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leukemia myelomonocytic

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https://www.readbyqxmd.com/read/29322838/chronic-myelomonocytic-leukemia-with-central-nervous-system-involvement
#1
Michelle Hannon, Lindsay Wilde, Nneamaka Nwaoduah, Margaret Kasner
No abstract text is available yet for this article.
January 11, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29318596/idiopathic-chilblains-in-myelomonocytic-leukemia-not-a-simple-association
#2
Gianluca Nazzaro, Giovanni Genovese, Angelo V Marzano
No abstract text is available yet for this article.
January 10, 2018: International Journal of Dermatology
https://www.readbyqxmd.com/read/29316027/somatic-mutations-activating-wiskott-aldrich-syndrome-protein-concomitant-with-ras-pathway-mutations-in-juvenile-myelomonocytic-leukemia-patients
#3
A Coppe, L Nogara, M S Pizzuto, A Cani, S Cesaro, R Masetti, F Locatelli, G Te Kronnie, G Basso, S Bortoluzzi, S Bresolin
The WAS gene product is expressed exclusively in the cytoplasm of hematopoietic cells and constitutional genetic abrogation of WASP leads to Wiskott-Aldrich syndrome (WAS). Moreover, mutational activation of WASP has been associated with X-linked neutropenia (XLN). Although studies reported that patients with constitutional WAS mutations affecting functional WASP expression may present Juvenile MyeloMonocytic Lukemia (JMML)-like features, confounding differential diagnosis above all in the co-presence of mutated RAS, an activating somatic mutation of WASP has not been previously described in JMML patients...
January 7, 2018: Human Mutation
https://www.readbyqxmd.com/read/29310473/a-new-approach-for-diagnosing-chronic-myelomonocytic-leukemia-using-structural-parameters-of-sysmex-xntm-analyzers-in-routine-laboratory-practice
#4
Françoise Schillinger, Elise Sourdeau, Marouane Boubaya, Lucile Baseggio, Sylvain Clauser, Edouard Cornet, Camille Debord, Jean-Pierre Defour, Frédérique Dubois, Marion Eveillard, Anne-Cécile Galoisy, Marie-Odile Geay, François Mullier, Vanessa Nivaggioni, Valérie Soenen, Pascal Morel, Francine Garnache-Ottou, Emily Ronez, Valérie Bardet, Eric Deconinck
According to WHO recommendations, diagnosis of chronic myelomonocytic leukemia (CMML) beforehand requires microscopic examination of peripheral blood to identify dysplasia and/or blasts when monocytes are greater or equal to 1.0 × 109/L and 10% of leucocytes. We analyzed parameters derived from SysmexTM XN analyzers to improve the management of microscopic examination for monocytosis. We analyzed results of the complete blood count and the positioning and dispersion parameters of polymorphonuclear neutrophils and monocytes in 61 patients presenting with CMML and 635 control patients presenting with a reactive monocytosis...
January 8, 2018: Scandinavian Journal of Clinical and Laboratory Investigation
https://www.readbyqxmd.com/read/29296739/engraftment-of-chronic-myelomonocytic-leukemia-cells-in-immunocompromised-mice-supports-disease-dependency-on-cytokines
#5
Yanyan Zhang, Liang He, Dorothée Selimoglu-Buet, Chloe Jego, Margot Morabito, Christophe Willekens, M'boyba Khadija Diop, Patrick Gonin, Valérie Lapierre, Nathalie Droin, Eric Solary, Fawzia Louache
Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell disorder that typically associates with mutations in epigenetic, splicing, and signaling genes. Genetically modified mouse models only partially recapitulate the disease phenotype, whereas xenotransplantation of CMML cells in immunocompromised mice has been rarely successful so far. Here, CMML CD34+ cells sorted from patient bone marrow (BM) or peripheral blood (PB) were injected intravenously into NSG (NOD/LtSz-scid IL2rγnull) mice and NSG mice engineered to express human granulo-monocyte colony-stimulating factor, stem cell factor, and interleukin-3 (NSGS mice)...
