoplasms (MPNs), myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), reside in a highly complex and dynamic cellular microenvironment in the bone marrow. This environment provides key regulatory signals for and tightly controls cardinal features of HSCs, including self-renewal, quiescence, differentiation and migration. These features are essential to maintaining cellular homeostasis and blood regeneration throughout life...
February 3, 2017: Blood
https://www.readbyqxmd.com/read/28145534/thrombin-generation-a-potentially-useful-biomarker-of-thrombotic-risk-in-philadelphia-negative-myeloproliferative-neoplasms
#2
Romeo-Gabriel Mihaila
The diagnosis of essential thrombocythemia and polycythemia vera is often made during a thrombotic event which can be serious. Philadelphia-negative chronic myeloproliferative neoplasia patients have an increased thrombotic risk. This is assessed using various scoring systems but these are far from ideal and individual risk. The currend trend to personalised medicine requires finding the most useful thrombotic risk biomarker in these patients. Routine tests for coagulation do not take account of both pro- and anti-coagulant factors which is why these tests are not useful in patients with Philadelphia-negative myeloproliferative neoplasms...
January 6, 2017: Biomedical Papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia
https://www.readbyqxmd.com/read/28113109/pegylated-interferon-alpha-2a-is-clinically-effective-and-tolerable-in-myeloproliferative-neoplasm-patients-treated-off-clinical-trial
#3
K Gowin, T Jain, H Kosiorek, R Tibes, J Camoriano, J Palmer, R Mesa
Polycythemia vera, essential thrombocytosis, and myelofibrosis are chronic Philadelphia-negative myeloproliferative neoplasms that are characterized by clonal hematopoiesis, splenomegaly, risk of hemorrhagic and thrombotic sequelae, and profound symptom burden. We review the outcomes of 75 myeloproliferative neoplasm patients treated with pegylated interferon alpha 2a off study at an academic medical center. In the 56 treated polycythemia vera and essential thrombocytosis patients, a complete or partial response was obtained in 78...
January 5, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28098757/role-of-mir-34a-5p-in-hematopoietic-progenitor-cells-proliferation-and-fate-decision-novel-insights-into-the-pathogenesis-of-primary-myelofibrosis
#4
Elisa Bianchi, Samantha Ruberti, Sebastiano Rontauroli, Paola Guglielmelli, Simona Salati, Chiara Rossi, Roberta Zini, Enrico Tagliafico, Alessandro Maria Vannucchi, Rossella Manfredini
Primary Myelofibrosis (PMF) is a chronic Philadelphia-negative myeloproliferative neoplasm characterized by a skewed megakaryopoiesis and an overproduction of proinflammatory and profibrotic mediators that lead to the development of bone marrow (BM) fibrosis. Since we recently uncovered the upregulation of miR-34a-5p in PMF CD34+ hematopoietic progenitor cells (HPCs), in order to elucidate its role in PMF pathogenesis here we unravelled the effects of miR-34a-5p overexpression in HPCs. We showed that enforced expression of miR-34a-5p partially constrains proliferation and favours the megakaryocyte and monocyte/macrophage commitment of HPCs...
January 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28072764/antitumour-activity-of-trabectedin-in-myelodysplastic-myeloproliferative-neoplasms
#5
Michela Romano, Matteo Giovanni Della Porta, Anna Gallì, Nicolò Panini, Simonetta Andrea Licandro, Ezia Bello, Ilaria Craparotta, Vittorio Rosti, Elisa Bonetti, Richard Tancredi, Marianna Rossi, Laura Mannarino, Sergio Marchini, Luca Porcu, Carlos M Galmarini, Alberto Zambelli, Marco Zecca, Franco Locatelli, Mario Cazzola, Andrea Biondi, Alessandro Rambaldi, Paola Allavena, Eugenio Erba, Maurizio D'Incalci
BACKGROUND: Juvenile myelomonocytic leukaemia (JMML) and chronic myelomonocytic leukaemia (CMML) are myelodysplastic myeloproliferative (MDS/MPN) neoplasms with unfavourable prognosis and without effective chemotherapy treatment. Trabectedin is a DNA minor groove binder acting as a modulator of transcription and interfering with DNA repair mechanisms; it causes selective depletion of cells of the myelomonocytic lineage. We hypothesised that trabectedin might have an antitumour effect on MDS/MPN...
