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https://www.readbyqxmd.com/read/28428987/microarray-profiling-and-co-expression-network-analysis-of-the-lncrnas-and-mrnas-associated-with-acute-leukemia-in-adults
#1
Hui Cheng, Chong Mei Huang, Yang Wang, Xiao Xia Hu, Xiao Qian Xu, Xian Min Song, Gu Sheng Tang, Li Chen, Jian Min Yang
Acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) are common types of acute leukemia in adults and cause low survival rate and poor outcome after 5 years despite high rates of complete remission (CR) with modern chemotherapeutic regimens. To understand the distinct mechanisms in leukemogenesis for ALL and AML and to identify markers for diagnosis and treatment, lncRNA and mRNA expression profiles of AML and ALL patients and healthy controls were generated using microarray analysis. For comparison, the differentially expressed mRNA functions were annotated using gene ontology (GO) and pathway analysis...
April 21, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28428897/acute-myeloid-leukemia-with-basophilic-differentiation-transformed-from-myelodysplastic-syndrome
#2
Yasuhiro Tanaka, Atsushi Tanaka, Akiko Hashimoto, Kumiko Hayashi, Isaku Shinzato
Myelodysplastic syndrome (MDS) terminally transforms to acute myeloid leukemia (AML) or bone marrow failure syndrome, but acute myeloid leukemia with basophilic differentiation has been rarely reported. An 81-year-old man was referred to our department for further examination of intermittent fever and normocytic anemia during immunosuppressive treatment. Chromosomal analysis showed additional abnormalities involving chromosome 7. He was diagnosed as having MDS. At the time of diagnosis, basophils had not proliferated in the bone marrow...
2017: Case Reports in Hematology
https://www.readbyqxmd.com/read/28428668/prognostic-parameters-of-acute-myeloid-leukaemia-at-presentation
#3
Azra Jahic, Ermina Iljazovic, Samira Hasic, Aida Custovic Arnautovic, Damir Sabitovic, Semir Mesanovic, Haris Sahovic, Vlastimir Simendic
INTRODUCTION: The treatment response and outcome in acute myeloid leukaemia (AML) is heterogeneous. AIM: To analyze the prognostic parameters of AML at presentation. METHODS: The total sample of 44 AML patients was analyzed on the basis of age <55 and ≥55 years, sex, WBC count <50x10/(9)/l and ≥50x10/(9)/l, the Hb concentration <100 g/l and ≥100 g/l, PLT count <100x10/(9)/l and ≥100x10/(9)/l, Karnofsky score <60% and >60%, cytogenetics, CD56 expression, morphological type and types of treatment (standard and reduced induction chemotherapy, high-dose chemotherapy/stem cell transplantation - autologous and HLA matched, related, allogeneic, together and separately)...
February 2017: Medical Archives
https://www.readbyqxmd.com/read/28428057/natural-killer-cells-differentiated-in-vitro-from-cord-blood-cd34-cells-are-more-advantageous-for-use-as-an-immunotherapy-than-peripheral-blood-and-cord-blood-natural-killer-cells
#4
Anna Domogala, Michael Blundell, Adrian Thrasher, Mark W Lowdell, J Alejandro Madrigal, Aurore Saudemont
BACKGROUND AIMS: Natural killer (NK) cells have the potential to become a successful immunotherapy as they can target malignant cells without being direct effectors of graft-versus-host disease. Our group has previously shown that large numbers of functional NK cells can be differentiated in vitro from umbilical cord blood (CB) CD34(+) cells. To produce a clinically relevant and effective immunotherapy, we hypothesized that it is essential that the NK cells are able to proliferate and persist in vivo while maintaining an optimal activation status and killing capacity...
