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acute leukaemia

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https://www.readbyqxmd.com/read/29164635/influence-of-genetic-variants-of-idh1-idh2-tet2-and-dnmt3a-on-cytarabine-cytotoxicity-in-different-populations
#1
Y Wang, J K Lamba
WHAT IS KNOWN AND OBJECTIVE: Cytarabine (ara-C) is the mainstay of treatment for acute myeloid leukaemia. Resistance and toxicity are common reasons for its treatment failure. Genetic variants of susceptibility genes may be involved in resistance and toxicity to ara-C. This study is aimed to explore the association between influence of genetic variants of IDH1, IDH2, TET2 and DNMT3A on cytarabine cytotoxicity in European and/or African populations. METHODS: HapMap cell lines derived from European descent (CEU) and African descent (YRI) were exposed to ara-C at different concentrations (1, 5, 40 and 80 μmol/L)...
November 21, 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/29153976/image-based-ex-vivo-drug-screening-for-patients-with-aggressive-haematological-malignancies-interim-results-from-a-single-arm-open-label-pilot-study
#2
Berend Snijder, Gregory I Vladimer, Nikolaus Krall, Katsuhiro Miura, Ann-Sofie Schmolke, Christoph Kornauth, Oscar Lopez de la Fuente, Hye-Soo Choi, Emiel van der Kouwe, Sinan Gültekin, Lukas Kazianka, Johannes W Bigenzahn, Gregor Hoermann, Nicole Prutsch, Olaf Merkel, Anna Ringler, Monika Sabler, Georg Jeryczynski, Marius E Mayerhoefer, Ingrid Simonitsch-Klupp, Katharina Ocko, Franz Felberbauer, Leonhard Müllauer, Gerald W Prager, Belgin Korkmaz, Lukas Kenner, Wolfgang R Sperr, Robert Kralovics, Heinz Gisslinger, Peter Valent, Stefan Kubicek, Ulrich Jäger, Philipp B Staber, Giulio Superti-Furga
BACKGROUND: Patients with refractory or relapsed haematological malignancies have few treatment options and short survival times. Identification of effective therapies with genomic-based precision medicine is hampered by intratumour heterogeneity and incomplete understanding of the contribution of various mutations within specific cancer phenotypes. Ex-vivo drug-response profiling in patient biopsies might aid effective treatment identification; however, proof of its clinical utility is limited...
November 15, 2017: Lancet Haematology
https://www.readbyqxmd.com/read/29152058/effective-control-of-acute-myeloid-leukaemia-and-acute-lymphoblastic-leukaemia-progression-by-telomerase-specific-adoptive-t-cell-therapy
#3
Sara Sandri, Francesco De Sanctis, Alessia Lamolinara, Federico Boschi, Ornella Poffe, Rosalinda Trovato, Alessandra Fiore, Sara Sartori, Andrea Sbarbati, Attilio Bondanza, Simone Cesaro, Mauro Krampera, Maria T Scupoli, Michael I Nishimura, Manuela Iezzi, Silvia Sartoris, Vincenzo Bronte, Stefano Ugel
Telomerase (TERT) is a ribonucleoprotein enzyme that preserves the molecular organization at the ends of eukaryotic chromosomes. Since TERT deregulation is a common step in leukaemia, treatments targeting telomerase might be useful for the therapy of hematologic malignancies. Despite a large spectrum of potential drugs, their bench-to-bedside translation is quite limited, with only a therapeutic vaccine in the clinic and a telomerase inhibitor at late stage of preclinical validation. We recently demonstrated that the adoptive transfer of T cell transduced with an HLA-A2-restricted T-cell receptor (TCR), which recognize human TERT with high avidity, controls human B-cell chronic lymphocytic leukaemia (B-CLL) progression without severe side-effects in humanized mice...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29149345/predictive-indicators-to-identify-high-risk-paediatric-febrile-neutropenia-in-paediatric-oncology-patients-in-a-middle-income-country
#4
Lindy-Lee Green, Pierre Goussard, Anel van Zyl, Martin Kidd, Mariana Kruger
Purpose: To validate a clinical risk prediction score (Ammann score) to predict adverse events (AEs) in paediatric febrile neutropenia (FN). Patients and methods: Patients <16 years of age were enrolled. A risk prediction score (based on haemoglobin ≥ 9 g/dl, white cell count (WCC) < 0.3 G/l, platelet count <50 G/l and chemotherapy more intensive than acute lymphoblastic leukaemia maintenance therapy) was calculated and AEs were documented. Results: In total, 100 FN episodes occurred in 52 patients, male:female ratio was 1...
