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Acute myeloid leukaemia

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https://www.readbyqxmd.com/read/28216661/mir-194-5p-bclaf1-deregulation-in-aml-tumorigenesis
#1
C Dell'Aversana, C Giorgio, L D'Amato, G Lania, F Matarese, S Saeed, A Di Costanzo, V B Petrizzi, C Ingenito, J H A Martens, I Pallavicini, S Minucci, A Carissimo, H G Stunnenberg, L Altucci
Deregulation of epigenetic mechanisms, including miRNA, contributes to leukaemogenesis and drug resistance by interfering with cancer-specific molecular pathways. Here, we show that the balance between miR-194-5p and its newly discovered target BCL2-associated transcription factor 1 (BCLAF1) regulates differentiation and survival of normal haematopoietic progenitors. In acute myeloid leukaemias (AMLs) this balance is perturbed, locking cells into an immature, potentially 'immortal' state. Enhanced expression of miR-194-5p by treatment with the HDAC inhibitor SAHA or by exogenous miR-194-5p expression re-sensitizes cells to differentiation and apoptosis by inducing BCLAF1 to shuttle between nucleus and cytosol...
February 20, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28212292/azacitidine-for-front-line-therapy-of-patients-with-aml-reproducible-efficacy-established-by-direct-comparison-of-international-phase-3-trial-data-with-registry-data-from-the-austrian-azacitidine-registry-of-the-agmt-study-group
#2
Lisa Pleyer, Hartmut Döhner, Hervé Dombret, John F Seymour, Andre C Schuh, C L Beach, Arlene S Swern, Sonja Burgstaller, Reinhard Stauder, Michael Girschikofsky, Heinz Sill, Konstantin Schlick, Josef Thaler, Britta Halter, Sigrid Machherndl Spandl, Armin Zebisch, Angelika Pichler, Michael Pfeilstöcker, Eva M Autzinger, Alois Lang, Klaus Geissler, Daniela Voskova, Wolfgang R Sperr, Sabine Hojas, Inga M Rogulj, Johannes Andel, Richard Greil
We recently published a clinically-meaningful improvement in median overall survival (OS) for patients with acute myeloid leukaemia (AML), >30% bone marrow (BM) blasts and white blood cell (WBC) count ≤15 G/L, treated with front-line azacitidine versus conventional care regimens within a phase 3 clinical trial (AZA-AML-001; NCT01074047; registered: February 2010). As results obtained in clinical trials are facing increased pressure to be confirmed by real-world data, we aimed to test whether data obtained in the AZA-AML-001 trial accurately represent observations made in routine clinical practice by analysing additional AML patients treated with azacitidine front-line within the Austrian Azacitidine Registry (AAR; NCT01595295; registered: May 2012) and directly comparing patient-level data of both cohorts...
February 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28209647/striae-gravidarum-leukaemia-cutis-a-rare-manifestation-of-acute-myeloid-leukaemia
#3
Mahmoud H Ayesh Haj Yousef, M Untaser M Omari, Mo'ath M Rjoub, Sohaib M Al-Khatib
No abstract text is available yet for this article.
February 16, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28198173/delphi-based-study-and-analysis-of-key-risk-factors-for-invasive-fungal-infection-in-haematological-patients
#4
L Vázquez, M Salavert, J Gayoso, M Lizasoaín, I Ruiz Camps, N Di Benedetto
OBJECTIVE: Mortality caused by invasive fungal infections due to filamentous fungi (IFI-FF) is high. Predisposing factors to IFI-FF are multiple and should be stratified. The objective of this study was to identify key risk factors for IFI-FF in onco-haematological patients in different clinical settings. METHODS: Prospective national Delphi study. Risk factors for IFI-FF in patients with onco-haematological diseases were identified by a systematic review of the literature...
February 14, 2017: Revista Española de Quimioterapia: Publicación Oficial de la Sociedad Española de Quimioterapia
https://www.readbyqxmd.com/read/28196450/a-review-of-therapy-related-myelodysplastic-syndromes-and-acute-myeloid-leukaemia-t-mds-aml-in-irish-patients-a-single-centre-experience
#5
Su W Maung, Cathie Burke, Jennifer Hayde, Janice Walshe, Ray McDermott, Ronan Desmond, Johnny McHugh, Helen Enright
OBJECTIVES: To demonstrate the incidence, characteristics, treatment and outcomes of patients with therapy-related myelodysplastic syndromes and therapy-related acute myeloid leukaemia (t-MDS/AML) in a tertiary referral centre. METHODS: Patients meeting the diagnostic criteria for t-MDS/AML from 2003 to 2014 were reviewed to analyse their diagnostic features, details of antecedent disorder and treatment, approach to management and survival. RESULTS: 39 patients who developed t-MDS/AML were identified with incidence of 8...
