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myeloproliferative neoplasm

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https://www.readbyqxmd.com/read/29148847/emerging-therapeutic-targets-in-myeloproliferative-neoplasms-and-peripheral-t-cell-leukemia-and-lymphomas
#1
Anna Orlova, Bettina Wingelhofer, Heidi A Neubauer, Barbara Maurer, Angelika Berger-Becvar, György Miklós Keserű, Patrick T Gunning, Peter Valent, Richard Moriggl
Hematopoietic neoplasms are often driven by gain-of-function mutations of the JAK-STAT pathway together with mutations of chromatin remodeling and DNA damage control pathways. The interconnection between the JAK-STAT pathway, epigenetic regulation or DNA damage control is still poorly understood in cancer cell biology. Areas covered: Here, we focus on a broader description of mutational insights into myeloproliferative neoplasms and peripheral T-cell leukemia and lymphomas, since sequencing efforts have identified similar combinations of driver mutations in these diseases covering different lineages...
November 17, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29148089/impact-of-gene-mutations-on-treatment-response-and-prognosis-of-acute-myeloid-leukemia-secondary-to-myeloproliferative-neoplasms
#2
G Venton, F Courtier, A Charbonnier, E D'Incan, C Saillard, B Mohty, M J Mozziconacci, D Birnbaum, A Murati, N Vey, J Rey
Acute myeloid leukemias secondary (sAML) to myeloproliferative neoplasms (MPN) have variable clinical courses and outcomes, but remain almost always fatal. Large cohorts of sAML to MPN are difficult to obtain and there is very little scientific literature or prospective trials for determining robust prognostic markers and efficient treatments. We analyzed event-free survival (EFS) and overall survival (OS) of 73 patients with MPN who progressed to sAML, based on their epidemiological characteristics, the preexisting MPN, the different treatments received, the different prognostic groups and the responses achieved according to the ELN, and their mutational status determined by next-generation DNA sequencing (NGS)...
November 17, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/29147619/the-jak2v617f-and-calr-exon-9-mutations-are-shared-immunogenic-neoantigens-in-hematological-malignancy
#3
Morten Orebo Holmström, Hans Carl Hasselbalch, Mads Hald Andersen
Approximately 90% of patients with the hematological malignancies termed the chronic myeloproliferative neoplasms harbor either the JAK2V617F-mutation or CALR exon 9 mutation. Both of these are recognized by T-cells, which make the mutations ideal targets for cancer immune therapy as they are shared antigens.
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29146710/jak2-calr-mpl-and-asxl1-mutational-status-correlates-with-distinct-histologic-features-in-philadelphia-chromosome-negative-myeloproliferative-neoplasms
#4
Waihay J Wong, Robert P Hasserjian, Geraldine S Pinkus, Lawrence J Breyfogle, Ann Mullaly, Olga Pozdnyakova
No abstract text is available yet for this article.
November 16, 2017: Haematologica
https://www.readbyqxmd.com/read/29145678/-thrombocytosis-and-thrombocytopenia-background-and-clinical-relevance
#5
Kai Wille, Parvis Sadjadian, Martin Griesshammer
Due to the central role of platelets in hemostasis, the clinical relevance of quantitative changes in platelet counts (< 150 G/l or > 450 G/l) may be significant. Thrombopoesis (= production of platelets) occurs in the bone marrow, and the hormone thrombopoetin takes control on its regulation.In thrombocytosis, primary causes have to be distinguished from the far more common reactive (= secondary) reasons. The most important form of primary thrombocytosis occurs in myeloproliferative neoplasms especially in essential thrombocythemia (ET)...
November 2017: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/29143068/patient-characteristics-and-outcomes-in-adolescents-and-young-adults-with-classical-philadelphia-chromosome-negative-myeloproliferative-neoplasms
#6
Prajwal Boddu, Lucia Masarova, Srdan Verstovsek, Paolo Strati, Hagop Kantarjian, Jorge Cortes, Zeev Estrov, Sherry Pierce, Naveen Pemmaraju
Little is known about the outcomes of Philadelphia-negative myeloproliferative neoplasms (MPNs) in adolescents and young adults (AYA). We reviewed all patients with essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF) treated at our institution from 1988 to 2016 who were aged 16 to 39 years (AYA) and described their outcomes in comparison to older MPN population. Of 2206 patients, 185 (8.3%) were identified as AYA: 105 (57%) ET, 43 (23%) PV, and 37 (20%) MF. The median age was 33 years [range, 16-39], and median follow-up time 3 years [range, 0...
