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Chronic myeloproliferative neoplasm

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https://www.readbyqxmd.com/read/28338652/3q26-2-evi1-rearrangement-is-associated-with-poor-prognosis-in-classical-philadelphia-chromosome-negative-myeloproliferative-neoplasms
#1
Zhihong Hu, L Jeffrey Medeiros, Wei Wang, Zi Chen, Guilin Tang, Parsa Hodjat, Su Yang, Lianghua Fang, Yan Li, Srdan Verstovsek, Shimin Hu
Classical Philadelphia chromosome-negative myeloproliferative neoplasms are a group of closely related myeloid disorders with different histologic features and clinical presentations at an early stage, but all later develop into a similar fibrotic stage with variable risk of acute transformation. The significance of 3q26.2/EVI1 rearrangement has been well recognized in acute myeloid leukemia, myelodysplastic syndrome, and chronic myeloid leukemia. However, the clinical importance of 3q26.2/EVI1 rearrangement in classical Philadelphia chromosome-negative myeloproliferative neoplasms is unknown...
March 24, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28335073/clinical-characteristics-and-whole-exome-transcriptome-sequencing-of-coexisting-chronic-myeloid-leukemia-and-myelofibrosis
#2
Malathi Kandarpa, Yi-Mi Wu, Dan Robinson, Patrick William Burke, Arul M Chinnaiyan, Moshe Talpaz
Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell (HSC) disorders that can be classified on the basis of genetic, clinical, phenotypic features. Genetic lesions such as JAK2 mutations and BCR-ABL translocation are often mutually exclusive in MPN patients and lead to essential thrombocythemia, polycythemia vera or myelofibrosis (ET/PV/MF) or chronic myeloid leukemia, respectively. Nevertheless, coexistence of these genetic aberrations in the same patient has been reported. Whether these aberrations occur in the same stem cell or a different cell is unclear, but an unstable genome in the HSCs seems to be the common antecedent...
March 23, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28314085/targeted-next-generation-sequencing-and-identification-of-risk-factors-in-world-health-organization-defined-atypical-chronic-myeloid-leukemia
#3
Mrinal M Patnaik, Daniela Barraco, Terra L Lasho, Christy M Finke, Kaaren Reichard, Katherine P Hoversten, Rhett P Ketterling, Naseema Gangat, Ayalew Tefferi
Atypical chronic myeloid leukemia (aCML) is an aggressive myeloid neoplasm with overlapping features of myelodysplastic syndromes (prominent granulocytic dysplasia) and myeloproliferative neoplasms (neutrophilic leukocytosis). We studied 25 molecularly-annotated and World Health Organization defined aCML patients; median age 70 years, 84% males. Cytogenetic abnormalities were seen in 36% and gene mutations in 100%. Mutational frequencies were, ASXL1 28%, TET2 16%, NRAS 16%, SETBP1 12%, RUNX1 12%, ETNK1 8% and PTPN11 4%...
March 17, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28298076/chronic-kidney-disease-in-the-bcr-abl1-negative-myeloproliferative-neoplasm-a-single-center-retrospective-study
#4
Seung-Woo Baek, Ji Young Moon, Hyewon Ryu, Yoon-Seok Choi, Ik-Chan Song, Hyo-Jin Lee, Hwan-Jung Yun, Samyoung Kim, Deog-Yeon Jo
Background/Aims: Renal complications related to BCR-ABL1-negative myeloproliferative neoplasms (MPNs) have not been examined fully in Asian populations. Methods: We analyzed estimated glomerular filtration rate (eGFR) and its changes with time retrospectively in patients with BCR-ABL1-negative MPN from 2005 to 2015. Results: The prevalence of chronic kidney disease (CKD) was 11% (6.6% having stage 3 and 4.4% having stage 4). In a linear regression analysis of eGFR versus time (years), overall, patients showed increased eGFR (mL/min/1...
March 17, 2017: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/28292946/nox2-dependent-immunosuppression-in-chronic-myelomonocytic-leukemia
#5
Johan Aurelius, Alexander Hallner, Olle Werlenius, Rebecca Riise, Lars Möllgård, Mats Brune, Markus Hansson, Anna Martner, Fredrik B Thorén, Kristoffer Hellstrand
Chronic myelomonocytic leukemia (CMML) is a myeloproliferative and myelodysplastic neoplasm with few treatment options and dismal prognosis. The role of natural killer (NK) cells and other antileukemic lymphocytes in CMML is largely unknown. We aimed to provide insight into the mechanisms of immune evasion in CMML with a focus on immunosuppressive reactive oxygen species (ROS) formed by the myeloid cell NADPH oxidase-2 (NOX2). The dominant population of primary human CMML cells was found to express membrane-bound NOX2 and to release ROS, which, in turn, triggered extensive PARP-1-dependent cell death in cocultured NK cells, CD8(+) T effector memory cells, and CD8(+) T effector cells...