February 15, 2017: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/28192788/metabolic-gatekeeper-function-of-b-lymphoid-transcription-factors
#6
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/28182813/second-malignant-neoplasms-in-childhood-cancer-survivors-treated-in-a-tertiary-paediatric-oncology-centre
#7
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/28168755/palbociclib-can-overcome-mutations-in-cyclin-dependent-kinase-6-that-break-hydrogen-bonds-between-the-drug-and-the-protein
#8
Stella Hernandez Maganhi, Patrizia Jensen, Ignez Caracelli, Julio Zukerman Schpector, Stefan Fröhling, Ran Friedman
Inhibition of cyclin dependent kinases (CDKs) 4 and 6 prevent cells from entering the synthesis phase of the cell cycle. CDK4 and 6 are therefore important drug targets in various cancers. The selective CDK4/6 inhibitor palbociclib is approved for the treatment of breast cancer and has shown activity in a cellular model of mixed lineage leukaemia (MLL)-rearranged acute myeloid leukaemia (AML). We studied the interactions of palbociclib and CDK6 using molecular dynamics simulations. Analysis of the simulations suggested several interactions that stabilised the drug in its binding site and that were not observed in the crystal structure of the protein-drug complex...
February 7, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28162984/eltrombopag-versus-placebo-for-low-risk-myelodysplastic-syndromes-with-thrombocytopenia-eqol-mds-phase-1-results-of-a-single-blind-randomised-controlled-phase-2-superiority-trial
#9
Esther N Oliva, Caterina Alati, Valeria Santini, Antonella Poloni, Alfredo Molteni, Pasquale Niscola, Flavia Salvi, Grazia Sanpaolo, Enrico Balleari, Ulrich Germing, Pierre Fenaux, Aspasia Stamatoullas, Giuseppe A Palumbo, Prassede Salutari, Stefana Impera, Paolo Avanzini, Agostino Cortelezzi, Anna Marina Liberati, Paola Carluccio, Francesco Buccisano, Maria Teresa Voso, Stefano Mancini, Austin Kulasekararaj, Fortunato Morabito, Monica Bocchia, Patrizia Cufari, Maria Antonietta Aloe Spiriti, Irene Santacaterina, Maria Grazia D'Errigo, Irene Bova, Gina Zini, Roberto Latagliata
BACKGROUND: In myelodysplastic syndromes, thrombocytopenia is associated with mortality, but treatments in this setting are scarce. We tested whether eltrombopag, a thrombopoietin receptor agonist, might be effective in improving thrombocytopenia in lower-risk myelodysplastic syndromes and severe thrombocytopenia. METHODS: EQoL-MDS was a single-blind, randomised, controlled, phase 2 superiority trial of adult patients with low-risk or International Prognostic Scoring System intermediate-1-risk myelodysplastic syndromes and severe thrombocytopenia...
February 2, 2017: Lancet Haematology
https://www.readbyqxmd.com/read/28153669/coffee-and-tea-consumption-and-risk-of-leukaemia-in-an-adult-population-a-reanalysis-of-the-italian-multicentre-case-control-study
#10
Stefano Parodi, Domenico Franco Merlo, Emanuele Stagnaro
BACKGROUND: Coffee and tea are the most frequently consumed beverages in the world. Their potential effect on the risk of developing different types of malignancies has been largely investigated, but studies on leukaemia in adults are scarce. METHODS: The present investigation is aimed at evaluating the potential role of regular coffee and tea intake on the risk of adult leukaemia by reanalysing a large population based case-control study carried out in Italy, a country with a high coffee consumption and a low use of green tea...
January 30, 2017: Cancer Epidemiology
https://www.readbyqxmd.com/read/28146632/antibody-targeted-cyclodextrin-based-nanoparticles-for-sirna-delivery-in-the-treatment-of-acute-myeloid-leukemia-physicochemical-characteristics-in-vitro-mechanistic-studies-and-ex-vivo-patient-derived-therapeutic-efficacy
#11
Jianfeng Guo, Eileen G Russell, Raphael Darcy, Thomas G Cotter, Sharon L McKenna, Mary R Cahill, Caitriona M O'Driscoll
Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults and is associated with high relapse rates. It is known that leukemia stem cells (LSCs), a very small subpopulation of the total number of leukemic cells, maintain the leukemia phenotype (∼80-90% of AML remain the same as at first diagnosis), display chemotherapy resistance, and contribute to disease regeneration. Therefore, targeting LSCs could control the relapse of AML. Small interfering RNA (siRNA), an effector of the RNA interference (RNAi) pathway, can selectively downregulate any gene implicated in the pathology of disease, presenting great potential for treatment of AML...