November 15, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/29134817/the-bcr-abl1-negative-myeloproliferative-neoplasms-a-review-of-jak-inhibitors-in-the-therapeutic-armamentarium
#7
Martin Griesshammer, Parvis Sadjadian
The classical BCR-ABL1-negative myeloproliferative neoplasms (MPN) include primary myelofibrosis (PMF), polycythaemia vera (PV) and essential thrombocythaemia (ET). They are characterized by stem cell-derived clonal proliferation, harbour Janus kinase 2 (JAK2), or calreticulin (CALR), or myeloproliferative leukaemia virus oncogene (MPL) driver mutations and exert an over activated JAK-signal transducer and activator of transcription (STAT) pathway. Therefore JAK inhibiting strategies have been successfully investigated in MPN clinical trials...
November 14, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/29134664/a-phase-ii-trial-of-ruxolitinib-in-combination-with-azacytidine-in-myelodysplastic-syndrome-myeloproliferative-neoplasms
#8
Rita Assi, Hagop M Kantarjian, Guillermo Garcia-Manero, Jorge E Cortes, Naveen Pemmaraju, Xuemei Wang, Graciela Nogueras-Gonzalez, Elias Jabbour, Prithviraj Bose, Tapan Kadia, Courtney D Dinardo, Keyur Patel, Carlos Bueso-Ramos, Lingsha Zhou, Sherry Pierce, Romany Gergis, Carla Tuttle, Gautam Borthakur, Zeev Estrov, Rajyalakshmi Luthra, Juliana Hidalgo-Lopez, Srdan Verstovsek, Naval Daver
Ruxolitinib and azacytidine target distinct disease manifestations of myelodysplastic syndrome/myeloproliferative neoplasms (MDS/MPNs). Patients with MDS/MPNs initially received ruxolitinib BID (doses based on platelets count), continuously in 28-day cycles for the first 3 cycles. Azacytidine 25 mg/m(2) (Day 1-5) intravenously or subcutaneously was recommended to be added to each cycle starting cycle 4 and could be increased to 75 mg/m(2) (Days 1-5) for disease control. Azacytidine could be started earlier than cycle 4 and/or at higher dose in patients with rapidly proliferative disease or with elevated blasts...
November 14, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/29129488/dna-hypomethylating-agents-as-epigenetic-therapy-before-and-after-allogeneic-hematopoietic-stem-cell-transplantation-in-myelodysplastic-syndromes-and-juvenile-myelomonocytic-leukemia
#9
REVIEW
Christian Flotho, Sebastian Sommer, Michael Lübbert
Myelodysplastic syndrome (MDS) is a clonal bone marrow disorder, typically of older adults, which is characterized by ineffective hematopoiesis, peripheral blood cytopenias and risk of progression to acute myeloid leukemia. Juvenile myelomonocytic leukemia (JMML) is an aggressive myeloproliferative neoplasm occurring in young children. The common denominator of these malignant myeloid disorders is the limited benefit of conventional chemotherapy and a particular responsiveness to epigenetic therapy with the DNA-hypomethylating agents 5-azacytidine (azacitidine) or decitabine...
November 9, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29128551/transplant-decisions-in-patients-with-myelofibrosis-should-mutations-be-the-judge
#10
REVIEW
Rachel B Salit, H Joachim Deeg
The prognosis of myeloproliferative neoplasms (MPN), including primary myelofibrosis (PMF), polycythemia vera (PV; post-PV MF) and essential thrombocythemia (ET; post-EMF) varies considerably, between these disorders as well as within each diagnosis. Molecular studies have identified "driver mutations", in JAK2, MPL1 and CALR, and additional somatic DNA mutations, including ASXL1, EZH2, IDH1/2 and SRSF2, that affect prognosis differentially. Patients with mutations in CALR (type1) have a better outlook than patients with mutations in JAK2 or MPL, while patients without any of the driver mutations (triple negative) have the shortest life expectancy...
November 8, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29124948/tasigna-nilotinib-in-chronic-myeloid-leukemia%C3%A2-treatment-free-remission-after-nearly-2%C3%A2-years-an-interview-with-adam-mead
#11
Adam Mead
Dr Mead earned his medical degree from the University of Oxford and trained in hematology at St Bartholomew's Hospital and University College London. In 2007, he earned his PhD at UCL, which focused on the analysis of FLT3 mutations in acute myeloid leukemia. He is now Associate Professor of Hematology and MRC Senior Clinical Fellow at the WIMM, University of Oxford. His research group focuses on myeloid diseases and normal blood stem-cell biology. Dr Mead is the lead clinician for myeloproliferative neoplasms (MPN) and chronic myeloid leukemia in the Thames Valley Strategic Clinical Network and is the chief investigator for several chronic myeloid leukemia and MPN clinical trials...