March 14, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28276292/chronic-myelogenous-leukemia-presenting-as-a-secondary-malignancy-after-bcr-abl1-negative-b-lymphoblastic-leukemia-lymphoma-in-a-pediatric-patient
#6
Gheorghe Popa, Cristina Blag, Horatiu Olteanu
Chronic myelogenous leukemia, BCR-ABL1 positive (CML) is a rare myeloproliferative neoplasm in children and presents even less often as a secondary malignancy in the pediatric population. Below, we report a patient with Philadelphia-negative B-lymphoblastic leukemia/lymphoma, who developed CML several years after achieving complete remission, and summarize the existing literature on the clinical and pathologic features of CML as a secondary pediatric malignancy.
January 2017: Pediatric and Developmental Pathology
https://www.readbyqxmd.com/read/28273188/-treatment-options-and-limitations-in-the-management-of-myelofibrosis
#7
Gábor Körösmezey, Gabriella Gyõri, Gábor Rudas, Hanna Eid, Zsolt Nagy, Judit Demeter
Primary myelofibrosis has the worst outcome among classical chronic myeloproliferative neoplasms. The past decade has brought numerous discoveries elucidating the role of proliferative mutations in disease pathogenesis. Mutations of the genes JAK2, MPL and CALR are present in about 90 percent of all primary myelofibrosis cases. The prognosis of myelofibrosis is considered heterogeneous, the expected survival of patients may range from one year to more than a decade based on several prognostic factors. Estimated survival can be assessed based on clinical prognostic scores...
March 8, 2017: Magyar Onkologia
https://www.readbyqxmd.com/read/28245393/-mutation-of-calr-gene-in-patients-with-chronic-myeloproliferative-neoplasm-and-its-clinical-significance
#8
Qin Tang, Xiu-Wen Zhang, Lei Xia, Nai-Ke Jiang
OBJECTIVE: To analyze the CARL gene mutation in the patients with chronic myeloproliferative neoplasm(MPN) and to explore the clinical significance of CALR mutation. METHODS: The peripheral blood of patients was collected and the genomic DNA was exacted, the 9 exon of CALR gene and the fragment of human thrombopoetic receptor(MPL) gene were amplified by PCR, the mutation of CALR and MPL genes was detected by using the direct sequencing, the JAK2 V617F mutation was detected by using allele spicific PCR...
February 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28228104/driver-mutations-jak2v617f-mplw515l-k-or-calr-pentraxin-3-and-c-reactive-protein-in-essential-thrombocythemia-and-polycythemia-vera
#9
Federico Lussana, Alessandra Carobbio, Silvia Salmoiraghi, Paola Guglielmelli, Alessandro Maria Vannucchi, Barbara Bottazzi, Roberto Leone, Alberto Mantovani, Tiziano Barbui, Alessandro Rambaldi
BACKGROUND: The driver mutations JAK2V617F, MPLW515L/K and CALR influence disease phenotype of myeloproliferative neoplasms (MPNs) and might sustain a condition of chronic inflammation. Pentraxin 3 (PTX3) and high-sensitivity C-reactive protein (hs-CRP) are inflammatory biomarkers potentially useful for refining prognostic classification of MPNs. METHODS: We evaluated 305 with essential thrombocythemia (ET) and 172 polycythemia vera (PV) patients diagnosed according to the 2016 WHO criteria and with full molecular characterization for driver mutations...
February 22, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28218607/tet2-asxl1-idh1-and-idh2-single-nucleotide-polymorphisms-in-turkish-patients-with-chronic-myeloproliferative-neoplasms
#10
Nur Soyer, Burçin Tezcanlı Kaymaz, Melda Cömert Özkan, Çağdaş Aktan, Ali Şahin Küçükaslan, Fahri Şahin, Buket Kosova, Güray Saydam
We aimed to determine the genotype distribution, allele frequency and prognostic impact of IDH1/2(Isocitrate dehydrogenase), TET2(Ten-Eleven-Translocation2) and ASXL1(Additional Sex Combs-Like 1) single nucleotide polymorphisms (SNPs) in MPNs. TET2(rs763480), ASXL1(rs2208131) and IDH1(rs11554137) variant homozygous genotype frequencies were 1.5%, 9.2% and 2.3%, respectively. No IDH2 SNP was identified. IDH1 and TET2 frequencies were 5% in ET and 1.7% in ET, 5% in PMF, respectively. ASXL1 frequencies were 8...
February 20, 2017: Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology
https://www.readbyqxmd.com/read/28159735/the-microenvironment-in-human-myeloid-malignancies-emerging-concepts-and-therapeutic-implications
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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