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acute leukaemia

Adam Gassas, Ponni Sivaprakasam, Michelle Cummins, Patricia Breslin, Katharine Patrick, Mary Slatter, Roderick Skinner, Geof Shenton, Brenda Gibson, Sarah Lawson, Toni Petterson, Michael Potter, Beki James, Rachael Hough, Prashant Hiwarkar, Ajay Vora, Paul Veys, Josu De La Fuente, Robert Wynn, Persis Amrolia
Paediatric therapy-related acute myeloid leukaemia (t-AML) is rare and the outcome is poor. While allogeneic haematopoietic stem cell transplantation (HSCT) is generally the accepted modality of treatment, data regarding salvage chemotherapy, remission induction, conditioning regimens, transplant-related mortality and outcome is scarce. Between 2000 and2016, 36 children with t-AML were treated in seven UK paediatric HSCT centres. The most common salvage protocol for remission induction was FLAG with or without idarubicin and 28 patients were in complete morphological remission prior to BMT...
March 15, 2018: Bone Marrow Transplantation
Hetal Patel, Manikandan Periyasamy, Georgina P Sava, Alexander Bondke, Brian W Slafer, Sebastian H B Kroll, Marion Barbazanges, Richard Starkey, Silvia Ottaviani, Alison Harrod, Eric O Aboagye, Laki Buluwela, Matthew J Fuchter, Anthony G M Barrett, Charles Coombes, Simak Ali
Recent reports indicate that some cancer types are especially sensitive to transcription inhibition, suggesting that targeting the transcriptional machinery provides new approaches to cancer treatment. Cyclin-dependent kinase (CDK)7 is necessary for transcription, and acts by phosphorylating the C-terminal domain (CTD) of RNA polymerase II (PolII) to enable transcription initiation. CDK7 additionally regulates the activities of a number of transcription factors, including Estrogen receptor-α (ER). Here we describe a new, orally bioavailable CDK7 inhibitor, ICEC0942...
March 15, 2018: Molecular Cancer Therapeutics
Fabiën N Belle, Juliane Wenke-Zobler, Eva Cignacco, Ben D Spycher, Roland A Ammann, Claudia E Kuehni, Karin Zimmermann
BACKGROUND: Childhood cancer patients (CCP) have been reported to be at increased risk of becoming overweight during treatment. We assessed prevalence of overweight in CCP at diagnosis and at the end of treatment, determined risk factors, and identified weight change during treatment by type of cancer. METHODS: In a multicentre cohort study, we collected height and weight measurements of CCP at diagnosis and repeatedly during treatment. We calculated age- and sex-adjusted BMI Z-scores using references of the International Obesity Taskforce for children...
March 2, 2018: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
M A Alsalem, A A Zaidan, B B Zaidan, M Hashim, H T Madhloom, N D Azeez, S Alsyisuf
CONTEXT: Acute leukaemia diagnosis is a field requiring automated solutions, tools and methods and the ability to facilitate early detection and even prediction. Many studies have focused on the automatic detection and classification of acute leukaemia and their subtypes to promote enable highly accurate diagnosis. OBJECTIVE: This study aimed to review and analyse literature related to the detection and classification of acute leukaemia. The factors that were considered to improve understanding on the field's various contextual aspects in published studies and characteristics were motivation, open challenges that confronted researchers and recommendations presented to researchers to enhance this vital research area...
May 2018: Computer Methods and Programs in Biomedicine
A J Ullmann, J M Aguado, S Arikan-Akdagli, D W Denning, A H Groll, K Lagrou, C Lass-Flörl, R E Lewis, P Munoz, P E Verweij, A Warris, F Ader, M Akova, M C Arendrup, R A Barnes, C Beigelman-Aubry, S Blot, E Bouza, R J M Brüggemann, D Buchheidt, J Cadranel, E Castagnola, A Chakrabarti, M Cuenca-Estrella, G Dimopoulos, J Fortun, J-P Gangneux, J Garbino, W J Heinz, R Herbrecht, C P Heussel, C C Kibbler, N Klimko, B J Kullberg, C Lange, T Lehrnbecher, J Löffler, O Lortholary, J Maertens, O Marchetti, J F Meis, L Pagano, P Ribaud, M Richardson, E Roilides, M Ruhnke, M Sanguinetti, D C Sheppard, J Sinkó, A Skiada, M J G T Vehreschild, C Viscoli, O A Cornely
The European Society for Clinical Microbiology and Infectious Diseases, the European Confederation of Medical Mycology and the European Respiratory Society Joint Clinical Guidelines focus on diagnosis and management of aspergillosis. Of the numerous recommendations, a few are summarized here. Chest computed tomography as well as bronchoscopy with bronchoalveolar lavage (BAL) in patients with suspicion of pulmonary invasive aspergillosis (IA) are strongly recommended. For diagnosis, direct microscopy, preferably using optical brighteners, histopathology and culture are strongly recommended...