November 10, 2017: Future Oncology
https://www.readbyqxmd.com/read/29121538/therapeutic-options-for-leukemic-transformation-in-patients-with-myeloproliferative-neoplasms
#12
REVIEW
Maliha Khan, Rabbia Siddiqi, Naseema Gangat
Approximately 5-10% of patients with Philadelphia chromosome negative myeloproliferative neoplasms (MPN) comprising of essential thrombocythemia, polycythemia vera and primary myelofibrosis) experience transformation to acute myeloid leukemia (AML, ≥20% blasts). Treatment options for post-MPN AML patients are limited, as conventional approaches like standard chemotherapy, fail to offer long-term benefit. Median survival for secondary AML is ∼2.4 months. Post-MPN AML therefore represents an area of urgent clinical need...
October 27, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29119847/myeloid-lymphoid-neoplasms-with-fgfr1-rearrangement
#13
Paolo Strati, Guilin Tang, Dzifa Y Duose, Saradhi Mallampati, Rajyalakshmi Luthra, Keyur P Patel, Mohammad Hussaini, Abu-Sayeef Mirza, Rami S Komrokji, Stephen Oh, John Mascarenhas, Vesna Najfeld, Vivek Subbiah, Hagop Kantarjian, Guillermo Garcia-Manero, Srdan Verstovsek, Naval Daver
Myeloid/lymphoid neoplasms with FGFR1 rearrangement are a rare entity. We present a multicenter experience of 17 patients with FISH-confirmed FGFR1 rearrangement. The clinical presentation at diagnosis included myeloproliferative neoplasm (MPN) in 4 (24%) patients, acute leukemia (AL) in 7 (41%), and concomitant MPN with AL in 6 (35%). The two most frequently observed cytogenetic abnormalities were t(8;13)(p11.2;q12)(partner gene ZMYM2) and t(8;22)(p11.2; q11.2)(BCR). Seventy-eight percent of tested patients had a RUNX1 mutation, of whom all had AL...
November 9, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29115897/next-generation-sequencing-discriminates-myelodysplastic-myeloproliferative-neoplasms-from-paraneoplastic-leukemoid-reaction-in-cancer-patients-with-hyperleukocytosis
#14
Riwa Sakr, Aline Renneville, Veronique Saada, Sophie Cotteret, Jean-Edouard Martin, Nathalie Droin, Dorothée Selimoglu-Buet, Benjamin Besse, Antoine Hollebecque, Christophe Marzac, Florence Pasquier, Jean-Baptiste Micol, Stéphane De Botton, Olivier Mir, Eric Solary, Christophe Willekens
No abstract text is available yet for this article.
November 8, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29108292/azacitidine-or-intensive-chemotherapy-for-older-patients-with-secondary-or-therapy-related-acute-myeloid-leukemia
#15
Pierre-Yves Dumas, Sarah Bertoli, Emilie Bérard, Clémence Médiavilla, Edwige Yon, Suzanne Tavitian, Thibaut Leguay, Françoise Huguet, Edouard Forcade, Noël Milpied, Audrey Sarry, Mathieu Sauvezie, Pierre Bories, Arnaud Pigneux, Christian Récher
The treatment of older patients with acute myeloid leukemia that is secondary to previous myelodysplastic syndrome, myeloproliferative neoplasm, or prior cytotoxic exposure remains unsatisfactory. We compared 92 and 107 patients treated, respectively, with intensive chemotherapy or azacitidine within two centres. Diagnoses were 37.5% post-myelodysplastic syndrome, 17.4% post-myeloproliferative neoplasia, and 45.1% therapy-related acute myeloid leukemia. Patients treated by chemotherapy had less adverse cytogenetics, higher white blood-cell counts, and were younger: the latter two being independent factors entered into the multivariate analyses...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29107667/fgfr1-translocation-with-concurrent-myeloproliferative-neoplasm-systemic-mastocytosis-and-lymphoblastic-lymphoma-a-case-report
#16
Koping Chang, Jia-Hau Liu, Shan-Chi Yu, Chung-Wu Lin
FGFR1 translocation may cause myeloid or lymphoid neoplasm but rarely systemic mastocytosis (SM). Conversely, SM is associated with myeloproliferative neoplasm (MPN), but rarely lymphoblastic lymphoma (LBL) or FGFR1 translocation. We report the first case of FGFR1 translocation in a patient with concurrent LBL, MPN, and SM. A 21-year-old male patient presented with diffuse lymphadenopathies and leukocytosis. TdT(+)/cytoCD3(+)/CD79a(weakly+) LBL was identified in the lymph node. Bone marrow had MPN, SM, and TdT(+)/CD79a(+)/cytoCD3(weakly+) LBL...