February 14, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28146265/m-tor-inhibitors-and-their-potential-role-in-haematological-malignancies
#12
REVIEW
Teresa Calimeri, Andrés J M Ferreri
It is widely demonstrated that the PI3K-AKT-mTOR signalling is critical in normal myeloid and lymphoid development and function. Thus, it is not strange that this pathway is often deregulated in haematological tumours, providing a strong preclinical rationale for the use of drugs targeting the PI3K-AKT-mTOR axis in haematological malignancies. The main focus of this review is to examine the mammalian target of rapamycin (mTOR, also termed mechanistic target of rapamycin [MTOR]) signalling pathways and to provide a brief overview of rapalogs and second-generation mTOR inhibitors used to target its aberrant activation in cancer treatment...
February 1, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28144286/study-of-clinical-haematological-and-cytogenetic-profile-of-patients-with-acute-erythroid-leukaemia
#13
Jacob Abraham Linu, Ms Namratha Udupa, D S Madhumathi, K C Lakshmaiah, K Govind Babu, D Lokanatha, Mc Suresh Babu, K N Lokesh, L K Rajeev, A H Rudresha
BACKGROUND: Acute erythroid leukaemia (AEL) is a rare subtype of acute myeloid leukaemia (AML), constituting <5% of all the cases of AML. The World Health Organization (WHO) in 2001 classified AEL into two types: (1) erythroid/myeloid leukaemia which required ≥50% erythroid precursors with ≥20% of the non-erythroid cells to be myeloid blasts and (2) pure erythroleukemia (pEL) with ≥80% erythroblasts. The WHO 2008 classification kept these subcategories, but made erythroleukemia a diagnosis of exclusion...
2017: Ecancermedicalscience
https://www.readbyqxmd.com/read/28134024/diagnosis-in-subdural-myeloid-sarcoma
#14
Alan Lackey, Barbara Laing, Andrew Perkins, Michael Bryant
Introduction A 74-year-old man presented to hospital with a headache, thrombocytopaenia and an acute deterioration in cognition on a background of acute monocytic leukaemia in remission. Method This is a case report with computed tomography (CT), magnetic resonance (MR) and histopathology imaging. Results Preoperative CT and limited MR demonstrated a subdural lesion with marked midline shift. Craniotomy performed for evacuation of the presumed subdural haematoma revealed a solid tumour-like lesion. Histopathology identified the presence of a myeloid sarcoma (chloroma)...
January 1, 2017: Neuroradiology Journal
https://www.readbyqxmd.com/read/28128441/restrictive-versus-liberal-red-blood-cell-transfusion-strategies-for-people-with-haematological-malignancies-treated-with-intensive-chemotherapy-or-radiotherapy-or-both-with-or-without-haematopoietic-stem-cell-support
#15
REVIEW
Lise J Estcourt, Reem Malouf, Marialena Trivella, Dean A Fergusson, Sally Hopewell, Michael F Murphy
BACKGROUND: Many people diagnosed with haematological malignancies experience anaemia, and red blood cell (RBC) transfusion plays an essential supportive role in their management. Different strategies have been developed for RBC transfusions. A restrictive transfusion strategy seeks to maintain a lower haemoglobin level (usually between 70 g/L to 90 g/L) with a trigger for transfusion when the haemoglobin drops below 70 g/L), whereas a liberal transfusion strategy aims to maintain a higher haemoglobin (usually between 100 g/L to 120 g/L, with a threshold for transfusion when haemoglobin drops below 100 g/L)...
January 27, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28111469/clinical-relevance-of-failed-and-missing-cytogenetic-analysis-in-acute-myeloid-leukaemia-aml
#16
L Chilton, C J Harrison, I Ashworth, D Murdy, A K Burnett, D Grimwade, A V Moorman, R K Hills
Leukemia accepted article preview online, 23 January 2017. doi:10.1038/leu.2017.37.
