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Acute lymphoblastic leukaemia

Aditya Jandial, Kundan Mishra, Alka Khadwal, Pankaj Malhotra
No abstract text is available yet for this article.
March 20, 2018: BMJ Case Reports
Caroline L Furness, Marcela B Mansur, Victoria J Weston, Luca Ermini, Frederik W van Delft, Sarah Jenkinson, Rosemary Gale, Christine J Harrison, Maria S Pombo-de-Oliveira, Marta Sanchez-Martin, Adolfo A Ferrando, Pamela Kearns, Ian Titley, Anthony M Ford, Nicola E Potter, Mel Greaves
Single-cell genetics were used to interrogate clonal complexity and the sequence of mutational events in STIL-TAL1+ T-ALL. Single-cell multicolour FISH was used to demonstrate that the earliest detectable leukaemia subclone contained the STIL-TAL1 fusion and copy number loss of 9p21.3 (CDKN2A/CDKN2B locus), with other copy number alterations including loss of PTEN occurring as secondary subclonal events. In three cases, multiplex qPCR and phylogenetic analysis were used to produce branching evolutionary trees recapitulating the snapshot history of T-ALL evolution in this leukaemia subtype, which confirmed that mutations in key T-ALL drivers, including NOTCH1 and PTEN, were subclonal and reiterative in distinct subclones...
March 20, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Maro Ohanian, Ana Tari Ashizawa, Guillermo Garcia-Manero, Naveen Pemmaraju, Tapan Kadia, Elias Jabbour, Farhad Ravandi, Gautam Borthakur, Michael Andreeff, Marina Konopleva, Miranda Lim, Sherry Pierce, Susan O'Brien, Yesid Alvarado, Srdan Verstovsek, William Wierda, Hagop Kantarjian, Jorge Cortes
BACKGROUND: Activating mutations of tyrosine kinases are common in leukaemias. Oncogenic tyrosine kinases use the growth factor receptor-bound protein 2 (Grb2) for signal transduction, leading to activation of mitogen-activated protein kinase (MAPK) 1 and MAPK3 (ERK2 and ERK1). We hypothesised that inhibition of Grb2 would suppress ERK1 and ERK2 activation and inhibit leukaemia progression. To inhibit Grb2, a liposome-incorporated antisense oligodeoxynucleotide that blocks Grb2 protein expression, BP1001, was developed...
March 14, 2018: Lancet Haematology
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
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
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
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
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
Josefina Reyes-Sebastian, Laura Arcelia Montiel-Cervantes, Elba Reyes-Maldonado, Maria Lilia Dominguez-Lopez, Rocio Ortiz-Butron, Aida Castillo-Alvarez, Ruth Angélica Lezama
Receptor tyrosine kinase (RTK) activity may contribute to carcinogenesis. The c-Kit receptor, a member of the RTK family, is expressed in immature haematopoietic system cells. Acute lymphoblastic leukaemia (ALL) presents incompletely differentiated lymphoblasts, and consequently, c-Kit expression can be detected in these cells. The BCR-ABL kinase, which is usually present in both ALL and chronic myeloid leukaemia, can trigger signalling pathways with neoplastic effects. However, a certain number of ALL patients and chronic myeloid leukaemia patients do not express this kinase, raising the question of which other proteins that intervene in signalling pathways may be involved in the development of these diseases...
March 1, 2018: Hematology (Amsterdam, Netherlands)
E C Akinsal, N Baydilli, M E Dogan, O Ekmekcioglu
Congenital absence of the vas deferens (CAVD) is a relatively rare anomaly that may contribute to male infertility. The aim of this study was to evaluate the clinical features of patients with CAVD and to emphasise some pathological conditions that may be detected during the infertility work-up or follow-up of these patients. The charts of 150 males with the diagnosis of CAVD were evaluated retrospectively. The demographic characteristics, reasons for attendance, the way of diagnosis, interventions for infertility before and after attendance, physical examination findings, reproductive hormone levels, semen analysis results, genetical analysis results and resultant live birth events were all included in the study...
February 27, 2018: Andrologia
Abdullah Pandor, Matt Stevenson, John Stevens, Marrissa Martyn-St James, Jean Hamilton, Jenny Byrne, Claudius Rudin, Andrew Rawdin, Ruth Wong
As part of its single technology appraisal process, the National Institute for Health and Care Excellence (NICE) invited the company that manufactures ponatinib (Inclusig® ; Incyte Corporation) to submit evidence for the clinical and cost effectiveness for previously treated chronic myeloid leukaemia (CML) and Philadelphia-chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL). This paper focusses on the three phases of CML: the chronic phase (CP), the accelerated phase (AP) and the blast crisis phase (BP)...