November 15, 2017: Journal of Tropical Pediatrics
https://www.readbyqxmd.com/read/29147018/enforced-gfi1-expression-impedes-human-and-murine-leukemic-cell-growth
#5
Judith M Hönes, Aniththa Thivakaran, Lacramioara Botezatu, Pradeep Patnana, Symone Vitoriano da Conceição Castro, Yahya S Al-Matary, Judith Schütte, Karen B I Fischer, Lothar Vassen, André Görgens, Ulrich Dührsen, Bernd Giebel, Cyrus Khandanpour
The differentiation of haematopoietic cells is regulated by a plethora of so-called transcription factors (TFs). Mutations in genes encoding TFs or graded reduction in their expression levels can induce the development of various malignant diseases such as acute myeloid leukaemia (AML). Growth Factor Independence 1 (GFI1) is a transcriptional repressor with key roles in haematopoiesis, including regulating self-renewal of haematopoietic stem cells (HSCs) as well as myeloid and lymphoid differentiation. Analysis of AML patients and different AML mouse models with reduced GFI1 gene expression levels revealed a direct link between low GFI1 protein level and accelerated AML development and inferior prognosis...
November 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29145456/regulation-of-the-bone-marrow-microenvironment-by-g-csf-effects-of-g-csf-on-acute-lymphoblastic-leukaemia
#6
Jordan Basnett, Vicki Xie, Adam Cisterne, Ken Bradstock, Linda Bendall
It has been suggested that disruption of the lymphoid niche by G-CSF may be of therapeutic benefit to patients with acute lymphoblastic leukaemia. We used a xenograft model to determine the effect of G-CSF on ALL progression in a minimal residual disease setting. Consistent with the effects on normal murine B cell progenitors, G-CSF slowed disease in the majority of ALL xenografts tested, suggesting that G-CSF may provide benefits beyond neutrophil recovery for ALL patients. However, two of eight xenografts demonstrated accelerated disease progression...
2017: PloS One
https://www.readbyqxmd.com/read/29144447/bcat1-restricts-%C3%AE-kg-levels-in-aml-stem-cells-leading-to-idhmut-like-dna-hypermethylation
#7
Simon Raffel, Mattia Falcone, Niclas Kneisel, Jenny Hansson, Wei Wang, Christoph Lutz, Lars Bullinger, Gernot Poschet, Yannic Nonnenmacher, Andrea Barnert, Carsten Bahr, Petra Zeisberger, Adriana Przybylla, Markus Sohn, Martje Tönjes, Ayelet Erez, Lital Adler, Patrizia Jensen, Claudia Scholl, Stefan Fröhling, Sibylle Cocciardi, Patrick Wuchter, Christian Thiede, Anne Flörcken, Jörg Westermann, Gerhard Ehninger, Peter Lichter, Karsten Hiller, Rüdiger Hell, Carl Herrmann, Anthony D Ho, Jeroen Krijgsveld, Bernhard Radlwimmer, Andreas Trumpp
The branched-chain amino acid (BCAA) pathway and high levels of BCAA transaminase 1 (BCAT1) have recently been associated with aggressiveness in several cancer entities. However, the mechanistic role of BCAT1 in this process remains largely uncertain. Here, by performing high-resolution proteomic analysis of human acute myeloid leukaemia (AML) stem-cell and non-stem-cell populations, we find the BCAA pathway enriched and BCAT1 protein and transcripts overexpressed in leukaemia stem cells. We show that BCAT1, which transfers α-amino groups from BCAAs to α-ketoglutarate (αKG), is a critical regulator of intracellular αKG homeostasis...
