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https://www.readbyqxmd.com/read/28653617/replication-study-inhibition-of-bet-recruitment-to-chromatin-as-an-effective-treatment-for-mll-fusion-leukaemia
#1
Xiaochuan Shan, Juan Jose Fung, Alan Kosaka, Gwenn Danet-Desnoyers
In 2015, as part of the Reproducibility Project: Cancer Biology, we published a Registered Report (Fung et al., 2015), that described how we intended to replicate selected experiments from the paper "Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia" (Dawson et al., 2011). Here, we report the results of those experiments. We found treatment of MLL-fusion leukaemia cells (MV4;11 cell line) with the BET bromodomain inhibitor I-BET151 resulted in selective growth inhibition, whereas treatment of leukaemia cells harboring a different oncogenic driver (K-562 cell line) did not result in selective growth inhibition; this is similar to the findings reported in the original study (Figure 2A and Supplementary Figure 11A,B; Dawson et al...
June 27, 2017: ELife
https://www.readbyqxmd.com/read/28653397/acute-myeloid-leukaemia-genomics
#2
REVIEW
Michael Medinger, Jakob R Passweg
Acute myeloid leukaemia (AML) is a biologically complex, molecularly and clinically heterogeneous disease. Despite major advances in understanding the genetic landscape of AML and its impact on the pathophysiology and biology of the disease, standard treatment options have not significantly changed during the past three decades. AML is characterized by multiple somatically acquired mutations that affect genes of different functional categories. Mutations in genes encoding epigenetic modifiers, such as DNMT3A, ASXL1, TET2, IDH1, and IDH2, are commonly acquired early and are present in the founding clone...
June 27, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28650854/recent-developments-in-deuterium-oxide-tracer-approaches-to-measure-rates-of-substrate-turnover-implications-for-protein-lipid-and-nucleic-acid-research
#3
Matthew S Brook, Daniel J Wilkinson, Philip J Atherton, Ken Smith
PURPOSE OF REVIEW: Methods that inform on dynamic metabolism that can be applied to clinical populations to understand disease progression and responses to therapeutic interventions are of great importance. This review perspective will highlight recent advances, development, and applications of the multivalent stable isotope tracer deuterium oxide (D2O) to the study of substrate metabolism with particular reference to protein, lipids, and nucleic acids, and how these methods can be readily applied within clinical and pharmaceutical research...
June 24, 2017: Current Opinion in Clinical Nutrition and Metabolic Care
https://www.readbyqxmd.com/read/28650479/aml1-eto-requires-enhanced-c-d-box-snorna-rnp-formation-to-induce-self-renewal-and-leukaemia
#4
Fengbiao Zhou, Yi Liu, Christian Rohde, Cornelius Pauli, Dennis Gerloff, Marcel Köhn, Danny Misiak, Nicole Bäumer, Chunhong Cui, Stefanie Göllner, Thomas Oellerich, Hubert Serve, Maria-Paz Garcia-Cuellar, Robert Slany, Jaroslaw P Maciejewski, Bartlomiej Przychodzen, Barbara Seliger, Hans-Ulrich Klein, Christoph Bartenhagen, Wolfgang E Berdel, Martin Dugas, Makoto Mark Taketo, Daneyal Farouq, Schraga Schwartz, Aviv Regev, Josée Hébert, Guy Sauvageau, Caroline Pabst, Stefan Hüttelmaier, Carsten Müller-Tidow
Leukaemogenesis requires enhanced self-renewal, which is induced by oncogenes. The underlying molecular mechanisms remain incompletely understood. Here, we identified C/D box snoRNAs and rRNA 2'-O-methylation as critical determinants of leukaemic stem cell activity. Leukaemogenesis by AML1-ETO required expression of the groucho-related amino-terminal enhancer of split (AES). AES functioned by inducing snoRNA/RNP formation via interaction with the RNA helicase DDX21. Similarly, global loss of C/D box snoRNAs with concomitant loss of rRNA 2'-O-methylation resulted in decreased leukaemia self-renewal potential...