January 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28062906/programmed-cell-death-1-pathway-inhibition-in-myeloid-malignancies-implications-for-myeloproliferative-neoplasms
#6
REVIEW
D C Choi, D Tremblay, C Iancu-Rubin, J Mascarenhas
Myeloproliferative neoplasms (MPNs) are clonal hematopoietic diseases that belong to the spectrum of myeloid malignancies (MyMs), which also include myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and chronic myelogenous leukemia (CML). While hematopoietic stem cell transplantation (HSCT) is a potentially curative therapeutic approach to many MyMs, the associated morbidity and mortality have necessitated the development of non-HSCT therapeutics for symptom management and disease course modification...
January 6, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28056398/clinical-outcome-of-myeloid-sarcoma-in-adult-patients-and-effect-of-allogeneic-stem-cell-transplantation-results-from-a-multicenter-survey
#7
Davide Lazzarotto, Anna Candoni, Carla Filì, Fabio Forghieri, Livio Pagano, Alessandro Busca, Giuseppina Spinosa, Maria Elena Zannier, Erica Simeone, Miriam Isola, Erika Borlenghi, Lorella Melillo, Federico Mosna, Federica Lessi, Renato Fanin
INTRODUCTION: Myeloid Sarcoma (MS) is a rare hematologic myeloid neoplasm that can involve any site of the body. It can occur as an exclusively extramedullary form or it can be associated with an acute myeloid leukemia (AML), a chronic myeloproliferative neoplasm (MPN) or a myelodysplastic syndrome (MDS) at onset or at relapse. The rarity of MS does not enable prospective clinical trials and therefore a specific multicenter register can be useful for the clinical and biological studies of this rare disease...
February 2017: Leukemia Research
https://www.readbyqxmd.com/read/28031530/a-novel-assay-to-detect-calreticulin-mutations-in-myeloproliferative-neoplasms
#8
Valentina Rosso, Jessica Petiti, Enrico Bracco, Roberto Pedrola, Francesca Carnuccio, Elisabetta Signorino, Sonia Carturan, Chiara Calabrese, Giada Bot-Sartor, Michela Ronconi, Anna Serra, Giuseppe Saglio, Francesco Frassoni, Daniela Cilloni
The myeloproliferative neoplasms are chronic myeloid cancers divided in Philadelphia positive (Ph+), chronic myeloid leukemia, or negative: polycythemia vera (PV) essential thrombocythemia (ET), and primary myelofibrosis (PMF). Most Ph negative cases have an activating JAK2 or MPL mutation. Recently, somatic mutations in the calreticulin gene (CALR) were detected in 56-88% of JAK2/MPL-negative patients affected by ET or PMF. The most frequent mutations in CARL gene are type-1 and 2. Currently, CALR mutations are evaluated by sanger sequencing...
January 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28028030/myeloid-neoplasms-with-eosinophilia
#9
REVIEW
Andreas Reiter, Jason Gotlib
Molecular diagnostics has generated substantial dividends in dissecting the genetic basis of myeloid neoplasms with eosinophilia. The family of diseases generated by dysregulated fusion tyrosine kinase (TK) genes is recognized by the World Health Organization (WHO) category, "Myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB, or FGFR1, or with PCM1-JAK2" In addition to myeloproliferative neoplasms (MPN), these patients can present with myelodysplastic syndrome/MPN, as well as de novo or secondary mixed-phenotype leukemias or lymphomas...
February 9, 2017: Blood
https://www.readbyqxmd.com/read/28028025/genomics-of-chronic-neutrophilic-leukemia
#10
REVIEW
Julia E Maxson, Jeffrey W Tyner
Chronic neutrophilic leukemia (CNL) is a distinct myeloproliferative neoplasm with a high prevalence (>80%) of mutations in the colony-stimulating factor 3 receptor (CSF3R). These mutations activate the receptor, leading to the proliferation of neutrophils that are a hallmark of CNL. Recently, the World Health Organization guidelines have been updated to include CSF3R mutations as part of the diagnostic criteria for CNL. Because of the high prevalence of CSF3R mutations in CNL, it is tempting to think of this disease as being solely driven by this genetic lesion...