November 16, 2017: Nature
https://www.readbyqxmd.com/read/29136959/alterations-of-biomechanics-in-cancer-and-normal-cells-induced-by-doxorubicin
#8
Kaja Fraczkowska, Marcin Bacia, Magda Przybyło, Dominik Drabik, Aleksandra Kaczorowska, Justyna Rybka, Ewa Stefanko, Slawomir Drobczynski, Jan Masajada, Halina Podbielska, Tomasz Wrobel, Marta Kopaczynska
Mechanical properties of biological structures play an important role in regulating cellular activities and are critical for understanding metabolic processes in cancerous cells and the effects of drugs. For some cancers, such as acute myeloid leukaemia, chemotherapy is one of preferential methods. However, due to the lack of selectivity to cancer cells, cytostatic agents cause toxicity to normal tissues. Here, we study the effect of doxorubicin (DOX) on the mechanical properties of DNA molecules, leukemic blast cells and erythrocytes, using optical tweezers...
November 10, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29134442/endothelial-tnf-%C3%AE-induction-by-hsp60-secreted-from-thp-1-monocytes-exposed-to-hyperglycaemic-conditions
#9
Ryan Dennis Martinus, Julie Goldsbury
A non-resolving inflammation of the endothelium is recognised to be an important process leading to atherosclerosis. In diabetes, this process is thought to account for a significant number of cardiovascular disease-associated death and disability. However, the molecular mechanisms by which diabetes contributes to endothelial inflammation remain to be established. Whilst there is some evidence linking hyperglycaemia-induced reactive oxygen species (ROS) formation by the mitochondrial electron-transport chain to oxidative stress, cellular injury and apoptosis in the endothelium, a clear link to endothelium inflammation has not yet been established...
November 13, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/29129782/reactive-oxygen-species-production-triggers-green-tea-induced-anti-leukaemic-effects-on-acute-promyelocytic-leukaemia-model
#10
Cristiane Okuda Torello, Rodrigo Naoto Shiraishi, Fernanda Isabel Della Via, Tamara Cristina Lopes de Castro, Ana Leda Longhini, Irene Santos, André Luis Bombeiro, Cleide Lúcia Araujo Silva, Mary Luci de Souza Queiroz, Eduardo Magalhães Rego, Sara Teresinha Olalla Saad
Green tea (GT) has been consumed as a beverage for thousands of years because of its therapeutic properties observed over time. Because there is no sufficient evidence supporting the protective role of tea intake during the development of acute myeloid leukaemia, we herein study GT extract effects on an acute promyelocytic leukaemia model. Our results demonstrated that GT reduces leucocytosis and immature cells (blasts) in peripheral blood, bone marrow (BM), and spleen of leukaemic mice, parallel with an increase of mature cells in the BM...
November 10, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29124749/prediction-of-bleeding-and-thrombosis-by-standard-biochemical-coagulation-variables-in-haematological-intensive-care-patients
#11
L Russell, M B Madsen, M Dahl, P Kampmann, A Perner
PURPOSE: We assessed the value of standard biochemical coagulation parameters in predicting bleeding, thrombosis and mortality in adult Intensive Care Unit (ICU) patients with haematological malignancies. METHODS: We screened all patients with acute leukaemia and myelodysplastic syndrome admitted to a university hospital ICU during 2008-2012. Data were obtained from the clinical chemistry laboratory database and patient files. We graded bleeding according to the World Health Organisation (WHO)-system within 24-h, within 5-days and during the whole ICU stay...
