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myeloproliferative chronic neoplasm

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https://www.readbyqxmd.com/read/30479769/philadelphia-chromosome-positive-aml-arising-from-jak2-positive-myelofibrosis
#1
Marte Karen Brattås, Kyrre Lilleeng, Randi Hovland, Ingvild Jenssen Lægreid, Marta Vorland, Friedemann Leh, Øystein Bruserud, Bjørn Tore Gjertsen, Håkon Reikvam
Background: A feature of myeloproliferative neoplasia is transforming to more aggressive and malignant myeloid neoplasia, including acute myeloid leukemia. Different pathogenesis mechanisms participate in transformation, including transformation of existing potential preleukemic clones, since JAK2 -mutant myeloproliferative neoplasms often transform to JAK2 wild-type acute myeloid leukemia. Case presentation: Here, we present an 80 year old man with a JAK2 -V617F mutant primary myelofibrosis...
2018: Biomarker Research
https://www.readbyqxmd.com/read/30477631/-advances-in-the-treatment-of-juvenile-myelomonocytic-leukemia
#2
Yu-Li Cai, Jing-Liao Zhang, Xiao-Fan Zhu
Juvenile myelomonocytic leukemia (JMML) is a rare chronic myeloid leukemia in children and has the features of both myelodysplastic syndrome and myeloproliferative neoplasm. It is highly malignant and has a poor treatment outcome. Children with JMML have a poor response to conventional chemotherapy. At present, hematopoietic stem cell transplantation is the only possible cure for this disease. In recent years, significant progress has been made in targeted therapy for mutant genes in the Ras signaling pathway and demethylation treatment of aberrant methylation of polygenic CpG islands...
November 2018: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/30473959/colony-stimulating-factor-3-receptor-mutated-chronic-neutrophilic-leukemia-a-rare-case-report
#3
Bicky Thapa, Christopher Jamhour, Johnny Chahine, Heesun J Rogers, Hamed Daw
Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative neoplasm, which is characterized by sustained peripheral leukocytosis with neutrophilia, hepatosplenomegaly, and hypercellularity of the bone marrow, with less than 5% myeloblasts along with normal neutrophil maturation and no dysplasia. In 2016, World Health Organization (WHO) included activating mutations in the gene for colony-stimulating factor 3 receptor (CSF3R) as one of the diagnostic criteria with CSF3RT618I being the most common mutation...
September 18, 2018: Curēus
https://www.readbyqxmd.com/read/30463063/unique-case-of-myeloproliferative-neoplasm-with-two-rare-clonal-abnormalities-rare-jak2-exon-12-mutation-and-rare-e14a3-b3a3-bcr-abl-fusion-transcript
#4
Mahesh Swaminathan, Keyur P Patel, Julie Huynh-Lu, Guilin Tang, Zhuang Zuo, Roberto Miranda, Srdan Verstovsek
Myeloproliferative neoplasms (MPNs) are clonal disorders divided into Philadelphia (Ph) chromosome-positive chronic myeloid leukemia (CML) or Ph chromosome-negative MPNs. Co-occurrence of these disease entities is very rare and typically involves presence of common p190 or p210 BCR/ABL fusion transcript (responsible for CML) along with JAK2V617F mutation (most common driver mutation in Ph-negative MPNs). Because of the rarity of such cases, it is not clear if the outcomes are any different in these patients...
November 21, 2018: Acta Haematologica
https://www.readbyqxmd.com/read/30452397/analysis-of-clinical-characteristics-of-bone-marrow-proliferative-tumor-progression-to-acute-myeloid-leukemia
#5
Ying Li, Xi-Yuan Zhang, Jie Han, Ling Wang
OBJECTIVE: This study aims to analyze Chinese patients who developed acute leukemia after being diagnosed and treated for Philadelphia chromosome (Ph)-negative chronic myeloproliferative neoplasms (MPNs), and compare the findings of this series with similar studies from literature. METHODS: Nine patients who progressed to leukemia after being diagnosed with MPN were included into the present study. Clinical data including age, treatment modalities and duration of use in the myeloproliferative phase, latency to leukemic transformation (LT), characteristics of leukemia, chemotherapy administration, and survival after LT were examined...