April 17, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28427597/intentional-percutaneous-laceration-of%C3%A2-the%C3%A2-anterior-mitral-leaflet-to-prevent%C3%A2-outflow%C3%A2-obstruction-during-transcatheter-mitral-valve-replacement-first-in-human%C3%A2-experience
#5
Vasilis C Babaliaros, Adam B Greenbaum, Jaffar M Khan, Toby Rogers, Dee Dee Wang, Marvin H Eng, William W O'Neill, Gaetano Paone, Vinod H Thourani, Stamatios Lerakis, Dennis W Kim, Marcus Y Chen, Robert J Lederman
OBJECTIVES: This study sought to use a new catheter technique to split the anterior mitral valve leaflet (AML) and prevent iatrogenic left ventricular outflow tract (LVOT) obstruction immediately before transcatheter mitral valve replacement (TMVR). BACKGROUND: LVOT obstruction is a life-threatening complication of TMVR, caused by septal displacement of the AML. METHODS: The procedure was used in patients with severe mitral valve disease and prohibitive surgical risk...
April 24, 2017: JACC. Cardiovascular Interventions
https://www.readbyqxmd.com/read/28427227/high-dose-ascorbate-and-arsenic-trioxide-selectively-kill-acute-myeloid-leukemia-and-acute-promyelocytic-leukemia-blasts-in-vitro
#6
Nélida I Noguera, Elvira Pelosi, Daniela F Angelini, Maria Liliana Piredda, Gisella Guerrera, Eleonora Piras, Luca Battistini, Lauretta Massai, Anna Berardi, Gianfranco Catalano, Laura Cicconi, Germana Castelli, Agnese D'Angiò, Luca Pasquini, Grazia Graziani, Giuseppe Fioritoni, Maria Teresa Voso, Domenico Mastrangelo, Ugo Testa, Francesco Lo-Coco
The use of high-dose ascorbate (ASC) for the treatment of human cancer has been attempted several decades ago and has been recently revived by several in vitro and in vivo studies in solid tumors. We tested the cytotoxic effects of ASC, alone or in combination with arsenic trioxide (ATO) in acute myeloid leukemia (AML) and acute promyelocytic leukemia (APL). Leukemic cell lines and primary blasts from AML and APL patients were treated with graded concentrations of ASC, alone or in association with standard concentration (1 μM) of ATO...
March 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422713/sel120-34a-is-a-novel-cdk8-inhibitor-active-in-aml-cells-with-high-levels-of-serine-phosphorylation-of-stat1-and-stat5-transactivation-domains
#7
Tomasz Rzymski, Michał Mikula, Eliza Żyłkiewicz, Agnieszka Dreas, Katarzyna Wiklik, Aniela Gołas, Katarzyna Wójcik, Magdalena Masiejczyk, Anna Wróbel, Izabela Dolata, Agata Kitlińska, Małgorzata Statkiewicz, Urszula Kuklinska, Krzysztof Goryca, Łukasz Sapała, Aleksandra Grochowska, Aleksandra Cabaj, Małgorzata Szajewska-Skuta, Ewelina Gabor-Worwa, Katarzyna Kucwaj, Arkadiusz Białas, Adam Radzimierski, Michał Combik, Jakub Woyciechowski, Maciej Mikulski, Renata Windak, Jerzy Ostrowski, Krzysztof Brzózka
Inhibition of oncogenic transcriptional programs is a promising therapeutic strategy. A substituted tricyclic benzimidazole, SEL120-34A, is a novel inhibitor of Cyclin-dependent kinase 8 (CDK8), which regulates transcription by associating with the Mediator complex. X-ray crystallography has shown SEL120-34A to be a type I inhibitor forming halogen bonds with the protein's hinge region and hydrophobic complementarities within its front pocket. SEL120-34A inhibits phosphorylation of STAT1 S727 and STAT5 S726 in cancer cells in vitro...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422420/a-study-of-disseminated-intravascular-coagulation-in-acute-leukemia-reveals-markedly-elevated-d-dimer-levels-are-a-sensitive-indicator-of-acute-promyelocytic-leukemia
#8
N Shahmarvand, J S Oak, M J Cascio, M Alcasid, E Goodman, B C Medeiros, D A Arber, J L Zehnder, R S Ohgami
INTRODUCTION: While the presence of disseminated intravascular coagulation (DIC) has been implicated in worse clinical outcome in acute leukemia, the relationship between different subtypes of acute leukemia and the clinicopathologic features of DIC has not been systematically well studied. METHODS: In this study, we retrospectively reviewed 149 cases of newly diagnosed acute leukemia and assessed the utility of evaluating red blood cell morphologic features, and coagulation parameters in determining the presence of DIC as well as differentiating subtypes of acute leukemia...