June 26, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28646565/complete-molecular-remission-in-relapsed-and-refractory-acute-myeloid-leukaemia-with-mll-af9-treated-with-chidamide-based-chemotherapy
#5
Y Lun, J-J Yang, Y Wu
WHAT IS KNOWN AND OBJECTIVE: The mixed lineage leukaemia (MLL) gene translocations are found in approximately 10% of adults with acute myeloid leukaemia (AML) and are markers of poor prognosis. As the best reported response in relapsed and refractory MLL-rearranged AML is around 40%, reinduction treatment is very challenging for those patients. CASE DESCRIPTION: We report a case of relapsed and refractory AML with MLL-AF9, who did not respond to FLAG (fludarabine, cytarabine, granulocyte colony stimulating factor) regimen reinduction treatment, but achieved complete response and molecular remission after chidamide-based chemotherapy...
June 23, 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/28645776/selective-inhibition-of-flt3-by-gilteritinib-in-relapsed-or-refractory-acute-myeloid-leukaemia-a-multicentre-first-in-human-open-label-phase-1-2-study
#6
Alexander E Perl, Jessica K Altman, Jorge Cortes, Catherine Smith, Mark Litzow, Maria R Baer, David Claxton, Harry P Erba, Stan Gill, Stuart Goldberg, Joseph G Jurcic, Richard A Larson, Chaofeng Liu, Ellen Ritchie, Gary Schiller, Alexander I Spira, Stephen A Strickland, Raoul Tibes, Celalettin Ustun, Eunice S Wang, Robert Stuart, Christoph Röllig, Andreas Neubauer, Giovanni Martinelli, Erkut Bahceci, Mark Levis
BACKGROUND: Internal tandem duplication mutations in FLT3 are common in acute myeloid leukaemia and are associated with rapid relapse and short overall survival. The clinical benefit of FLT3 inhibitors in patients with acute myeloid leukaemia has been limited by rapid generation of resistance mutations, particularly in codon Asp835 (D835). We aimed to assess the highly selective oral FLT3 inhibitor gilteritinib in patients with relapsed or refractory acute myeloid leukaemia. METHODS: In this phase 1-2 trial, we enrolled patients aged 18 years or older with acute myeloid leukaemia who either were refractory to induction therapy or had relapsed after achieving remission with previous treatment...
June 20, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28644135/evaluation-of-thromboelastometry-parameters-as-predictive-markers-for-sinusoidal-obstruction-syndrome-in-patients-undergoing-allogeneic-stem-cell-transplantation-for-acute-leukaemia
#7
Joanna Rupa-Matysek, Lidia Gil, Ewelina Wojtasińska, Zuzanna Kanduła, Adam Nowicki, Magdalena Matuszak, Mieczysław Komarnicki
Hepatic sinusoidal obstruction syndrome (previously named veno-occlusive disease, SOS/VOD) is a serious complication of allogeneic stem cell transplantation (HSCT). Early identification of patients at risk of SOS/VOD may possibly improve the outcome and reduce mortality. Rotation thromboelastometry (ROTEM) is global assay allowing for the precise assessment of both bleeding and thrombotic conditions, however, its usefulness in patients undergoing HSCT for acute leukaemia has not been studied.We evaluated the thromboelastometry parameters in patients undergoing allogeneic HSCT for acute leukaemia to identify candidate biomarkers of SOS/VOD occurrence...