January 23, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28109554/clinical-and-microbiological-characteristics-of-bloodstream-infections-among-patients-with-haematological-malignancies-with-and-without-neutropenia-at-a-medical-centre-in-northern-taiwan-2008-2013
#17
Chien-Yuan Chen, Feng-Ming Tien, Wang-Huei Sheng, Shang-Yi Huang, Ming Yao, Jih-Luh Tang, Woei Tsay, Hwei-Fang Tien, Po-Ren Hsueh
This study aimed to investigate the epidemiology and microbiology of bloodstream infections (BSIs) in patients with haematological malignancies. Clinical characteristics and microbiology of 2083 patients with haematological malignancy who were treated for BSI from 2008 to 2013 at a medical centre in Taiwan were retrospectively reviewed. Lymphoma (38.1%) was the most common, followed by acute myeloid leukaemia (30.9%). Of the 2090 non-duplicate BSI isolates, 1310 (62.7%) were recovered from patients with neutropenia...
January 3, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28101592/long-term-safety-and-outcome-of-fludarabine-cyclophosphamide-and-mitoxantrone-fcm-regimen-in-previously-untreated-patients-with-advanced-follicular-lymphoma-12%C3%A2-years-follow-up-of-a-phase-2-trial
#18
Laura Magnano, Silvia Montoto, Eva González-Barca, Javier Briones, Juan Manuel Sancho, Ana Muntañola, Antonio Salar, Joan Besalduch, Lourdes Escoda, Carol Moreno, Eva Domingo-Domenech, Cristina Estany, Albert Oriol, Albert Altés, Carmen Pedro, Santiago Gardella, Antoni Asensio, Pilar Vivancos, Alberto Fernández de Sevilla, Josep María Ribera, Dolors Colomer, Elias Campo, Armando López-Guillermo
Fludarabine combinations are very affective in follicular lymphoma (FL) with high rates of complete response and prolonged survival. However, late toxicities could be a concern. The aim of the present study was to analyze the long-term impact on survival, relapse and late toxicities of a trial of treatment with fludarabine, mitoxantrone and cyclophosphamide (FCM regimen) for untreated patients with advanced stage FL. One hundred and twenty patients enrolled in a phase 2 trial of treatment with FCM regimen between 2000 and 2003 were evaluated...
January 18, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28100593/clinical-implications-of-dnmt3a-mutations-in-a-southeast-asian-cohort-of-acute-myeloid-leukaemia-patients
#19
Marcus Tan, Isaac K S Ng, Zhaojin Chen, Kenneth Ban, Christopher Ng, Lily Chiu, Elaine Seah, Mingxuan Lin, Bee Choo Tai, Benedict Yan, Chin Hin Ng, Wee-Joo Chng
AIMS: In recent years, genomic technologies have enabled the identification of mutations in acute myeloid leukaemia (AML). DNMT3A is a recurrently mutated epigenetic modifier gene in AML. To date, the prognostic significance of DNMT3A mutations has not been studied in a Southeast Asian AML population. We sought to investigate the clinical implications of DNMT3A mutations in a Southeast Asian cohort of AML patients. METHODS: DNMT3A mutations were identified using a targeted next-generation sequencing panel in 157 AML patients...
January 18, 2017: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28100265/allogeneic-stem-cell-transplantation-in-adult-patients-with-acute-myeloid-leukaemia-and-17p-abnormalities-in-first-complete-remission-a-study-from-the-acute-leukemia-working-party-alwp-of-the-european-society-for-blood-and-marrow-transplantation-ebmt
#20
Xavier Poiré, Myriam Labopin, Johan Maertens, Ibrahim Yakoub-Agha, Didier Blaise, Norbert Ifrah, Gérard Socié, Tobias Gedde-Dhal, Nicolaas Schaap, Jan J Cornelissen, Stéphane Vigouroux, Jaime Sanz, Lucienne Michaux, Jordi Esteve, Mohamad Mohty, Arnon Nagler
BACKGROUND: Acute myeloid leukaemia (AML) with 17p abnormalities (abn(17p)) carries a very poor prognosis due to high refractoriness to conventional chemotherapy, and allogeneic stem cell transplantation (allo-SCT) appears as the only potential curative option. METHODS: To address outcomes after allo-SCT in patients with abn(17p), we retrospectively analysed de novo or secondary AML undergoing SCT between 2000 and 2013 from the EBMT registry. RESULTS: One hundred thirty-nine patients with confirmed abn(17p) have been selected...
January 18, 2017: Journal of Hematology & Oncology
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