November 4, 2018: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/30423295/jarid2-functions-as-a-tumor-suppressor-in-myeloid-neoplasms-by-repressing-self-renewal-in-hematopoietic-progenitor-cells
#6
Hamza Celik, Won Kyun Koh, Ashley C Kramer, Elizabeth L Ostrander, Cates Mallaney, Daniel A C Fisher, Jingyu Xiang, William C Wilson, Andrew Martens, Alok Kothari, Gregory Fishberger, Eric Tycksen, Darja Karpova, Eric J Duncavage, Youngsook Lee, Stephen T Oh, Grant A Challen
How specific genetic lesions contribute to transformation of non-malignant myeloproliferative neoplasms (MPNs) and myelodysplastic syndromes (MDSs) to secondary acute myeloid leukemia (sAML) are poorly understood. JARID2 is lost by chromosomal deletions in a proportion of MPN/MDS cases that progress to sAML. In this study, genetic mouse models and patient-derived xenografts demonstrated that JARID2 acts as a tumor suppressor in chronic myeloid disorders. Genetic deletion of Jarid2 either reduced overall survival of animals with MPNs or drove transformation to sAML, depending on the timing and context of co-operating mutations...
November 12, 2018: Cancer Cell
https://www.readbyqxmd.com/read/30416690/the-jak2v617f-point-mutation-increases-the-osteoclast-forming-ability-of-monocytes-in-patients-with-chronic-myeloproliferative-neoplasms-and-makes-their-osteoclasts-more-susceptible-to-jak2-inhibition
#7
Emmanouil Spanoudakis, Menelaos Papoutselis, Ioanna Bazdiara, Eleftheria Lamprianidi, Xrisa Kordella, Constantinos Tilkeridis, Costas Tsatalas, Ioannis Kotsianidis
JAK2V617F is a gain of function point mutation that occurs in Myeloproliferative Neoplasm (MPN) patients and deranges their hemopoiesis at cellular level. We speculate that hyperfunctioning JAK2 can modify osteoclast (OCL) homeostasis in MPN patients. We studied 18 newly diagnosed MPN patients and four age-matched normal donors (ND). Osteoclast forming assays started from selected monocytes also and under titrated concentrations of the JAK2 Inhibitor AG-490 (Tyrphostin). Genomic DNA was extracted from the formed osteoclasts, and the JAK2V617F/JAK2WT genomic DNA ratio was calculated...
2018: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/30405096/prefibrotic-myelofibrosis-treatment-algorithm-2018
#8
REVIEW
Guido Finazzi, Alessandro M Vannucchi, Tiziano Barbui
Prefibrotic myelofibrosis (pre-PMF) is a distinct entity among chronic myeloproliferative neoplasm diagnosed according to the revised 2016 WHO classification. The clinical picture is heterogeneous, ranging from isolated thrombocytosis, mimicking essential thrombocythemia (ET), to symptoms of high-risk PMF. Retrospective studies showed that survival of patients with pre-PMF is worse than that of ET and better than overt PMF. Whilst a specific prognostic score is lacking, the International Prognostic Scoring System is able to predict survival in pre-PMF patients, yet failing to separate intermediate-1 and -2 groups, and can be used in clinical practice...
November 7, 2018: Blood Cancer Journal
https://www.readbyqxmd.com/read/30384359/successful-decitabine-treatment-in-unfit-elderly-patients-with-acute-myeloid-leukemia-following-chronic-myeloproliferative-neoplasm
#9
Elisabetta Abruzzese, Malgorzata Monika Trawinska, Benedetta Neri, Francesco Bondanini, Stefano Fratoni, Andrea Tendas, Laura Scaramucci, Agostina Siniscalchi, Marco Giovannini, Roberto Palumbo, Paolo de Fabritiis, Pasquale Niscola
No abstract text is available yet for this article.
November 1, 2018: Acta Haematologica
https://www.readbyqxmd.com/read/30367142/using-patient-derived-ipscs-to-develop-humanized-mouse-models-for-chronic-myelomonocytic-leukemia-and-therapeutic-drug-identification-including-liposomal-clodronate
#10
Kazuki Taoka, Shunya Arai, Keisuke Kataoka, Masataka Hosoi, Masashi Miyauchi, Sho Yamazaki, Akira Honda, Wei Aixinjueluo, Takashi Kobayashi, Keiki Kumano, Akihide Yoshimi, Makoto Otsu, Akira Niwa, Tatsutoshi Nakahata, Hiromitsu Nakauchi, Mineo Kurokawa
Chronic myelomonocytic leukemia (CMML) is an entity of myelodysplastic syndrome/myeloproliferative neoplasm. Although CMML can be cured with allogeneic stem cell transplantation, its prognosis is generally very poor due to the limited efficacy of chemotherapy and to the patient's age, which is usually not eligible for transplantation. Comprehensive analysis of CMML pathophysiology and the development of therapeutic agents have been limited partly due to the lack of cell lines in CMML and the limited developments of mouse models...
