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Acute lymphoblastic leukaemia

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https://www.readbyqxmd.com/read/28299660/etv6-runx1-acute-lymphoblastic-leukaemia-in-identical-twins
#1
Anthony M Ford, Mel Greaves
Acute leukaemia is the major subtype of paediatric cancer with a cumulative risk of 1 in 2000 for children up to the age of 15 years. Childhood acute lymphoblastic leukaemia (ALL) is a biologically and clinically diverse disease with distinctive subtypes; multiple chromosomal translocations exist within the subtypes and each carries its own prognostic relevance. The most common chromosome translocation observed is the t(12;21) that results in an in-frame fusion between the first five exons of ETV6 (TEL) and almost the entire coding region of RUNX1 (AML1)...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28295194/anti-leukaemic-activity-of-the-tyk2-selective-inhibitor-ndi-031301-in-t-cell-acute-lymphoblastic-leukaemia
#2
Koshi Akahane, Zhaodong Li, Julia Etchin, Alla Berezovskaya, Evisa Gjini, Craig E Masse, Wenyan Miao, Jennifer Rocnik, Rosana Kapeller, Jeremy R Greenwood, Hong Tiv, Takaomi Sanda, David M Weinstock, A Thomas Look
Activation of tyrosine kinase 2 (TYK2) contributes to the aberrant survival of T-cell acute lymphoblastic leukaemia (T-ALL) cells. Here we demonstrate the anti-leukaemic activity of a novel TYK2 inhibitor, NDI-031301. NDI-031301 is a potent and selective inhibitor of TYK2 that induced robust growth inhibition of human T-ALL cell lines. NDI-031301 treatment of human T-ALL cell lines resulted in induction of apoptosis that was not observed with the JAK inhibitors tofacitinib and baricitinib. Further investigation revealed that NDI-031301 treatment uniquely leads to activation of three mitogen-activated protein kinases (MAPKs), resulting in phosphorylation of ERK, SAPK/JNK and p38 MAPK coincident with PARP cleavage...
March 14, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28295182/a-phase-1-trial-of-temsirolimus-and-intensive-re-induction-chemotherapy-for-2nd-or-greater-relapse-of-acute-lymphoblastic-leukaemia-a-children-s-oncology-group-study-advl1114
#3
Susan R Rheingold, Sarah J Tasian, James A Whitlock, David T Teachey, Michael J Borowitz, Xiaowei Liu, Charles G Minard, Elizabeth Fox, Brenda J Weigel, Susan M Blaney
The phosphatidylinositol 3-kinase (PI3K)/mammalian (or mechanistic) target of rapamycin (mTOR) signalling pathway is commonly dysregulated in acute lymphoblastic leukaemia (ALL). A phase 1 trial of the mTOR inhibitor temsirolimus in combination with UKALL R3 re-induction chemotherapy was conducted in children and adolescents with second or greater relapse of ALL. The initial temsirolimus dose level (DL1) was 10 mg/m(2) weekly × 3 doses. Subsequent patient cohorts received temsirolimus 7·5 mg/m(2) weekly × 3 doses (DL0) or, secondary to toxicity, 7·5 mg/m(2) weekly × 2 doses (DL-1)...
March 14, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28283471/unilateral-facial-nerve-palsy-as-an-early-presenting-symptom-of-relapse-in-a-paediatric-patient-with-acute-lymphoblastic-leukaemia
#4
Leslie Y Chiang, John Ross Crawford, Dennis John Kuo
No abstract text is available yet for this article.
March 10, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28260788/apobec-signature-mutation-generates-an-oncogenic-enhancer-that-drives-lmo1-expression-in-t-all
#5
Z Li, B J Abraham, A Berezovskaya, N Farah, Y Liu, T Leon, A Fielding, S H Tan, T Sanda, A S Weintraub, B Li, S Shen, J Zhang, M R Mansour, R A Young, A T Look
Oncogenic driver mutations are those that provide a proliferative or survival advantage to neoplastic cells resulting in clonal selection. Although most cancer causing mutations have been detected in the protein-coding regions of the cancer genome, driver mutations have recently also been discovered within noncoding genomic sequences. Thus, a current challenge is to gain precise understanding of how these unique genomic elements function in cancer pathogenesis, while clarifying mechanisms of gene regulation and identifying new targets for therapeutic intervention...