February 9, 2017: Blood
https://www.readbyqxmd.com/read/28013106/cpx-351-exhibits-potent-and-direct-ex-vivo-cytotoxicity-against-aml-blasts-with-enhanced-efficacy-for-cells-harboring-the-flt3-itd-mutation
#11
Max J Gordon, Paul Tardi, Marc M Loriaux, Stephen E Spurgeon, Elie Traer, Tibor Kovacsovics, Lawrence D Mayer, Jeffrey W Tyner
PURPOSE: Identify AML patients most likely to respond to CPX-351, a nano-scale liposome formulation containing cytarabine and daunorubicin co-encapsulated at a 5:1 molar ratio. METHODS: We examined the ex vivo cytotoxic activity of CPX-351 against leukemic cells isolated from 53 AML patients and an additional 127 samples including acute lymphoblastic leukemia, myelodysplastic syndrome/myeloproliferative neoplasms, or chronic lymphocytic leukemia/lymphoma. We assessed activity with respect to common molecular lesions and used flow cytometry to assess CPX-351 cellular uptake...
December 12, 2016: Leukemia Research
https://www.readbyqxmd.com/read/28010748/psychological-manifestations-of-early-childhood-adversity-in-the-context-of-chronic-hematologic-malignancy
#12
Daniel C McFarland, Megan Johnson Shen, Heather Polizzi, John Mascarenhas, Marina Kremyanskaya, Jimmie Holland, Ronald Hoffman
BACKGROUND: Myeloproliferative neoplasms (MPNs), a group of chronic hematologic malignancies, carry significant physical and psychological symptom burdens that significantly affect patients' quality of life. OBJECTIVES: We sought to identify the relationship between early childhood adversity (ECA) and psychological distress in patients with MPNs, as ECA may compound symptom burden. METHODS: Patients with MPNs were assessed for ECA (i.e., the Risky Families Questionnaire-subscales include abuse/neglect/chaotic home environment), distress (i...
January 2017: Psychosomatics
https://www.readbyqxmd.com/read/27990849/investigation-of-t-cell-immunoglobulin-and-mucin-domain-containing-molecule-3-tim-3-polymorphisms-in-essential-thrombocythaemia-et
#13
Fuyan Han, Guanghai Wang, Yuantang Li, Wenjun Tian, Zhenfang Dong, Shiqing Cheng, Yiqing Liu, Teng Qu, Xiaoying Wang, Yong Wang, Bingchang Zhang, Ying Ju
OBJECTIVES: T-cell immunoglobulin- and mucin-domain-containing molecule-3 (TIM-3) is preferentially expressed on terminally differentiated Th1 cells and inhibits their IFN-γ production. It has been reported that chronic inflammation may be an important driving force for myeloproliferative neoplasms (MPNs). Therefore, we hypothesized that as an important inflammation regulator, TIM-3 may be involved in essential thrombocythaemia (ET). The goal of this study was to investigate whether the -1516G > T, -574G > T and +4259T > G single-nucleotide polymorphisms (SNPs) within the TIM-3 gene contribute to the genetic susceptibility of individuals to ET...
December 17, 2016: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/27990115/urgent-coronary-artery-bypass-surgery-in-a-patient-with-postinfarction-angina-and-active-myelomonocytic-leukaemia
#14
Samuel Anthony Galea, Joseph Galea
Chronic myelomonocytic leukaemia (CMML) is a myelodysplastic/myeloproliferative neoplasm affecting the production and differentiation of the monocyte cell lineage. Cardiac surgery in the context of CMML poses challenges that are not routinely encountered. This is the first reported case in the literature of a patient with active CMML undergoing urgent on-pump coronary artery bypass grafting. A 68-year-old Caucasian man with a history of hypertension, hyperlipidaemia, hypothyroidism, and hypercholesterolaemia, who had been diagnosed by the haematologists with CMML a few months earlier but had remained untreated, underwent urgent surgical coronary revascularisation because of postinfarction angina following a non-ST elevation myocardial infarction associated with troponin I rise...
September 2016: Case Reports in Oncology
https://www.readbyqxmd.com/read/27981789/comparison-of-abnormal-cell-flagging-of-the-hematology-analyzers-sysmex-xn-and-sysmex-xe-5000-in-oncohematologic-patients
#15
J R Furundarena, M Sainz, A Uranga, L Cuevas, I Lopez, J Zubicaray, A Bizjak, N Robado, M Araiz
INTRODUCTION: Hematology analyzers should optimize flagging while minimizing false-negative results and unnecessary microscopic reviews. METHODS: We compared flagging performance of Sysmex XE-5000 and XN analyzers in oncohematologic patients. Differential counts were performed by Cellavision digital system (100 cells) and a hematologist (another 100 cells). RESULTS: First, we included 292 samples (86 with blasts): 28 acute lymphoblastic leukemia, 88 acute myeloid leukemia, 91 myelodysplastic syndromes, 45 chronic myeloproliferative neoplasms, and 40 chronic myelomonocytic leukemia...