October 26, 2018: Scientific Reports
https://www.readbyqxmd.com/read/30357754/cml-with-megakaryocytic-blast-crisis-report-of-3-cases
#11
Rashi Khemka, Monica Gupta, Nehar Kanta Jena
Chronic myelogenous leukemia (CML) is a chronic myeloproliferative neoplasm consistently associated with the BCR-ABL1 fusion gene located in the Philadelphia chromosome. The Blast Phase is diagnosed when blasts are ≥20% of the peripheral blood white cell count or of bone marrow nucleated cells or when there is an extramedullary blast proliferation. Megakaryocytic blast crisis as the presenting manifestation of CML is extremely rare and only 7 reported cases were found in the literature. Out of 34 cases of CML-Blast Phase between April 2015 and June 2016, 3 cases showed megakaryocytic differentiation...
October 25, 2018: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/30353413/leukemic-transformation-of-myeloproliferative-neoplasms-therapeutic-and-genomic-considerations
#12
REVIEW
Bing Li, John O Mascarenhas, Raajit K Rampal
PURPOSE OF REVIEW: Although BCR-ABL1-negative myeloproliferative neoplasms (MPN) are chronic, clonal hematopoietic stem cell (HSC) disorders marked by proliferation of one or more myeloid lineages, a substantial proportion of patients transform to acute myeloid leukemia. Leukemic transformation (LT) from a pre-existing MPN carries a dismal prognosis. Here, we review recent genetic, biological, and clinical data regarding LT. RECENT FINDINGS: In the last decade, DNA sequencing has revolutionized our understanding of the genomic landscape of LT...
October 23, 2018: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/30329092/can-platelet-distribution-width-be-used-to-predict-the-possibility-of-chronic-myeloproliferative-neoplasms
#13
Vani Chandrashekar, Anil Tarigopula
Platelet distribution width (PDW) and mean platelet volume are markers of platelet activation and have prognostic value in coronary heart diseases, as well as in cancers of solid organs. In this study, we evaluated the possibility of using PDW to predict chronic myeloproliferative neoplasms by comparing platelet indices obtained by automated analyzers in chronic myeloproliferative neoplasms with those in control specimens. We found that PDW greater than 66.4% has specificity of 99% and likelihood ratio of 19...
October 17, 2018: Laboratory Medicine
https://www.readbyqxmd.com/read/30327374/the-mutational-landscape-of-accelerated-and-blast-phase-myeloproliferative-neoplasms-impacts-patient-outcomes
#14
Caroline J McNamara, Tony Panzarella, James A Kennedy, Andrea Arruda, Jaime O Claudio, Georgina Daher-Reyes, Jenny Ho, Nancy Siddiq, Rebecca Devlin, Hubert Tsui, Jie Su, Tracy Stockley, Mahadeo Sukhai, Nisha Kanwar, Steven Chan, Dawn Maze, Aaron Schimmer, Andre Schuh, Hassan Sibai, Auro Viswabandya, Karen Yee, Mark D Minden, Suzanne Kamel-Reid, Vikas Gupta
There is a paucity of data regarding the impact of mutations on outcomes in accelerated-phase (AP) and blast-phase (BP) myeloproliferative neoplasms (MPNs). Moreover, it is unknown whether mutational status affects survival, as seen in chronic-phase MPNs. Therefore, we performed a retrospective analysis of all patients treated at our institution with AP/BP MPNs (N = 122; AP = 14; BP = 108) to comprehensively describe the mutational profile and correlate with clinical outcomes. Targeted sequencing with a 54-gene panel was performed...
October 23, 2018: Blood Advances
https://www.readbyqxmd.com/read/30319826/chronic-myeloid-leukemia-and-cesarean-section-the-anesthesiologist-s-point-of-view
#15
Houssam Rebahi, Mourad Ait Sliman, Ahmed-Rhassane El Adib
Background: Chronic Myeloid Leukemia (CML) is a myeloproliferative neoplasm related to chromosomal reciprocal translocation t(9;22). Tyrosine kinase inhibitors (TKIs) such as imatinib have drastically revolutionized the course and the prognosis of this hematologic malignancy. As we know, the association pregnancy-CML is an infrequent situation. Also the use of TKI in pregnant women is unsafe with a lack of alternatives and effective therapeutic options. Thus its cessation during gestation puts those patients at high risk of developing blast crisis characterized by poor outcomes...