March 12, 2018: Clinical Microbiology and Infection
Amara Gul, Sadia Zafar
The objective of the current study was to compare cognitive flexibility and emotion regulation between childhood survivors of Acute Lymphoblastic Leukaemia (ALL) and healthy control subjects. Twenty-five childhood survivors of ALL treated with intrathecal chemotherapy between 2013 to 2016 from Shaukat Khanum Memorial Cancer Hospital, Children Hospital and Jinnah Hospital Lahore and twenty-five healthy demographically matched children (control group) participated in the study. Participants performed task switching experiment as a measure of cognitive flexibility and emotion regulation questionnaire for children and adolescents...
March 2018: JPMA. the Journal of the Pakistan Medical Association
Lisa M Ebert, Wenbo Yu, Tessa Gargett, Michael P Brown
Chimeric antigen receptor (CAR)-T cell therapy has been clinically validated as a curative treatment for the difficult to treat malignancies of relapsed/refractory B-cell acute lymphoblastic leukaemia and lymphoma. Here, the CAR-T cells are re-directed towards a single antigen, CD19, which is recognised as a virtually ideal CAR target antigen because it has strong, uniform expression on cancer cells, and is otherwise expressed only on healthy B cells, which are 'dispensable'. Notwithstanding the clinical success of CD19-CAR-T cell therapy, its single specificity has driven therapeutic resistance in 30% or more of cases with CD19-negative leukaemic relapses...
March 14, 2018: Biochemical Society Transactions
Inna M Yasinska, Giacomo Ceccone, Isaac Ojea-Jimenez, Jessica Ponti, Rohanah Hussain, Giuliano Siligardi, Steffen M Berger, Elizaveta Fasler-Kan, Marco Bardelli, Luca Varani, Walter Fiedler, Jasmin Wellbrock, Ulrike Raap, Bernhard F Gibbs, Luigi Calzolai, Vadim V Sumbayev
In this study we used 5 nm gold nanoparticles as delivery platforms to target cancer cells expressing the immune receptor Tim-3 using single chain antibodies. Gold surfaces were also covered with the cytotoxic drug rapamycin which was immobilised using a glutathione linker. These nanoconjugates allowed highly specific and efficient delivery of cytotoxic rapamycin into human malignant blood cells.
March 14, 2018: Nanoscale
Federica Vezzali, Silvia Grassilli, Elisabetta Lambertini, Federica Brugnoli, Simone Patergnani, Ervin Nika, Roberta Piva, Paolo Pinton, Silvano Capitani, Valeria Bertagnolo
It has been recently demonstrated that high pre-treatment levels of miR-29b positively correlated with the response of patients with acute myeloid leukaemia (AML) to hypomethylating agents. Upmodulation of miR-29b by restoring its transcriptional machinery appears indeed a tool to improve therapeutic response in AML. In cells from acute promyelocytic leukaemia (APL), miR-29b is regulated by PU.1, in turn upmodulated by agonists currently used to treat APL. We explored here the ability of PU.1 to also regulate miR-29b in non-APL cells, in order to identify agonists that, upmodulating PU...