June 13, 2017: Blood Advances
https://www.readbyqxmd.com/read/29288910/3q26-evi1-rearrangement-in-myelodysplastic-myeloproliferative-neoplasms-an-early-event-associated-with-a-poor-prognosis
#6
Zhihong Hu, Shimin Hu, Changsheng Ji, Zhenya Tang, Beenu Thakral, Sanam Loghavi, L Jeffrey Medeiros, Wei Wang
3q26.2/EVI1 rearrangements resulting in EVI1 overexpression play an important role in leukemogenesis and are associated with treatment resistance and a poorer prognosis in patients with acute myeloid leukemia, myelodysplastic syndrome, chronic myeloid leukemia and BCR-ABL negative myeloproliferative neoplasms. In this study, we aim to explore the clinicopathological features of myelodysplastic/myeloproliferative (MDS/MPN) neoplasms with 3q26.2/EVI1 rearrangements and determine the potential impact of these cytogenetic abnormalities on treatment response and survival...
December 23, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29280197/fulminant-cryptococcus-neoformans-infection-with-fatal-pericardial-tamponade-in-a-patient-with-chronic-myelomonocytic-leukemia-who-was-treated-with-ruxolitinib-case-report-and-review-of-fungal-pericarditis
#7
Jing Liu, Elie Mouhayar, Jeffrey J Tarrand, Dimitrios P Kontoyiannis
Cryptococcus neoformans is a saprophytic fungal pathogen that can cause serious illness in immune-compromised hosts and it presents with a wide variety of clinical symptoms. We present a fatal case of fulminant C. neoformans infection presenting as pericardial tamponade in a 71-year-old male with chronic myelomonocytic leukemia undergoing chemotherapy with the JAK-STAT inhibitor ruxolitinib. We also review the published cases of fungal pericarditis/tamponade. In addition to illustrating an atypical presentation of C...
December 27, 2017: Mycoses
https://www.readbyqxmd.com/read/29279013/novel-approaches-to-diagnosis-and-treatment-of-juvenile-myelomonocytic-leukemia
#8
Franco Locatelli, Mattia Algeri, Pietro Merli, Luisa Strocchio
Juvenile myelomonocytic leukemia (JMML) is a clonal hematopoietic disorder of infancy/early childhood, resulting from oncogenic mutations in genes involved in the Ras pathway. As JMML often exhibits an aggressive course, the timing of diagnosis and treatment is critical to outcome. Areas covered: This review summarizes current approaches to diagnosis and treatment of JMML, highlighting most recent insights into genetic and epigenetic mechanisms underlying the disease, and providing an overview of novel potential therapeutic strategies...
January 3, 2018: Expert Review of Hematology
https://www.readbyqxmd.com/read/29275866/cooperative-epigenetic-remodeling-by-tet2-loss-and-nras-mutation-drives-myeloid-transformation-and-mek-inhibitor-sensitivity
#9
Hiroyoshi Kunimoto, Cem Meydan, Abbas Nazir, Justin Whitfield, Kaitlyn Shank, Franck Rapaport, Rebecca Maher, Elodie Pronier, Sara C Meyer, Francine E Garrett-Bakelman, Martin Tallman, Ari Melnick, Ross L Levine, Alan H Shih
Mutations in epigenetic modifiers and signaling factors often co-occur in myeloid malignancies, including TET2 and NRAS mutations. Concurrent Tet2 loss and NrasG12D expression in hematopoietic cells induced myeloid transformation, with a fully penetrant, lethal chronic myelomonocytic leukemia (CMML), which was serially transplantable. Tet2 loss and Nras mutation cooperatively led to decrease in negative regulators of mitogen-activated protein kinase (MAPK) activation, including Spry2, thereby causing synergistic activation of MAPK signaling by epigenetic silencing...