2018: Case Reports in Obstetrics and Gynecology
https://www.readbyqxmd.com/read/30304859/epigenetic-modifiers-in-myeloid-malignancies-the-role-of-histone-deacetylase-inhibitors
#16
REVIEW
Johanna S Ungerstedt
Myeloid hematological malignancies are clonal bone marrow neoplasms, comprising of acute myeloid leukemia (AML), the myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), the myeloproliferative neoplasms (MPN) and systemic mastocytosis (SM). The field of epigenetic regulation of normal and malignant hematopoiesis is rapidly growing. In recent years, heterozygous somatic mutations in genes encoding epigenetic regulators have been found in all subtypes of myeloid malignancies, supporting the rationale for treatment with epigenetic modifiers...
October 9, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/30304655/classification-and-personalized-prognosis-in-myeloproliferative-neoplasms
#17
MULTICENTER STUDY
Jacob Grinfeld, Jyoti Nangalia, E Joanna Baxter, David C Wedge, Nicos Angelopoulos, Robert Cantrill, Anna L Godfrey, Elli Papaemmanuil, Gunes Gundem, Cathy MacLean, Julia Cook, Laura O'Neil, Sarah O'Meara, Jon W Teague, Adam P Butler, Charlie E Massie, Nicholas Williams, Francesca L Nice, Christen L Andersen, Hans C Hasselbalch, Paola Guglielmelli, Mary F McMullin, Alessandro M Vannucchi, Claire N Harrison, Moritz Gerstung, Anthony R Green, Peter J Campbell
BACKGROUND: Myeloproliferative neoplasms, such as polycythemia vera, essential thrombocythemia, and myelofibrosis, are chronic hematologic cancers with varied progression rates. The genomic characterization of patients with myeloproliferative neoplasms offers the potential for personalized diagnosis, risk stratification, and treatment. METHODS: We sequenced coding exons from 69 myeloid cancer genes in patients with myeloproliferative neoplasms, comprehensively annotating driver mutations and copy-number changes...
October 11, 2018: New England Journal of Medicine
https://www.readbyqxmd.com/read/30302184/non-specific-skin-purpura
#18
S E Shalihin, Z Harun, I F Osman
Essential thrombocythemia is one of the myeloproliferative neoplasms. Palpable purpura is a rare manifestation that may delay diagnosis and treatment. We report a case of essential thrombocythemia in a 50-year-old man, who presented with recurrent thigh pain for the past one year with nonspecific localized purpura. His full blood count revealed isolated thrombocytosis of 880,000/µL with an impression of myeloproliferative disorder from peripheral blood film. He was referred urgently to the hematology team, which proceeded with a venesection...
2018: Malaysian Family Physician
https://www.readbyqxmd.com/read/30295263/-variation-of-stat3-gene-in-myleproliferative-neoplasms-and-its-significance
#19
Mei Tan, Xi Luo, Qiong Su, Cheng-Shuang Huang, Yu-Hang Yang, Ying Rong, Ping Zhu, Yan Chen
OBJECTIVE: To detect the mutation and single nucleotide polymorphisms of STAT3 gene in the patients with myeloproliferative neoplasms (MPN), and to analyze the correlation between STAT3 gene and the subtypes of MPN. METHODS: A total of 147 patients with MPN were selected, including 28 patients with polycythaemia vera (PV), 46 patients with essential thrombocythemia (ET), 10 patients with primary myelofibrosis (PMF), and 63 patients with chronic myeloid leukemia (CML); and 88 healthy persons were used as normal control...
October 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/30275952/srsf2-mutations-in-myelodysplasia-myeloproliferative-neoplasms
#20
REVIEW
Amandeep Aujla, Katherine Linder, Chaitanya Iragavarapu, Michael Karass, Delong Liu
Recurrent gene mutations have been described with varying frequencies in myelodysplasia (MDS) /myeloproliferative neoplasm (MPN) overlap syndromes (MMOS). Recent work has placed significant focus on understanding the role of gene lesions involving the spliceosomal machinery in leukemogeneis. SRSF2 is a gene encoding critical spliceosomal proteins. SRSF2 mutations appear to play an important role in pathogenesis of MMOS, particularly in chronic myelomonocytic leukemia. Inhibition of splicing may be a new therapeutic approach...
2018: Biomarker Research
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