March 6, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28258829/mercaptopurine-in-childhood-acute-lymphoblastic-leukaemia
#6
Paul S Gaynon
No abstract text is available yet for this article.
February 28, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28258828/dna-thioguanine-nucleotide-concentration-and-relapse-free-survival-during-maintenance-therapy-of-childhood-acute-lymphoblastic-leukaemia-nopho-all2008-a-prospective-substudy-of-a-phase-3-trial
#7
Stine Nygaard Nielsen, Kathrine Grell, Jacob Nersting, Jonas Abrahamsson, Bendik Lund, Jukka Kanerva, Ólafur Gísli Jónsson, Goda Vaitkeviciene, Kaie Pruunsild, Lisa Lyngsie Hjalgrim, Kjeld Schmiegelow
BACKGROUND: Adjustment of mercaptopurine and methotrexate maintenance therapy of acute lymphoblastic leukaemia by leucocyte count is confounded by natural variations. Cytotoxicity is primarily mediated by DNA-incorporated thioguanine nucleotides (DNA-TGN). The aim of this study was to establish whether DNA-TGN concentrations in blood leucocytes during maintenance therapy are associated with relapse-free survival. METHODS: In this substudy of the NOPHO ALL2008 phase 3 trial done in 23 hospitals in seven European countries (Denmark, Estonia, Finland, Iceland, Lithuania, Norway, and Sweden), we analysed data from centralised and blinded analyses of 6-mercaptopurine and methotrexate metabolites in blood samples from patients with non-high-risk childhood acute lymphoblastic leukaemia...
February 28, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28256501/genetic-and-regulatory-mechanism-of-susceptibility-to-high-hyperdiploid-acute-lymphoblastic-leukaemia-at-10p21-2
#8
James B Studd, Jayaram Vijayakrishnan, Minjun Yang, Gabriele Migliorini, Kajsa Paulsson, Richard S Houlston
Despite high-hyperdiploid acute lymphoblastic leukaemia (HD-ALL) being the most common subgroup of paediatric ALL, its aetiology remains unknown. Genome-wide association studies have demonstrated association at 10q21.2. Here, we sought to determine how this region influences HD-ALL risk. We impute genotypes across the locus, finding the single nucleotide polymorphism rs7090445 highly associated with HD-ALL (P=1.54 × 10(-38)), and residing in a predicted enhancer element. We show this region physically interacts with the transcription start site of ARID5B, that alleles of rs7090445 have differential enhancer activity and influence RUNX3 binding...
March 3, 2017: Nature Communications
https://www.readbyqxmd.com/read/28244858/the-assessment-and-appraisal-of-regenerative-medicines-and-cell-therapy-products-an-exploration-of-methods-for-review-economic-evaluation-and-appraisal
#9
Robert Hettle, Mark Corbett, Sebastian Hinde, Robert Hodgson, Julie Jones-Diette, Nerys Woolacott, Stephen Palmer
BACKGROUND: The National Institute for Health and Care Excellence (NICE) commissioned a 'mock technology appraisal' to assess whether changes to its methods and processes are needed. This report presents the findings of independent research commissioned to inform this appraisal and the deliberations of a panel convened by NICE to evaluate the mock appraisal. METHODS: Our research included reviews to identify issues, analysis methods and conceptual differences and the relevance of alternative decision frameworks, alongside the development of an exemplar case study of chimeric antigen receptor (CAR) T-cell therapy for treating acute lymphoblastic leukaemia...