December 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29274396/transplant-conditioning-with-treosulfan-fludarabine-with-or-without-tbi-a-randomized-phase-ii-trial-in-patients-with-mds-and-aml
#10
H Joachim Deeg, Emily A Stevens, Rachel B Salit, Ralph P Ermoian, Min Fang, Boglarka Gyurkocza, Mohamed L Sorror, Giancarlo Fatobene, Joachim Baumgart, Lauri M Burroughs, Colleen Delaney, Kris Doney, Daniel N Egan, Mary E D Flowers, Filippo Milano, Jerry P Radich, Bart L Scott, Eileen J Sickle, Brent L Wood, Cecilia Yeung, Barry E Storer
In this prospective randomized phase II "pick the winner" trial we assessed the efficacy of transplant conditioning with treosulfan/fludarabine ± 2 Gy total body irradiation (TBI) in reducing post-transplant relapse in 100 patients, 2-70 (median 57) years of age, with myelodysplastic syndrome/chronic myelomonocytic leukemia (MDS/CMML; n=51) or acute myeloid leukemia (AML; n=49). Patients received intravenous (IV) treosulfan, 14 g/m2/day on days -6 to -4 and IV fludarabine, 30 mg/m2/day on days -6 to -2, alone or combined with 2 Gy TBI (day 0)...
December 20, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29273914/myeloid-neoplasms-with-t-12-22-p13-q12-mn1-evt6-a-systematic-review-of-12-cases
#11
Haigang Shao, Jiannong Cen, Suning Chen, Huiying Qiu, Jinlan Pan
t(12;22)(p13;q12) is a rare but recurrent chromosomal abnormality involving the ETS transcription factor ETV6 and meningioma 1 (MN1) genes. In this study, we analyzed the clinical, cytogenetic, and molecular features of five new patients with the t(12;22)/MN1-EVT6 who presented with acute myeloid leukemia or chronic myelomonocytic leukemia. We subsequently reviewed the literature and identified seven additional cases reported with t(12;22)/MN1-EVT6. Our data suggest that neoplasms carrying the t(12;22)/MN1-ETV6, although rare, can commonly present as myeloid neoplasms at the initial diagnosis, including acute myeloid leukemia (n = 8), myelodysplastic syndrome (n = 2), and myelodysplastic/myeloproliferative neoplasms (n = 2)...
December 22, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/29259247/ras-pathway-mutation-patterns-define-epigenetic-subclasses-in-juvenile-myelomonocytic-leukemia
#12
Daniel B Lipka, Tania Witte, Reka Toth, Jing Yang, Manuel Wiesenfarth, Peter Nöllke, Alexandra Fischer, David Brocks, Zuguang Gu, Jeongbin Park, Brigitte Strahm, Marcin Wlodarski, Ayami Yoshimi, Rainer Claus, Michael Lübbert, Hauke Busch, Melanie Boerries, Mark Hartmann, Maximilian Schönung, Umut Kilik, Jens Langstein, Justyna A Wierzbinska, Caroline Pabst, Swati Garg, Albert Catalá, Barbara De Moerloose, Michael Dworzak, Henrik Hasle, Franco Locatelli, Riccardo Masetti, Markus Schmugge, Owen Smith, Jan Stary, Marek Ussowicz, Marry M van den Heuvel-Eibrink, Yassen Assenov, Matthias Schlesner, Charlotte Niemeyer, Christian Flotho, Christoph Plass
Juvenile myelomonocytic leukemia (JMML) is an aggressive myeloproliferative disorder of early childhood characterized by mutations activating RAS signaling. Established clinical and genetic markers fail to fully recapitulate the clinical and biological heterogeneity of this disease. Here we report DNA methylome analysis and mutation profiling of 167 JMML samples. We identify three JMML subgroups with unique molecular and clinical characteristics. The high methylation group (HM) is characterized by somatic PTPN11 mutations and poor clinical outcome...