April 19, 2017: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/28421420/the-future-of-targeting-flt3-activation-in-aml
#9
REVIEW
Mark B Leick, Mark J Levis
Internal tandem duplications (ITD) and tyrosine-kinase domain (TKD) mutations of the FMS-like tyrosine-kinase 3 (FLT3) can be found in up to one third of patients with acute myeloid leukemia (AML) and confer a poor prognosis. First discovered 20 years ago, these mutations were identified as viable therapeutic targets, and FLT3 tyrosine-kinase inhibitors (TKIs) have been in development for the last decade with steadily increasing potency. However, FLT3-mutated AML often acquires resistance to the growing armamentarium of FLT3 inhibitors through a variety of mechanisms...
April 18, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28420723/mitochondrial-bax-determines-the-predisposition-to-apoptosis-in-human-aml
#10
Frank Reichenbach, Cornelius Wiedenmann, Enrico Schalk, Diana Becker, Kathrin Funk, Peter Scholz-Kreisel, Franziska Todt, Denise Wolleschak, Konstanze Dohner, Jens U Marquardt, Florian Heidel, Frank Edlich
Purpose: Cell-to-cell variability in apoptosis signaling contributes to heterogenic responses to cytotoxic stress in clinically heterogeneous neoplasia, such as acute myeloid leukemia (AML). The BCL-2 proteins BAX and BAK can commit mammalian cells to apoptosis and are inhibited by retrotranslocation from the mitochondria into the cytosol. The subcellular localization of BAX and BAK could determine the cellular predisposition to apoptotic death. Experimental design: The relative localization of BAX and BAK was determined by fractionation of AML cell lines and patient samples of a test cohort and a validation cohort...
April 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28420416/emerging-therapies-for-acute-myeloid-leukemia
#11
REVIEW
Caner Saygin, Hetty E Carraway
Acute myeloid leukemia (AML) is characterized by clinical and biological heterogeneity. Despite the advances in our understanding of its pathobiology, the chemotherapy-directed management has remained largely unchanged in the past 40 years. However, various novel agents have demonstrated clinical activity, either as single agents (e.g., isocitrate dehydrogenase (IDH) inhibitors, vadastuximab) or in combination with standard induction/consolidation at diagnosis and with salvage regimens at relapse. The classes of agents described in this review include novel cytotoxic chemotherapies (CPX-351 and vosaroxin), epigenetic modifiers (guadecitabine, IDH inhibitors, histone deacetylase (HDAC) inhibitors, bromodomain and extraterminal (BET) inhibitors), FMS-like tyrosine kinase receptor 3 (FLT3) inhibitors, and antibody-drug conjugates (vadastuximab), as well as cell cycle inhibitors (volasertib), B-cell lymphoma 2 (BCL-2) inhibitors, and aminopeptidase inhibitors...
April 18, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28420120/clinical-outcomes-of-217-patients-with-acute-erythroleukemia-according-to-treatment-type-and-line-a-retrospective-multinational-study
#12
Antonio M Almeida, Thomas Prebet, Raphael Itzykson, Fernando Ramos, Haifa Al-Ali, Jamile Shammo, Ricardo Pinto, Luca Maurillo, Jaime Wetzel, Pellegrino Musto, Arjan A Van De Loosdrecht, Maria Joao Costa, Susana Esteves, Sonja Burgstaller, Reinhard Stauder, Eva M Autzinger, Alois Lang, Peter Krippl, Dietmar Geissler, Jose Francisco Falantes, Carmen Pedro, Joan Bargay, Guillermo Deben, Ana Garrido, Santiago Bonanad, Maria Diez-Campelo, Sylvain Thepot, Lionel Ades, Wolfgang R Sperr, Peter Valent, Pierre Fenaux, Mikkael A Sekeres, Richard Greil, Lisa Pleyer
Acute erythroleukemia (AEL) is a rare disease typically associated with a poor prognosis. The median survival ranges between 3-9 months from initial diagnosis. Hypomethylating agents (HMAs) have been shown to prolong survival in patients with myelodysplastic syndromes (MDS) and AML, but there is limited data of their efficacy in AEL. We collected data from 210 AEL patients treated at 28 international sites. Overall survival (OS) and PFS were estimated using the Kaplan-Meier method and the log-rank test was used for subgroup comparisons...
