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Acute myeloid leukaemia

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https://www.readbyqxmd.com/read/28329763/the-allosteric-inhibitor-abl001-enables-dual-targeting-of-bcr-abl1
#1
Andrew A Wylie, Joseph Schoepfer, Wolfgang Jahnke, Sandra W Cowan-Jacob, Alice Loo, Pascal Furet, Andreas L Marzinzik, Xavier Pelle, Jerry Donovan, Wenjing Zhu, Silvia Buonamici, A Quamrul Hassan, Franco Lombardo, Varsha Iyer, Michael Palmer, Giuliano Berellini, Stephanie Dodd, Sanjeev Thohan, Hans Bitter, Susan Branford, David M Ross, Timothy P Hughes, Lilli Petruzzelli, K Gary Vanasse, Markus Warmuth, Francesco Hofmann, Nicholas J Keen, William R Sellers
Chronic myeloid leukaemia (CML) is driven by the activity of the BCR-ABL1 fusion oncoprotein. ABL1 kinase inhibitors have improved the clinical outcomes for patients with CML, with over 80% of patients treated with imatinib surviving for more than 10 years. Second-generation ABL1 kinase inhibitors induce more potent molecular responses in both previously untreated and imatinib-resistant patients with CML. Studies in patients with chronic-phase CML have shown that around 50% of patients who achieve and maintain undetectable BCR-ABL1 transcript levels for at least 2 years remain disease-free after the withdrawal of treatment...
March 22, 2017: Nature
https://www.readbyqxmd.com/read/28324282/recurrent-bowel-blood-translocations-of-escherichia-coli-with-the-unique-virulence-characteristics-over-three-year-period-in-the-patient-with-acute-myeloid-leukaemia-case-report
#2
Beata Krawczyk, Anna Śledzińska, Agnieszka Piekarska, Andrzej Hellmann, Józef Kur
In patients with haematological malignancies, the bowel remains the main source of Escherichia coli bloodstream infections. We present the clinical example of recurrent bowel-blood translocations of E. coli with the unique virulence characteristics in a 55-year-old male with the diagnosis of acute myeloid leukaemia. The virulent factors profile of examined strains confirmed that the co-existence of genes papC, sfa, usp and cnf1, encoding virulence factors, predisposes E. coli to translocation from the gastrointestinal tract to the vascular bed...
March 21, 2017: Journal of Applied Genetics
https://www.readbyqxmd.com/read/28322129/including-historical-data-in-the-analysis-of-clinical-trials-is-it-worth-the-effort
#3
Joost van Rosmalen, David Dejardin, Yvette van Norden, Bob Löwenberg, Emmanuel Lesaffre
Data of previous trials with a similar setting are often available in the analysis of clinical trials. Several Bayesian methods have been proposed for including historical data as prior information in the analysis of the current trial, such as the (modified) power prior, the (robust) meta-analytic-predictive prior, the commensurate prior and methods proposed by Pocock and Murray et al. We compared these methods and illustrated their use in a practical setting, including an assessment of the comparability of the current and the historical data...
January 1, 2017: Statistical Methods in Medical Research
https://www.readbyqxmd.com/read/28318761/the-bone-marrow-microenvironment-home-of-the-leukemic-blasts
#4
REVIEW
Manar S Shafat, Bruno Gnaneswaran, Kristian M Bowles, Stuart A Rushworth
Acute Myeloid Leukaemia (AML) is a genetically, biologically and clinically heterogeneous set of diseases, which are characterised by an increased growth of abnormal myeloid progenitor cells within the bone marrow (BM). Ex-vivo AML exhibits a high level of spontaneous apoptosis. Furthermore, relapse for patients achieving remission occurs from minimal residual disease harboured within the BM microenvironment. Taken together, these observations illustrate the importance of the BM microenvironment in sustaining AML...
March 12, 2017: Blood Reviews
https://www.readbyqxmd.com/read/28303892/how-good-are-we-at-predicting-the-fate-of-someone-with-acute-myeloid-leukaemia
#5
EDITORIAL
E Estey, R P Gale
No abstract text is available yet for this article.
March 17, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28286768/epigenetic-guardian-a-review-of-the-dna-methyltransferase-dnmt3a-in-acute-myeloid-leukaemia-and-clonal-haematopoiesis
#6
REVIEW
Sabah F Chaudry, Timothy J T Chevassut
Acute myeloid leukaemia (AML) is a haematological malignancy characterized by clonal stem cell proliferation and aberrant block in differentiation. Dysfunction of epigenetic modifiers contributes significantly to the pathogenesis of AML. One frequently mutated gene involved in epigenetic modification is DNMT3A (DNA methyltransferase-3-alpha), a DNA methyltransferase that alters gene expression by de novo methylation of cytosine bases at CpG dinucleotides. Approximately 22% of AML and 36% of cytogenetically normal AML cases carry DNMT3A mutations and around 60% of these mutations affect the R882 codon...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28281897/patients-with-acute-myeloid-leukemia-can-be-subclassified-based-on-the-constitutive-cytokine-release-of-the-leukemic-cells-the-possible-clinical-relevance-and-the-importance-of-cellular-iron-metabolism
#7
Annette K Brenner, Tor Henrik Anderson Tvedt, Ina Nepstad, Kristin P Rye, Karen M Hagen, Håkon Reikvam, Øystein Bruserud
OBJECTIVE: Acute myeloid leukaemia (AML) is a heterogeneous malignancy; we studied how the constitutive cytokine release by the AML cells varies among patients. METHODS: We investigated the constitutive release of 28 mediators during in vitro culture for 79 consecutive patients. RESULTS: Constitutive cytokine release profiles differed among patients, and hierarchical clustering identified three subsets with high, intermediate and low release, respectively...