October 28, 2017: Human Pathology
https://www.readbyqxmd.com/read/29107666/jak2-mutated-langerhans-cell-histiocytosis-associated-with-primary-myelofibrosis-treated-with-ruxolitinib
#17
Arturo Bonometti, Filippo Bagnoli, Daniele Fanoni, Luigia Venegoni, Laura Corti, Paola Bianchi, Elena Maria Elli, Giuseppe Isimbaldi, Vincenzo L'Imperio, Gianluca Nazzaro, Emanuela Passoni, Emilio Berti
The pathogenesis and cellular origin of Langerhans cell histiocytosis (LCH) are debated. Recently, mutations on MAPK and PI3K pathways have been linked to disrupted cell proliferation in LCH. Janus Kinase 2 (JAK2) mutations play the same role in Philadelphia-negative chronic myeloproliferative neoplasms. We describe the case of a patient affected by JAK2-positive Primary Myelofibrosis (PMF) who developed a clonally related LCH while in treatment with Ruxolitinib. JAK-inhibitors are well known to affect function and differentiation of different hematological lineages, including mononuclear phagocytes precursors...
October 28, 2017: Human Pathology
https://www.readbyqxmd.com/read/29105027/rare-cancers-and-social-media-analysis-of-twitter-metrics-in-the-first-2%C3%A2-years-of-a-rare-disease-community-for-myeloproliferative-neoplasms-on-social-media-mpnsm
#18
REVIEW
Naveen Pemmaraju, Audun Utengen, Vikas Gupta, Jean-Jacques Kiladjian, Ruben Mesa, Michael A Thompson
PURPOSE OF REVIEW: The use of social media has now become a standard 13 means of communication for many individuals worldwide. 14 The use of one specific form of social media, Twitter, has 15 increased among healthcare providers, both as a means of 16 information gathering and as a conduit for original content 17 creation. Recently, major efforts by users have been put for- 18 ward to help streamline the unprecedented amount of infor- 19 mation that can be found on Twitter. These efforts have led to 20 the creation of diseasespecific hashtag (#) medical communi- 21 ties and have greatly enhanced the ability to understand and 22 better categorize the available data on Twitter...
November 6, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/29104287/risk-of-developing-chronic-myeloid-neoplasms-in-well-differentiated-thyroid-cancer-patients-treated-with-radioactive-iodine
#19
R J Molenaar, C Pleyer, T Radivoyevitch, S Sidana, A Godley, A S Advani, A T Gerds, H E Carraway, M Kalaycio, A Nazha, D Adelstein, C Nasr, D Angelini, J P Maciejewski, N Majhail, M A Sekeres, S Mukherjee
Exposure to ionizing radiation increases the risk of myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN), but such risks are not known in well-differentiated thyroid cancer (WDTC) patients treated with radioactive iodine (RAI). A total of 148 215 WDTC patients were identified from Surveillance Epidemiology and End Results (SEER) registries between 1973 and 2014, of whom 54% underwent definitive thyroidectomy and 46% received adjuvant RAI. With a median follow-up of 6.6 years, 77 and 66 WDTC patients developed MDS and MPN, respectively...
November 6, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29100304/germline-variations-at-jak2-tert-hbs1l-myb-and-mecom-and-the-risk-of-myeloproliferative-neoplasms-in-taiwanese-population
#20
Yi-Hao Chiang, Yu-Cheng Chang, Huan-Chau Lin, Ling Huang, Chun-Chia Cheng, Wei-Ting Wang, Hung-I Cheng, Nai-Wen Su, Caleb Gon-Shen Chen, Johnson Lin, Yi-Fang Chang, Ming-Chih Chang, Ruey-Kuen Hsieh, Wen-Chien Chou, Ken-Hong Lim, Yuan-Yeh Kuo
Germline variations at JAK2, TERT, HBS1L-MYB and MECOM have been found to associate with myeloproliferative neoplasms (MPNs) in European populations. Whether these germline variations are associated with MPNs in Taiwanese population is obscure. Here we aimed to evaluate the association of five germline variations (JAK2 46/1 haplotype tagged by rs12343867, JAK2 intron 8 rs12339666, TERT rs2736100, HBS1L-MYB rs9376092 and MECOM rs2201862) and the risk of MPNs in Taiwanese population. A total of 178 MPN patients (109 essential thrombocythemia, 54 polycythemia vera and 15 primary myelofibrosis) were enrolled into this study...
September 29, 2017: Oncotarget
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