June 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28643375/dried-blood-spot-sampling-of-nilotinib-in-patients-with-chronic-myeloid-leukaemia-a-comparison-with-venous-blood-sampling
#8
Christel C L M Boons, Abdel Chahbouni, Anneliene M Schimmel, Abraham J Wilhelm, Yvonne M den Hartog, Jeroen J W M Janssen, N Harry Hendrikse, Jacqueline G Hugtenburg, Eleonora L Swart
OBJECTIVES: To compare nilotinib concentrations obtained by venous blood sampling and dried blood spot (DBS) in patients with chronic myeloid leukaemia (CML). It was investigated how to predict nilotinib plasma levels on the basis of DBS. METHODS: Forty duplicate DBS and venous blood samples were collected from 20 patients. Capillary blood was obtained by finger prick and spotted on DMPK-C Whatman sampling paper, simultaneously with venous blood sampling. Plasma concentrations were predicted from DBS concentrations using three methods: (1) individual and (2) mean haematocrit correction and (3) the bias between plasma and DBS concentrations...
June 23, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28642598/leukaemia-unravelling-the-heterogeneity-of-cancer-stem-cells
#9
Sarah Seton-Rogers
No abstract text is available yet for this article.
July 2017: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/28642591/donor-and-recipient-age-gender-and-abo-incompatibility-regardless-of-donor-source-validated-criteria-for-donor-selection-for-hematopoietic-transplants
#10
Y Wang, D-P Wu, Q-F Liu, L-P Xu, K-Y Liu, X-H Zhang, Y Xu, F Huang, X-J Huang
Prior data indicate similar outcomes after transplants from HLA-haplotype-matched relatives, HLA-identical siblings and HLA-matched unrelated donors. We used our prospective dataset to answer a clinically important question: who is the best donor for a person with acute leukemia transplanted in 1st complete remission. Patients were randomly divided into training (n=611) and validation (n=588) sets. 1199 consecutive subjects received a transplant from an HLA-haplotype-matched relative using granulocyte colony-stimulating factor (G-CSF) and anti-thymocyte globulin (ATG) (n=685) or an HLA-identical sibling (n=514); 3-year leukaemia-free survivals (LFSs) were 75 and 74% (P=0...
June 23, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28641618/-clinical-and-cytogenetic-characteristics-of-two-aml-patients-with-high-level-mll-expression
#11
Jia-Wei Zhao, Kun Ru, Cheng-Wen Li, Ke-Jing Tang, Ying-Chun Zheng, Cheng-Hua Cui, Jing Xiao, Sheng-Hua Chen, Xiao-Jing Wang
OBJECTIVE: To investigate the clinical and cytogenetic characteristics of high-level mixed-lineage leukaemia (MLL) gene amplification in patients with acute myeloid leukemia (AML). METHODS: The clinical and cytogenetic data of 2 AML patients with high-level MLL amplification from January 2010 to August 2016 were analyzed retrospectively. RESULTS: The two AML cases were in middle-aged population. They were diagnosed as FAB subtype M5b and M2a respectively...
June 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28641452/anti-inflammatory-and-antiproliferative-activities-of-ixora-brevifolia-benth-rubiaceae
#12
Rebeca P Medina, Vagner M de Moura, Cleuza C da Silva, Cecília M A de Oliveira, Lucilia Kato, Armando M Pomini, João E de Carvalho, Ana Lúcia T G Ruiz, Ciomar A Bersani-Amado, Silvana M O Santin
The crude extract and fractions from the branches of Ixora brevifolia, a tree found in the Brazilian Cerrado, were tested for anti-inflammatory and in vitro antiproliferative effects. The crude extract and n-hexane fraction exhibited significant inhibition of ear oedema in mice, while n-hexane-precipitated and chloroform fractions strongly inhibited the myeloperoxidase activity in ear tissue. The n-hexane and n-hexane-precipitated fractions showed strong growth inhibition for glioma cell line and the hydromethanolic fraction inhibited the growth of leukaemia cell line...