April 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28420034/a-fluorescence-in-situ-hybridization-based-screen-allows-rapid-detection-of-adverse-cytogenetic-alterations-in-patients-with-acute-myeloid-leukemia
#13
Nadine Sandhöfer, Klaus H Metzeler, Purvi M Kakadia, Zlatana Pasalic, Wolfgang Hiddemann, Michaela Neusser, Ortrud Steinlein, Michael Fiegl, Marion Subklewe, Karsten Spiekermann, Stefan K Bohlander, Stephanie Schneider, Jan Braess
In adult acute myeloid leukemia (AML), the karyotype of the leukemic cell is among the strongest prognostic factors. The Medical Research Council (MRC) and the European LeukemiaNet (ELN) classifications distinguish between favorable, intermediate and adverse cytogenetic risk patients who differ in their treatment response and overall survival. Conventional cytogenetic analyses are a mandatory component of AML diagnostics but they are time-consuming; therefore, therapeutic decisions in elderly patients are often delayed...
April 18, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28419965/chidamide-in-flt3-itd-positive-acute-myeloid-leukemia-and-the-synergistic-effect-in-combination-with-cytarabine
#14
Xia Li, Xiao Yan, Wenjian Guo, Xin Huang, Jiansong Huang, Mengxia Yu, Zhixin Ma, Yu Xu, ShuJuan Huang, Chenying Li, Yile Zhou, Jie Jin
Chidamide, a novel histone deacetylase inhibitor (HDACi), has been approved for treatment of T-cell lymphomas in multiple clinical trials. It has been demonstrated that chidamide can inhibit cell cycle, promote apoptosis and induce differentiation in leukemia cells, whereas its effect on acute myeloid leukemia (AML) patients with FLT3-ITD mutation has not been clarified. In this study, we found that chidamide specifically induced G0/G1 arrest and apoptosis in FLT3-ITD positive AML cells in a concentration and time-dependent manner...
April 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28419882/novel-homozygous-fancl-mutation-and-somatic-heterozygous-setbp1-mutation-in-a-chinese-girl-with-fanconi-anemia
#15
Weiqing Wu, Yang Liu, Qinghua Zhou, Qin Wang, Fuwei Luo, Zhiyong Xu, Qian Geng, Peining Li, Hui Z Zhang, Jiansheng Xie
Fanconi Anemia (FA) is a rare genetically heterogeneous disorder with 17 known complement groups caused by mutations in different genes. FA complementation group L (FA-L, OMIM #608111) occurred in 0.2% of all FA and only eight mutant variants in the FANCL gene were documented. Phenotype and genotype correlation in FANCL associated FA is still obscure. Here we describe a Chinese girl with FA-L caused by a novel homozygous mutation c.822_823insCTTTCAGG (p.Asp275LeufsX13) in the FANCL gene. The patient's clinical course was typical for FA with progression to bone marrow failure, and death from acute myelomonocytic leukemia (AML-M4) at 9 years of age...
April 15, 2017: European Journal of Medical Genetics
https://www.readbyqxmd.com/read/28419422/early-mortality-and-complications-in-hospitalized-adult-californians-with-acute-myeloid-leukaemia
#16
Gwendolyn Ho, Brian A Jonas, Qian Li, Ann Brunson, Ted Wun, Theresa H M Keegan
Few studies have evaluated the impact of complications, sociodemographic and clinical factors on early mortality (death ≤60 days from diagnosis) in acute myeloid leukaemia (AML) patients. Using data from the California Cancer Registry linked to hospital discharge records from 1999 to 2012, we identified patients aged ≥15 years with AML who received inpatient treatment (N = 6359). Multivariate logistic regression analyses were used to assess the association of complications with early mortality, adjusting for sociodemographic factors, comorbidities and hospital type...