March 13, 2018: Journal of Cellular and Molecular Medicine
Barbara J McClure, Susan L Heatley, Chung H Kok, Teresa Sadras, Jiyuan An, Timothy P Hughes, Richard B Lock, David Yeung, Rosemary Sutton, Deborah L White
BACKGROUND: Zinc-finger protein 384 (ZNF384) fusions are an emerging subtype of precursor B-cell acute lymphoblastic leukaemia (pre-B-ALL) and here we further characterised their prevalence, survival outcomes and transcriptome. METHODS: Bone marrow mononuclear cells from 274 BCR-ABL1-negative pre-B-ALL patients were immunophenotyped and transcriptome molecularly characterised. Transcriptomic data was analysed by principal component analysis and gene-set enrichment analysis to identify gene and pathway expression changes...
March 13, 2018: British Journal of Cancer
Xiu Fen Chen, Joe Yeong, Kenneth Tou En Chang, Alvin Soon Tiong Lim, Chik Hong Kuick, Tse Hui Lim, Jain Sudhanshi, Sathiyamoorthy Selvarajan, Valerie Huei Li Gan, Li Yan Khor
Perivascular epithelioid cell tumor (PEComa) is an uncommon tumor which presents with epithelioid and spindled cell morphology and is immunoreactive for myogenic and melanocytic markers. Recently, a subset of PEComas has been reported to harbor TFE3 gene rearrangement.In this case report, we describe a TFE3 -expressing primary bladder PEComa in a 27-year-old male patient with acute myeloid leukaemia in remission. The tumor displayed epithelioid morphology with surrounding delicate blood vessels and was devoid of a prominent spindle cell component...
January 2018: Annals of Clinical and Laboratory Science
Andreas K Øvlisen, Anders Oest, Mette D Bendtsen, John Bæch, Preben Johansen, Line S Lynggaard, Ingolf Mølle, Thomas B Mortensen, Duruta Weber, Gideon Ertner, Claudia Schöllkopf, Jesper Q Thomassen, Ove Juul Nielsen, Lene Sofie Granfeldt Østgård, Martin Bøgsted, Karen Dybkær, Hans E Johnsen, Marianne T Severinsen
Stringent complete remission (sCR) of acute myeloid leukemia is defined as normal hematopoiesis after therapy. Less sCR, including non-sCR, was introduced as insufficient blood platelet, neutrophil, or erythrocyte recovery. These latter characteristics were defined retrospectively as postremission transfusion dependency and were suggested to be of prognostic value. In the present report, we evaluated the prognostic impact of achieving sCR and non-sCR in the Danish National Acute Leukaemia Registry, including 769 patients registered with classical CR (ie, <5% blasts in the postinduction bone marrow analysis)...
March 13, 2018: Blood Advances
Xiang-Lei Chen, Yuan-Hua Cai, Qiao Liu, Li-Li Pan, Shui-Ling Shi, Xiao-Li Liu, Yuan Chen, Jing-Gang Li, Jing Wang, Yang Li, Xiao-Fan Li, Shao-Yuan Wang
DHX15 plays a role in leukaemogenesis and leukaemia relapse. However, the mechanism underlying the transcriptional regulation of DHX15 in ALL has not been elucidated. Our present study aimed to explore the functional promoter region of DHX15 and to investigate the transcription factors controlling the transcription of this gene. A luciferase assay performed with several truncated constructs identified a 501-bp region as the core promoter region of DHX15. Site-directed mutagenesis, electrophoretic mobility shift and chromatin immunoprecipitation assays showed that ETS1 and SP1 occupied the DHX15 promoter...
March 7, 2018: Journal of Cellular and Molecular Medicine
Joanna Drozd-Sokołowska, Krzysztof Mądry, Anna Waszczuk-Gajda, Przemysław Biecek, Paweł Szwedyk, Katarzyna Budziszewska, Magdalena Raźny, Magdalena Dutka, Agata Obara, Ewa Wasilewska, Krzysztof Lewandowski, Agnieszka Piekarska, Grażyna Bober, Helena Krzemień, Beata Stella-Hołowiecka, Katarzyna Kapelko-Słowik, Waldemar Sawicki, Małgorzata Paszkowska-Kowalewska, Rafał Machowicz, Jadwiga Dwilewicz-Trojaczek
Atypical chronic myeloid leukaemia (aCML) belongs to myelodysplastic/myeloproliferative neoplasms. Because of its rarity and changing diagnostic criteria throughout subsequent classifications, data on aCML are very scarce. Therefore, we at the Polish Adult Leukemia Group performed a nationwide survey on aCML. Eleven biggest Polish centres participated in the study. Altogether, 45 patients were reported, among whom only 18 patients (40%) fulfilled diagnostic criteria. Among misdiagnosed patients, myelodysplastic/myeloproliferative syndrome unclassifiable and chronic myelomonocytic leukaemia were the most frequent diagnoses...