December 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/29259179/genome-wide-dna-methylation-is-predictive-of-outcome-in-juvenile-myelomonocytic-leukemia
#13
Elliot Stieglitz, Tali Mazor, Adam B Olshen, Huimin Geng, Laura C Gelston, Jon Akutagawa, Daniel B Lipka, Christoph Plass, Christian Flotho, Farid F Chehab, Benjamin S Braun, Joseph F Costello, Mignon L Loh
Juvenile myelomonocytic leukemia (JMML) is a myeloproliferative disorder of childhood caused by mutations in the Ras pathway. Outcomes in JMML vary markedly from spontaneous resolution to rapid relapse after hematopoietic stem cell transplantation. Here, we hypothesized that DNA methylation patterns would help predict disease outcome and therefore performed genome-wide DNA methylation profiling in a cohort of 39 patients. Unsupervised hierarchical clustering identifies three clusters of patients. Importantly, these clusters differ significantly in terms of 4-year event-free survival, with the lowest methylation cluster having the highest rates of survival...
December 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/29249821/aza-ms-a-novel-multiparameter-mass-spectrometry-method-to-determine-the-intracellular-dynamics-of-azacitidine-therapy-in-vivo
#14
A Unnikrishnan, A V N Quynh, R Pickford, M J Raftery, A C Nunez, A Verma, L B Hesson, J E Pimanda
The cytidine analogue, 5-azacytidine (AZA; 5-AZA-cR), is the primary treatment for myelodysplastic syndrome and chronic myelomonocytic leukaemia. However, only ~50% of treated patients will respond to AZA and the drivers of AZA resistance in vivo are poorly understood. To better understand the intracellular dynamics of AZA upon therapy and decipher the molecular basis for AZA resistance, we have developed a novel, multiparameter, quantitative mass spectrometry method (AZA-MS). Using AZA-MS, we have accurately quantified the abundance of the ribonucleoside (5-AZA-cR) and deoxyribonucleoside (5-AZA-CdR) forms of AZA in RNA, DNA and the cytoplasm within the same sample using nanogram quantities of input material...
December 18, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29227812/overexpression-of-arginase-1-is-linked-to-dnmt3a-and-tet2-mutations-in-lower-grade-myelodysplastic-syndromes-and-chronic-myelomonocytic-leukemia
#15
A H Cull, D Mahendru, B Snetsinger, D Good, K Tyryshkin, A Chesney, Z Ghorab, M Reis, R Buckstein, R A Wells, M J Rauh
Immune dysregulation is a common feature of myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML), particularly in early stages. However, the genetic basis remains poorly understood. We recently reported that macrophages from mice deficient in tet methylcytosine dioxygenase 2 (Tet2), a model of MDS/CMML, are hyperinflammatory and have increased expression of arginase 1 (Arg1). In macrophages and myeloid derived suppressor cells (MDSCs) expression of Arg1 contributes to T-cell suppression and immune evasion by L-arginine depletion, in the setting of chronic inflammation and cancer...
December 6, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29226275/presentation-of-gallbladder-chloroma-in-b-mode-imaging-and-contrast-enhanced-ultrasound-ceus-in-a-patient-with-acute-myelomonocytic-leukemia-aml-m5
#16
Corinna Trenker, Marius Dohse, StephanK Metzelder, Anette Ramaswamy, Walter Hundt, Christian Görg
No abstract text is available yet for this article.
September 2017: Ultrasound International Open
https://www.readbyqxmd.com/read/29225884/setbp1-mutations-as-a-biomarker-for-myelodysplasia-myeloproliferative-neoplasm-overlap-syndrome
#17
REVIEW
Katherine Linder, Chaitanya Iragavarapu, Delong Liu
Myelodysplasia (MDS) /myeloproliferative neoplasm (MPN) overlap syndrome has been described since the 2001 WHO classification as disorders that have both proliferative and dysplastic changes simultaneously. Specific disorders include chronic myelomonocytic leukemia (CMML), juvenile myelomonocytic leukemia (JMML), BCR-ABL negative atypical chronic myeloid leukemia (aCML) and unclassifiable MDS/MPN (MPN/MDS-U). Recurrent gene mutations in these conditions have been described. Among them, SETBP1 mutations have been identified in up to 32% of aCML, 24% of JMML, 18% of CMML and 10% of MDS/MPN-U patients...