April 17, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28418922/novel-impact-of-the-dnmt3a-r882h-mutation-on-gsh-metabolism-in-a-k562-cell-model-established-by-talens
#17
Li Yang, Ya'Nan Liu, Na Zhang, Xiao'Yi Ding, Wei Zhang, Ke'Feng Shen, Liang Huang, Jian'Feng Zhou, Sen Cui, Zun'Min Zhu, Zheng Hu, Min Xiao
DNA methyltransferase 3A (DNMT3A) mutations occurred in 18%~23% of acute myeloid leukemia (AML) patients, and were considered to be an adverse prognostic factor for adult de novo AML cases. However, the relevant molecular mechanism of the mutation in AML pathogenesis remains obscure. In this study, we established K562 and SKM1 cell model carrying the DNMT3A R882H mutation via transcription activator-like effector nuclease (TALEN) and Clustered regularly interspaced short palindromic repeats (CRISPR/Cas9) technology, and discovered that mutated DNMT3A could promote the proliferative capability of malignant cell clones...
March 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28418873/combined-inhibition-of-gli-and-flt3-signaling-leads-to-effective-anti-leukemic-effects-in-human-acute-myeloid-leukemia
#18
Emily-Marie Latuske, Hauke Stamm, Marianne Klokow, Gabi Vohwinkel, Jana Muschhammer, Carsten Bokemeyer, Manfred Jücker, Maxim Kebenko, Walter Fiedler, Jasmin Wellbrock
Activation of the Hedgehog pathway has been implicated in the pathogenesis of several tumor types including myeloid leukemia. Previously we demonstrated that overexpression of Hedgehog downstream mediators GLI1/2 confers an adverse prognosis to patients with acute myeloid leukemia (AML) and is correlated with a FLT3 mutated status. To analyze a possible non-canonical activation of the Hedgehog pathway via FLT3 and PI3K, we performed blocking experiments utilizing inhibitors for FLT3 (sunitinib), PI3K (PF-04691502) and GLI1/2 (GANT61) in FLT3-mutated and FLT3 wildtype AML cell lines and primary blasts...
March 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28418085/puquitinib-a-novel-orally-available-pi3k%C3%AE-inhibitor-exhibits-potent-antitumor-efficacy-against-acute-myeloid-leukemia
#19
Chengying Xie, Ye He, Mingyue Zhen, Yulan Wang, Yongping Xu, Liguang Lou
The PI3Kδ isoform (PIK3CD), also known as P110δ, is predominately expressed in leukocytes and has been implicated as a potential target in the treatment of hematological malignancies. In this report, we detailed the pharmacologic properties of puquitinib, a novel, orally available PI3Kδ inhibitor. Puquitinib, which binds to the ATP-binding pocket of PI3Kδ, was highly selective and potent for PI3Kδ relative to other PI3K I isoforms and a panel of protein kinases, exhibiting low-nanomolar biochemical and cellular inhibitory potencies...
April 18, 2017: Cancer Science
https://www.readbyqxmd.com/read/28416751/proteasome-inhibition-enhances-the-efficacy-of-volasertib-induced-mitotic-arrest-in-aml-in-vitro-and-prolongs-survival-in-vivo
#20
Dominik Schnerch, Julia Schüler, Marie Follo, Julia Felthaus, Dagmar Wider, Kathrin Klingner, Christine Greil, Justus Duyster, Monika Engelhardt, Ralph Wäsch
Elderly and frail patients, diagnosed with acute myeloid leukemia (AML) and ineligible to undergo intensive treatment, have a dismal prognosis. The small molecule inhibitor volasertib induces a mitotic block via inhibition of polo-like kinase 1 and has shown remarkable anti-leukemic activity when combined with low-dose cytarabine. We have demonstrated that AML cells are highly vulnerable to cell death in mitosis yet manage to escape a mitotic block through mitotic slippage by sustained proteasome-dependent slow degradation of cyclin B...
March 28, 2017: Oncotarget
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