March 7, 2018: Hematological Oncology
Inês Mourato Nunes, Ana Isabel Pedroso, Ramiro Carvalho, Armindo Ramos
Pathological or spontaneous splenic rupture is a rare but well-recognised complication of haematological malignancies. The authors present a clinical report of a 78-year-old woman with known clinical history of chronic lymphocytic leukaemia and atrial fibrillation under anticoagulation with apixaban which has spontaneous splenic rupture. Pathological examination revealed lymph node and splenic infiltration due to chronic lymphocytic leukaemia. The diagnosis of splenic rupture must be considered in all patients with haematological malignancies who experience acute abdomen...
March 5, 2018: BMJ Case Reports
Ping Leng, Zhao Yang, Baohua Ma, Jing Li, Jialin Sun, Yiming Xie, Yong Sun
A compound (WJD-A-1) was previously reported as a candidate prodrug of Am80 (tamibarotene), which was approved in Japan in 2005 as a therapeutic agent for recurrent refractory acute promyelocytic leukaemia. A rapid, selective and sensitive ultra high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed for the first time to simultaneously determine WJD-A-1 and its major phase-I metabolites AM80 in rat plasma. After a simple sample preparation procedure by protein precipitation with methanol and acetonitrile, WJD-A-1, AM80 and the internal standard were chromatographed on an ACQUITY UPLCTM BEH C18 column...
March 5, 2018: Artificial Cells, Nanomedicine, and Biotechnology
Lene S G Østgård, Mette Nørgaard, Lars Pedersen, René D Østgård, Bruno C Medeiros, Ulrik M Overgaard, Claudia Schöllkopf, Marianne Severinsen, Claus W Marcher, Morten K Jensen
Previous studies reported increased risk of acute myeloid leukaemia (AML) in individuals with inflammatory conditions. However, it is unclear whether this association is explained by preceding cytotoxic therapy or haematological diseases. We conducted a nationwide case-control study that included 3053 AML patients, diagnosed in Denmark between 2000 and 2013, and 30 530 sex- and age-matched population controls. We retrieved information on autoimmune disease, infections, and use of antibiotics and computed odds ratios for AML (conditional logistic regression)...
March 5, 2018: British Journal of Haematology
Matt Stevenson, Abdullah Pandor, Jean Hamilton, John Stevens, Clare Rowntree, Marrissa Martyn-St James, Andrew Rawdin, Ruth Wong
As part of its single technology appraisal (STA) process, the UK National Institute for Health and Care Excellence (NICE) invited the manufacturer (Incyte Corporation) of ponatinib (Inclusig® ) to submit evidence of its clinical and cost effectiveness for previously treated Philadelphia-chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL) and chronic myeloid leukaemia. This paper focusses on Ph+ ALL. The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent evidence review group (ERG)...
March 3, 2018: PharmacoEconomics
S-M Wang, W-X Zeng, W-S Wu, L-L Sun, D Yan
WHAT IS KNOWN AND OBJECTIVE: Thymidylate synthase (TYMS) is an important target for methotrexate (MTX). Genetic variations in the TYMS gene contribute to the differences in treatment responses to MTX. The aim of this study was to investigate the distribution of a microRNA (miRNA) binding site polymorphism (rs2790 A > G) in the 3'-untranslated region (3'-UTR) of TYMS and its association with MTX concentration and haematological toxicity in Chinese paediatric patients with acute lymphoblastic leukaemia (ALL)...
March 3, 2018: Journal of Clinical Pharmacy and Therapeutics
Giovanni D'Arena, Giuseppe Pietrantuono, Pellegrino Musto
No abstract text is available yet for this article.
March 2, 2018: Postgraduate Medical Journal
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