February 26, 2018: PharmacoEconomics
Nan B Oldereid, Ulla-Britt Wennerholm, Anja Pinborg, Anne Loft, Hannele Laivuori, Max Petzold, Liv Bente Romundstad, Viveca Söderström-Anttila, Christina Bergh
BACKGROUND: Maternal factors, including increasing childbearing age and various life-style factors, are associated with poorer short- and long-term outcomes for children, whereas knowledge of paternal parameters is limited. Recently, increasing paternal age has been associated with adverse obstetric outcomes, birth defects, autism spectrum disorders and schizophrenia in children. OBJECTIVE AND RATIONALE: The aim of this systematic review is to describe the influence of paternal factors on adverse short- and long-term child outcomes...
February 15, 2018: Human Reproduction Update
Abdullah Faisal Aldairi, Olanrewaju Dorcas Ogundipe, David Alexander Pye
Despite the increasing availability of new classes of cancer treatment, such as immune- and targeted therapies, there remains a need for the development of new antiproliferative/cytotoxic drugs with improved pharmacological profiles that can also overcome drug resistant forms of cancer. In this study, we have identified, and characterised, a novel marine polysaccharide with the potential to be developed as an anticancer agent. Sulphated polysaccharides isolated from the common cockle ( Cerastoderma edule ) were shown to have antiproliferative activity on chronic myelogenous leukaemia and relapsed acute lymphoblastic leukaemia cell lines...
February 15, 2018: Marine Drugs
Chien-Yuan Chen, Wang-Huei Sheng, Feng-Ming Tien, Po-Chu Lee, Shang-Yi Huang, Jih-Luh Tang, Woei Tsay, Hwei-Fang Tien, Po-Ren Hsueh
BACKGROUND/PURPOSE: This study was aimed to investigate clinical characteristics and treatment outcomes of pulmonary invasive fungal infection (IFI) among patients with hematological malignancy. METHODS: All patients with hematological malignancy who were treated at a medical centre from 2008 to 2013 were evaluated. Pulmonary IFI was classified according to the European Organization for Research and Treatment of Cancer 2008 consensus. RESULTS: During the study period, 236 (11...
January 31, 2018: Journal of Microbiology, Immunology, and Infection, Wei Mian Yu Gan Ran za Zhi
Alejandro Gutierrez, Alex Kentsis
Advances in the classification of acute leukaemias have led to improved outcomes for a substantial fraction of patients. However, chemotherapy resistance remains a major problem for specific subsets of acute leukaemias. Here, we propose that a molecularly distinct subtype of acute leukaemia with shared myeloid and T cell lymphoblastic features, which we term acute myeloid/T-lymphoblastic leukaemia (AMTL), is divided across 3 diagnostic categories owing to variable expression of markers deemed to be defining of myeloid and T-lymphoid lineages, such as myeloperoxidase and CD3...
February 14, 2018: British Journal of Haematology
Volker Strenger, Gerald Merth, Herwig Lackner, Stephan W Aberle, Harald H Kessler, Markus G Seidel, Wolfgang Schwinger, Daniela Sperl, Petra Sovinz, Anna Karastaneva, Martin Benesch, Christian Urban
Haemophagocytic lymphohistiocytosis (HLH) is a possibly life-threatening syndrome of immune dysregulation and can be divided into primary (hereditary) and secondary forms (including malignancy-associated HLH (M-HLH)). We retrospectively analysed epidemiological, clinical, virological and laboratory data from patients with M-HLH treated at our department between 1995 and 2014. Out of 1.706 haemato-/oncologic patients treated at our department between 1995 and 2014, we identified 22 (1.29%) patients with secondary HLH (1...
February 6, 2018: Annals of Hematology
Claudia Allemani, Tomohiro Matsuda, Veronica Di Carlo, Rhea Harewood, Melissa Matz, Maja Nikšić, Audrey Bonaventure, Mikhail Valkov, Christopher J Johnson, Jacques Estève, Olufemi J Ogunbiyi, Gulnar Azevedo E Silva, Wan-Qing Chen, Sultan Eser, Gerda Engholm, Charles A Stiller, Alain Monnereau, Ryan R Woods, Otto Visser, Gek Hsiang Lim, Joanne Aitken, Hannah K Weir, Michel P Coleman
BACKGROUND: In 2015, the second cycle of the CONCORD programme established global surveillance of cancer survival as a metric of the effectiveness of health systems and to inform global policy on cancer control. CONCORD-3 updates the worldwide surveillance of cancer survival to 2014. METHODS: CONCORD-3 includes individual records for 37·5 million patients diagnosed with cancer during the 15-year period 2000-14. Data were provided by 322 population-based cancer registries in 71 countries and territories, 47 of which provided data with 100% population coverage...
January 30, 2018: Lancet
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