February 2017: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/27958278/neutrophil-extracellular-trap-formation-and-circulating-nucleosomes-in-patients-with-chronic-myeloproliferative-neoplasms
#16
Cecilia P Marin Oyarzún, Agostina Carestia, Paola R Lev, Ana C Glembotsky, Miguel A Castro Ríos, Beatriz Moiraghi, Felisa C Molinas, Rosana F Marta, Mirta Schattner, Paula G Heller
The mechanisms underlying increased thrombotic risk in chronic myeloproliferative neoplasms (MPN) are incompletely understood. We assessed whether neutrophil extracellular traps (NETs), which promote thrombosis, contribute to the procoagulant state in essential thrombocythemia, polycythemia vera and myelofibrosis (MF) patients. Although MPN neutrophils showed increased basal reactive oxygen species (ROS), enhanced NETosis by unstimulated neutrophils was an infrequent finding, whereas PMA-triggered NETosis was impaired, particularly in MF, due to decreased PMA-triggered ROS production...
December 13, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27930945/a-phase-ii-study-of-panobinostat-in-patients-with-primary-myelofibrosis-pmf-and-post-polycythemia-vera-essential-thrombocythemia-myelofibrosis-post-pv-et-mf
#17
John Mascarenhas, Lonette Sandy, Min Lu, James Yoon, Bruce Petersen, David Zhang, Fei Ye, Carrie Newsom, Vesna Najfeld, Tsivia Hochman, Judith D Goldberg, Ronald Hoffman
Myelofibrosis is a chronic and progressive myeloproliferative neoplasm characterized by anemia, splenomegaly, debilitating symptoms and leukemic transformation. Ruxolitinib, an oral JAK1/2 inhibitor, is highly effective in ameliorating systemic symptoms and reducing splenomegaly. Current clinical research is focused on the evaluation of agents based on pre-clinical rationale that can result in disease course modification. Panobinostat is a pan-histone deacetylase inhibitor that has demonstrated clinical activity as a single agent in early phase trials of myelofibrosis...
November 30, 2016: Leukemia Research
https://www.readbyqxmd.com/read/27911124/the-impact-of-interferon-alpha2-on-hla-genes-in-patients-with-polycythemia-vera-and-related-neoplasms
#18
Vibe Skov, Caroline Hasselbalch Riley, Mads Thomassen, Lasse Kjær, Thomas Stauffer Larsen, Ole Weis Bjerrum, Torben A Kruse, Hans Carl Hasselbalch
Gene expression profiling in Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) have unraveled significant deregulation of several immune and inflammation genes of potential importance for clonal evolution. Other mechanisms might be downregulation of major histocompatibility class I and II genes used by tumor cells to escape antitumor T-cell-mediated immune responses. Several genes encoding human leukocyte antigen (HLA) class I and II molecules have been shown to be significantly downregulated...
December 2, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27910028/recurrent-cytogenetic-abnormalities-in-myeloproliferative-neoplasms-and-chronic-myeloid-leukemia
#19
John Swansbury
The commonest types of myeloproliferative neoplasm (MPN) have remarkably similar recurrent chromosome abnormalities, but with varying incidence and prognostic implications. After a clear decade of treatment of chronic myeloid leukemia (CML) with tyrosine kinase inhibitors, the differing prognostic implications of abnormalities additional to the Ph chromosome are being revealed. This chapter provides a description of the main chromosome abnormalities in MPN and CML and their clinical implications in a time of rapid changes in both the application of new diagnostic techniques and the introduction of targeted therapies...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27910027/recurrent-cytogenetic-abnormalities-in-acute-myeloid-leukemia
#20
John J Yang, Tae Sung Park, Thomas S K Wan
The spectrum of chromosomal abnormality associated with leukemogenesis of acute myeloid leukemia (AML) is broad and heterogeneous when compared to chronic myeloid leukemia and other myeloid neoplasms. Recurrent chromosomal translocations such as t(8;21), t(15;17), and inv(16) are frequently detected, but hundreds of other uncommon chromosomal aberrations from AML also exist. This chapter discusses 22 chromosomal abnormalities that are common structural, numerical aberrations, and other important but infrequent (less than 1 %) translocations emphasized in the WHO classification...
2017: Methods in Molecular Biology
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