February 2017: Health Technology Assessment: HTA
https://www.readbyqxmd.com/read/28225754/targeting-a-car-to-the-trac-locus-with-crispr-cas9-enhances-tumour-rejection
#10
Justin Eyquem, Jorge Mansilla-Soto, Theodoros Giavridis, Sjoukje J C van der Stegen, Mohamad Hamieh, Kristen M Cunanan, Ashlesha Odak, Mithat Gönen, Michel Sadelain
Chimeric antigen receptors (CARs) are synthetic receptors that redirect and reprogram T cells to mediate tumour rejection. The most successful CARs used to date are those targeting CD19 (ref. 2), which offer the prospect of complete remission in patients with chemorefractory or relapsed B-cell malignancies. CARs are typically transduced into the T cells of a patient using γ-retroviral vectors or other randomly integrating vectors, which may result in clonal expansion, oncogenic transformation, variegated transgene expression and transcriptional silencing...
February 22, 2017: Nature
https://www.readbyqxmd.com/read/28224842/-the-transition-to-palliative-care-is-profoundly-emotional
#11
Jennifer Trueland
In the past 20 years or so, the outlook for children diagnosed with cancer has changed dramatically. New treatments have transformed outcomes and the prognosis is generally positive, particularly for the most common childhood cancer, acute lymphoblastic leukaemia. But that is not true for everyone; some children with cancer will die.
February 22, 2017: Nursing Standard
https://www.readbyqxmd.com/read/28218349/mri-and-18f-fdg-pet-ct-in-a-rare-case-of-early-precursor-b-lymphoblastic-leukaemia-with-bone-involvement-as-initial-manifestation
#12
Angelina Cistaro, Vincenzo La Delfa, Gianpaolo Di Rosa, Maurizio Cogoni, Natale Quartuccio
A 4-year old girl presenting gait difficulty was referred for spine X-ray and Magnetic Resonance Imaging (MRI). MRI showed several diffuse hypointense signals in sacral and lumbar vertebrae. In order to exclude a possible lymphoproliferative disease a 18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) was requested. The PET/CT scan confirmed the MRI findings and demonstrated additional findings in the sternum. Therefore, a bone marrow biopsy was performed and a diagnosis of acute lymphoblastic leukaemia - early B type was made...
2017: Nuclear Medicine Review. Central & Eastern Europe
https://www.readbyqxmd.com/read/28215040/who-should-receive-a-transplant-for-acute-lymphoblastic-leukaemia
#13
REVIEW
Rishi Dhawan, David I Marks
Allogeneic haematopoietic cell transplantation continues to be an important curative therapy for acute lymphoblastic leukaemia (ALL). Traditionally accepted indications for allografting adult ALL patients need reevaluation in light of outcomes with paediatric-like intensive regimens. Minimal residual disease status and oncogenetics can be used for restratification of standard risk patients. A greater body of data on haematopoietic cell transplantation (HCT) outcomes from haploidentical and cord blood donor sources has been generated in recent years...
February 18, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28211568/targeted-therapies-for-t-cell-acute-lymphoblastic-leukaemia-t-all-what-makes-t-all-tyk
#14
EDITORIAL
David J Curtis
No abstract text is available yet for this article.
February 17, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28208868/female-genital-tract-involvement-in-acute-lymphoblastic-leukemia-a-rare-case-report
#15
Vikram Narang, Amit Dhiman, Bhavna Garg, Neena Sood
Female Genital Tract (FGT) involvement with hematologic neoplasms is uncommon and the hematologic malignancies which involve the female genital organs are usually non-Hodgkin's lymphoma. Involvement of the uterus and cervix with Acute Lymphoblastic Leukaemia (ALL) is extremely rare, and ovarian involvement is even rarer. We report the case of a young lady who presented with tubo-ovarian mass, excessive post-operative bleeding (post-total abdominal hystrerctomy and bilateral salpingo-oophorectomy) and was diagnosed to have ALL with blood and tissue involvement by histopathology and flow cytometry...