November 9, 2017: Acta Anaesthesiologica Scandinavica
https://www.readbyqxmd.com/read/29122897/polymyalgia-rheumatica-development-in-a-patient-under-pi3k-inhibitor-therapy-for-chronic-lymphocytic-leukaemia
#12
Sanah Sajawal, Sarah L Mackie, Peter Hillmen, Dennis McGonagle
We report a patient with chronic lymphocytic leukaemia (CLL) who was treated with idelalisib, a PI3Kδ inhibitor with rituximab. After 20 weeks of treatment, the patient developed classical signs and symptoms of polymyalgia rheumatica (PMR) in association with an elevated C reactive protein of 74 mg/L. After 2 weeks of prednisolone 15 mg daily symptoms had resolved and acute phase markers normalised. To our knowledge, this is the first report of PMR developing as a complication of PI3Kδ inhibitor treatment of CLL...
November 8, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/29120027/humanised-mouse-models-for-haematopoiesis-and-infectious-diseases
#13
Veronika Lysenko, Donal McHugh, Lena Behrmann, Mary-Aude Rochat, Christian Matthias Wilk, Larisa Kovtonyuk, Jean-Pierre Bourquin, Christian Münz, Markus Gabriel Manz, Roberto Speck, Alexandre Theocharides
"Humanised" mouse models have emerged over past years as powerful tools for investigating human haematopoiesis and immunity. They allowed the identification of key factors for the maintenance and function of normal and leukaemic human haematopoietic stem cells. These findings have been widely used to dissect the pathogenesis of multiple myeloid and lymphoid neoplasms, such as acute myeloid leukaemia and acute lymphoblastic leukaemia. Furthermore, these models can serve as a stepping-stone to clinical trials by testing novel drugs that target leukaemic stem cells...
November 9, 2017: Swiss Medical Weekly
https://www.readbyqxmd.com/read/29115416/annexin-a2-and-cancer-a-systematic-review
#14
Maria V Christensen, Claus K Høgdall, Kirsten M Jochumsen, Estrid V S Høgdall
Annexin A2 is a 36-kDa protein interfering with multiple cellular processes especially in cancer progression. The present review aimed to show the relations between Annexin A2 and cancer. A systematic search for studies investigating cancer and Annexin A2 expression was conducted using PubMed. Acute lymphoblastic leukaemia, acute promyelocytic leukaemia, clear cell renal cell carcinoma, breast, cervical, colorectal, endometrial, gastric cancer, glioblastoma, hepatocellular carcinoma, lung, multiple myeloma, oesophageal squamous cell carcinoma, ovarian cancer, pancreatic duct adenocarcinoma, prostate cancer and urothelial carcinoma were evaluated...
November 8, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29113504/enhancement-of-chemosensitivity-by-simultaneously-silencing-of-mcl-1-and-survivin-genes-using-small-interfering-rna-in-human-myelomonocytic-leukaemia
#15
Mahdi Jafarlou, Dariush Shanehbandi, Parvin Dehghan, Behzad Mansoori, F Othman, Behzad Baradaran
Acute myeloid leukaemia (AML) is a genetically heterogeneous, severe and rapidly progressing disease triggered by blocking granulocyte or monocyte differentiation and maturation. Overexpression of myeloid cell leukaemia-1 (Mcl-1) and Survivin is associated with drug resistance, tumour progression and inhibition of apoptotic mechanisms in leukaemia and several cancers. In the present study, we examined the combined effect of etoposide and dual siRNA-mediated silencing of Mcl-1 and Survivin on U-937 AML cells...
November 7, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/29106702/hypothalamic-pituitary-adrenal-hpa-axis-suppression-after-treatment-with-glucocorticoid-therapy-for-childhood-acute-lymphoblastic-leukaemia
#16
REVIEW
Niki Rensen, Reinoud Jbj Gemke, Elvira C van Dalen, Joost Rotteveel, Gertjan Jl Kaspers
BACKGROUND: Glucocorticoids play a major role in the treatment of acute lymphoblastic leukaemia (ALL). However, supraphysiological doses can suppress the hypothalamic-pituitary-adrenal (HPA) axis. HPA axis suppression resulting in reduced cortisol response may cause an impaired stress response and an inadequate host defence against infection, which remain a cause of morbidity and death. Suppression commonly occurs in the first days after cessation of glucocorticoid therapy, but the exact duration is unclear...