April 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28273186/-acute-myeloid-leukaemia-in-adults-therapeutic-possibilities-today-and-new-agents-in-the-future
#8
Ilona Tárkányi
Advances in the treatment of acute myeloid leukaemia are still modest. Through emerging knowledge in molecular genetics we gain new insights into the pathogenesis of the disease. The first targeted therapies have emerged, but failed to show a breakthrough effect. The outcome of standard chemotherapy has improved due to improvements in supportive care and slight modifications in the protocols, but we still hope to augment the results of intensive chemotherapy applied in our young and fit patients, by adding targeted therapeutic agents...
March 8, 2017: Magyar Onkologia
https://www.readbyqxmd.com/read/28259884/the-dicentric-chromosome-dic-20-22-is-a-recurrent-abnormality-in-myelodysplastic-syndromes-and-is-a-product-of-telomere-fusion
#9
Ruth N MacKinnon, Hendrika M Duivenvoorden, Lynda J Campbell, Meaghan Wall
We describe a recurrent dicentric chromosome formed by telomere fusion between chromosome 20 and chromosome 22 in 4 cases of myelodysplastic syndromes (MDS) or acute myeloid leukaemia (AML). In particular, the presence of residual telomere sequences at the site of translocation in 3 of the 4 cases makes a compelling case for telomere fusion. This is the first description of a recurrent telomere fusion event in any malignant condition. The 20q subtelomeric region was retained in all 4 examples despite deletion of the 20q12 region closer to the centromere...
March 4, 2017: Cytogenetic and Genome Research
https://www.readbyqxmd.com/read/28246114/intussusception-a-rare-complication-in-a-patient-with-acute-leukaemia-after-consolidation-chemotherapy
#10
REVIEW
Ayman Qasrawi, Mouhanna Abu Ghanimeh, Omar Abughanimeh, Abdulraheem Qasem
Intussusception is telescoping of one segment of the gastrointestinal tract into an adjacent one. It is more common in children than adults. When it occurs in adults, it is usually associated with a lead point. Intussusception is very rare in acute leukaemia and has only been reported in few cases. We present a case of an adult woman who presented with intussusception after a cycle of consolidation chemotherapy with high-dose cytarabine for acute myeloid leukaemia. Other causes of acute abdominal pain were excluded, and the diagnosis was established by CT scan of the abdomen and barium enema...
February 28, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28241141/enl-links-histone-acetylation-to-oncogenic-gene-expression-in-acute-myeloid-leukaemia
#11
Liling Wan, Hong Wen, Yuanyuan Li, Jie Lyu, Yuanxin Xi, Takayuki Hoshii, Julia K Joseph, Xiaolu Wang, Yong-Hwee E Loh, Michael A Erb, Amanda L Souza, James E Bradner, Li Shen, Wei Li, Haitao Li, C David Allis, Scott A Armstrong, Xiaobing Shi
Cancer cells are characterized by aberrant epigenetic landscapes and often exploit chromatin machinery to activate oncogenic gene expression programs. Recognition of modified histones by 'reader' proteins constitutes a key mechanism underlying these processes; therefore, targeting such pathways holds clinical promise, as exemplified by the development of bromodomain and extra-terminal (BET) inhibitors. We recently identified the YEATS domain as an acetyl-lysine-binding module, but its functional importance in human cancer remains unknown...
March 9, 2017: Nature
https://www.readbyqxmd.com/read/28240765/prognostic-significance-of-flow-cytometry-evaluation-of-minimal-residual-disease-in-children-with-acute-myeloid-leukaemia-treated-according-to-the-aieop-aml-2002-01-study-protocol
#12
Barbara Buldini, Frida Rizzati, Riccardo Masetti, Franca Fagioli, Giuseppe Menna, Concetta Micalizzi, Maria Caterina Putti, Carmelo Rizzari, Nicola Santoro, Marco Zecca, Silvia Disarò, Roberto Rondelli, Pietro Merli, Martina Pigazzi, Andrea Pession, Franco Locatelli, Giuseppe Basso
In children with acute myeloid leukaemia (AML), assessment of initial treatment response is an essential prognostic factor; methods more sensitive than morphology are still under evaluation. We report on the measurement of minimal residual disease (MRD), by multicolour flow-cytometry in one centralized laboratory, in 142 children with newly diagnosed AML enrolled in the Associazione Italiana di EmatoOncologia Pediatrica-AML 2002/01 trial. At the end of the first induction course, MRD was <0·1% in 69, 0·1-1% in 16 and >1% in 51 patients...
February 27, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28216661/mir-194-5p-bclaf1-deregulation-in-aml-tumorigenesis
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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