2017: Biomarker Research
https://www.readbyqxmd.com/read/29196081/prognostic-impact-of-donor-source-on-allogeneic-hematopoietic-stem-cell-transplantation-outcomes-in-adults-with-chronic-myelomonocytic-leukemia-a-nationwide-retrospective-analysis-in-japan
#18
Hidehiro Itonaga, Kazunari Aoki, Jun Aoki, Takayuki Ishikawa, Ken Ishiyama, Naoyuki Uchida, Toru Sakura, Kazuteru Ohashi, Mineo Kurokawa, Yukiyasu Ozawa, Ken-Ichi Matsuoka, Yukinori Nakamura, Fumihiko Kimura, Koji Iwato, Yuichiro Nawa, Makoto Hirokawa, Koji Kato, Tatsuo Ichinohe, Yoshiko Atsuta, Yasushi Miyazaki
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative therapeutic option for chronic myelomonocytic leukemia (CMML). We retrospectively compared the post-transplant outcomes of 159 CMML patients who received allo-HSCT using 4 types of donor sources: human leukocyte antigen (HLA)-matched related donor grafts, unrelated bone marrow, unrelated cord blood, and HLA-mismatched related donor grafts. The median patient age at allo-HSCT was 54 years (range, 16 -75 years). In multivariate analyses, the use of HLA-matched related donor grafts correlated with better OS than unrelated bone marrow (hazard ratio [HR], 2...
November 28, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29192651/myeloid-neoplasms-with-features-intermediate-between-primary-myelofibrosis-and-chronic-myelomonocytic-leukemia
#19
Jennifer Chapman, Julia T Geyer, Mahsa Khanlari, Adrienne Moul, Carmen Casas, Scot T Connor, Yao-Shan Fan, Justin M Watts, Ronan T Swords, Francisco Vega, Attilio Orazi
Monocytosis can develop during disease course in primary myelofibrosis simulating that seen in chronic myelomonocytic leukemia, and should not lead to disease reclassification. In contrast, at presentation, rare cases have clinical, morphologic, and molecular genetic features truly intermediate between primary myelofibrosis and chronic myelomonocytic leukemia. The taxonomy and natural history of these diseases are unclear. We identified cases which either: (1) fulfilled the 2008 World Health Organization criteria for primary myelofibrosis but had absolute monocytosis and, when available, chronic myelomonocytic leukemia-related mutations (ASXL1, SRSF2, TET2) or (2) fulfilled criteria of chronic myelomonocytic leukemia but had megakaryocytic proliferation and atypia, marrow fibrosis, and myeloproliferative-type driver mutations (JAK2, MPL, CALR)...
December 1, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29160764/dna-methylation-profile-in-chronic-myelomonocytic-leukemia-associates-with-distinct-clinical-biological-and-genetic-features
#20
Laura Palomo, Roberto Malinverni, Marta Cabezón, Blanca Xicoy, Montserrat Arnan, Rosa Coll, Helena Pomares, Olga García, Francisco Fuster-Tormo, Javier Grau, Evarist Feliu, Francesc Solé, Marcus Buschbeck, Lurdes Zamora
Chromosomal abnormalities are detected in 20-30% of patients with chronic myelomonocytic leukemia (CMML) and correlate with prognosis. On the mutation level, disruptive alterations are particularly frequent in chromatin regulatory genes. However, little is known about the consequential alterations in the epigenetic marking of the genome. Here, we report the analysis of genomic DNA methylation patterns of 64 CMML patients and 10 healthy controls, using a DNA methylation microarray focused on promoter regions...
November 21, 2017: Epigenetics: Official Journal of the DNA Methylation Society
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