November 6, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/29102721/cellular-immunotherapy-for-haematological-malignancies-beyond-bone-marrow-transplant
#17
REVIEW
Melita Cirillo, Peter Tan, Marian Sturm, Catherine Cole
Immunotherapy has changed treatment practices for many haematological malignancies. Despite the current era of targeted therapy, chemotherapy remains the backbone of treatment for many haematological malignancies, especially in acute leukaemia, where relapse remains the major cause of mortality. Application of novel immunotherapies in haematology attempts to harness the killing power of the immune system against leukaemia and lymphoma. Cellular immunotherapy is evolving rapidly for high risk haematological disorders...
November 1, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29101342/a-protease-resistant-escherichia-coli-asparaginase-with-outstanding-stability-and-enhanced-anti-leukaemic-activity-in-vitro
#18
Maristella Maggi, Steven D Mittelman, Jean Hugues Parmentier, Giorgio Colombo, Massimiliano Meli, Jeannette Marie Whitmire, D Scott Merrell, Julian Whitelegge, Claudia Scotti
L-Asparaginases (ASNases) have been used as first line drugs for paediatric Acute Lymphoblastic Leukaemia (ALL) treatment for more than 40 years. Both the Escherichia coli (EcAII) and Erwinia chrysanthemi (ErAII) type II ASNases currently used in the clinics are characterized by high in vivo instability, short half-life and the requirement of several administrations to obtain a pharmacologically active concentration. Moreover, they are sensitive to proteases (cathepsin B and asparagine endopeptidase) that are over-expressed by resistant leukaemia lymphoblasts, thereby impairing drug activity and pharmacokinetics...
November 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29098953/efficacy-of-clara-in-recurrent-refractory-acute-myeloid-leukaemia-patients-unresponsive-to-flag-chemotherapy
#19
Ali Hakan Kaya, Emre Tekgündüz, Kadir Ilkkiliç, Mehmet Sinan Dal, Alparslan Merdin, Abdullah Karakus, Sibel Kabukcu Hacioglu, Filiz Bekdemir, Merih Kızıl Çakar, Mehmet Hilmi Dogu, Mehmet Orhan Ayyildiz, Serdal Korkmaz, Fevzi Altuntaş
We hereby report our multicentre, retrospective experience with CLARA in patients with fludarabine/cytarabine/G-CSF (FLAG) refractory AML. The study included all consecutive R/R AML patients, who received CLARA salvage during October 2010-October 2015 period. All patients were unresponsive to FLAG salvage chemotherapy regimen and did not undergo previous allo-HCT. A total of 40 patients were included. Following CLARA 5 (12.5%) patients experienced induction mortality and 10 (25%) patients achieved CR. 25 (62...
November 3, 2017: Journal of Chemotherapy
https://www.readbyqxmd.com/read/29095161/structure-and-function-of-the-thermostable-l-asparaginase-from-thermococcus-kodakarensis
#20
Jingxu Guo, Alun R Coker, Steve P Wood, Jonathan B Cooper, Shahid Mahmood Chohan, Naeem Rashid, Muhummad Akhtar
L-Asparaginases catalyse the hydrolysis of asparagine to aspartic acid and ammonia. In addition, L-asparaginase is involved in the biosynthesis of amino acids such as lysine, methionine and threonine. These enzymes have been used as chemotherapeutic agents for the treatment of acute lymphoblastic leukaemia and other haematopoietic malignancies since the tumour cells cannot synthesize sufficient L-asparagine and are thus killed by deprivation of this amino acid. L-Asparaginases are also used in the food industry and have potential in the development of biosensors, for example for asparagine levels in leukaemia...
November 1, 2017: Acta Crystallographica. Section D, Structural Biology
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