December 2016: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28192788/metabolic-gatekeeper-function-of-b-lymphoid-transcription-factors
#16
Lai N Chan, Zhengshan Chen, Daniel Braas, Jae-Woong Lee, Gang Xiao, Huimin Geng, Kadriye Nehir Cosgun, Christian Hurtz, Seyedmehdi Shojaee, Valeria Cazzaniga, Hilde Schjerven, Thomas Ernst, Andreas Hochhaus, Steven M Kornblau, Marina Konopleva, Miles A Pufall, Giovanni Cazzaniga, Grace J Liu, Thomas A Milne, H Phillip Koeffler, Theodora S Ross, Isidro Sánchez-García, Arndt Borkhardt, Keith R Yamamoto, Ross A Dickins, Thomas G Graeber, Markus Müschen
B-lymphoid transcription factors, such as PAX5 and IKZF1, are critical for early B-cell development, yet lesions of the genes encoding these transcription factors occur in over 80% of cases of pre-B-cell acute lymphoblastic leukaemia (ALL). The importance of these lesions in ALL has, until now, remained unclear. Here, by combining studies using chromatin immunoprecipitation with sequencing and RNA sequencing, we identify a novel B-lymphoid program for transcriptional repression of glucose and energy supply...
February 13, 2017: Nature
https://www.readbyqxmd.com/read/28187480/-acute-lymphoblastic-leukaemia-in-adults
#17
Nicola Gökbuget
No abstract text is available yet for this article.
February 2017: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/28182813/second-malignant-neoplasms-in-childhood-cancer-survivors-treated-in-a-tertiary-paediatric-oncology-centre
#18
Jia Wei Lim, Frances Sh Yeap, Yiong Huak Chan, Allen Ej Yeoh, Thuan Chong Quah, Poh Lin Tan
Introduction: One of the most feared complications of childhood cancer treatment is second malignant neoplasms (SMNs). This study evaluates the incidence, risk factors and outcomes of SMNs in a tertiary paediatric oncology centre in Singapore. Materials and Methods: A retrospective review was conducted on patients diagnosed with childhood cancer under age 21 and treated at the National University Hospital, Singapore, from January 1990 to 15 April 2012. Case records of patients with SMNs were reviewed. Results: We identified 1124 cases of childhood cancers with a median follow-up of 3...
January 2017: Annals of the Academy of Medicine, Singapore
https://www.readbyqxmd.com/read/28179388/disseminated-intravascular-coagulation-like-reaction-following-rituximab-infusion
#19
Hind Rafei, Samah Nassereddine, Ivan F Garcia
Rituximab generally is a well-tolerated medication used in a variety of haematological and autoimmune conditions. The safety profile of the medication has been reviewed in the literature. Infusion reactions due to cytokine release are the most common side effects. With the increased use of rituximab, there is an increase incidence of cytopenias, most commonly thrombocytopenia and leucopenia. Coagulopathy is quite rare, reported previously in four cases in the literature. We highlighted the clinical course of a 39-year-old patient with precursor B-cell acute lymphoblastic leukaemia who was started on rituximab infusion...
February 8, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28139933/functionalized-triblock-copolymer-vectors-for-the-treatment-of-acute-lymphoblastic-leukemia
#20
Robert C Deller, Paraskevi Diamanti, Gabriella Morrison, James Reilly, Benjamin C Ede, Robert Richardson, Kristian Le Vay, Andrew M Collins, Allison Blair, Adam W Perriman
The chemotherapeutic Parthenolide is an exciting new candidate for the treatment of acute lymphoblastic leukemia, but like many other small-molecule drugs, it has low aqueous solubility. As a consequence, Parthenolide can only be administered clinically in the presence of harmful cosolvents. Accordingly, we describe the synthesis, characterization, and testing of a range of biocompatible triblock copolymer micelles as particle-based delivery vectors for the hydrophobic drug Parthenolide. The drug-loaded particles are produced via an emulsion-to-micelle transition method, and the effects of introducing anionic and cationic surface charges on stability, drug sequestration, biocompatibility, and efficacy are investigated...
February 16, 2017: Molecular Pharmaceutics
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