June 23, 2017: Natural Product Research
https://www.readbyqxmd.com/read/28639598/haematological-profile-of-patients-with-mixed-phenotype-acute-leukaemia-from-a-tertiary-care-centre-of-north-india
#13
Manupriya Sharma, Man Updesh Singh Sachdeva, Parveen Bose, Neelam Varma, Subhash Varma, R K Marwaha, Pankaj Malhotra
BACKGROUND & OBJECTIVES: Mixed-phenotype acute leukaemia (MPAL) is a rare neoplasm with no definite treatment protocols and a distinctly poor outcome. Advancement in polychromatic flow cytometry has made its identification easier. This prospective study was designed to identify cases of MPAL and study their clinical presentation and haematological profile in a tertiary care hospital in north India. METHODS: Ethylenediaminetetraacetic acid (EDTA)-anticoagulated bone marrow aspirate samples of patients diagnosed as acute leukaemia (AL) on the basis of morphology were utilized for immunophenotyping...
February 2017: Indian Journal of Medical Research
https://www.readbyqxmd.com/read/28637487/the-nf1-somatic-mutational-landscape-in-sporadic-human-cancers
#14
REVIEW
Charlotte Philpott, Hannah Tovell, Ian M Frayling, David N Cooper, Meena Upadhyaya
BACKGROUND: Neurofibromatosis type 1 (NF1: Online Mendelian Inheritance in Man (OMIM) #162200) is an autosomal dominantly inherited tumour predisposition syndrome. Heritable constitutional mutations in the NF1 gene result in dysregulation of the RAS/MAPK pathway and are causative of NF1. The major known function of the NF1 gene product neurofibromin is to downregulate RAS. NF1 exhibits variable clinical expression and is characterized by benign cutaneous lesions including neurofibromas and café-au-lait macules, as well as a predisposition to various types of malignancy, such as breast cancer and leukaemia...
June 21, 2017: Human Genomics
https://www.readbyqxmd.com/read/28636094/characterization-of-clonal-philadelphia-negative-cytogenetic-abnormalities-in-a-large-cohort-of-chronic-myeloid-leukemia
#15
Xiangjun Chen, Jine Zheng, Kaiwei Liang, Yanli He, Wen Du, Juan Li, Wei Liu, Yanjie Hu, Junxia Yao
OBJECTIVES: Clonal Philadelphia-negative Cytogenetic Abnormalities (CPCA) have been reported in chronic myeloid leukaemia (CML) patients treated with either interferon or tyrosine kinase inhibitor (TKI). However, the incidences and types of these cytogenetic abnormalities after treatment vary due to the limited populations enrolled. METHODS: We analysed the frequency and types of CPCA in a cohort of 607 CML patients in the chronic phase after TKI treatment. We also followed up these CPCA with a median of 31...
June 21, 2017: Internal Medicine Journal
https://www.readbyqxmd.com/read/28631944/clinical-significance-of-repeat-blood-cultures-during-febrile-neutropenia-in-adult-acute-myeloid-leukaemia-patients-undergoing-intensive-chemotherapy
#16
Shun-Ichi Kimura, Ayumi Gomyo, Jin Hayakawa, Masaharu Tamaki, Yu Akahoshi, Naonori Harada, Tomotaka Ugai, Machiko Kusuda, Kazuaki Kameda, Hidenori Wada, Yuko Ishihara, Koji Kawamura, Kana Sakamoto, Miki Sato, Kiriko Terasako-Saito, Misato Kikuchi, Hideki Nakasone, Shinichi Kako, Aki Tanihara, Yoshinobu Kanda
BACKGROUND: We evaluated the clinical significance of repeat blood cultures in persistent and recurrent fever during neutropenia in adult acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) patients undergoing intensive chemotherapy. METHODS: We retrospectively reviewed the chemotherapy cycles at our centre between January 2007 and December 2015. Blood cultures obtained within three days after initial febrile neutropenia (FN) were defined as initial blood cultures and those obtained on or after day 4 were defined as repeat blood cultures...
June 20, 2017: Infectious Diseases
https://www.readbyqxmd.com/read/28631441/genetic-landscape-and-deregulated-pathways-in-b-cell-lymphoid-malignancies
#17
R Rosenquist, S Beà, M-Q Du, B Nadel, Q Pan-Hammarström
With the introduction of next-generation sequencing, the genetic landscape of the complex group of B-cell lymphoid malignancies has rapidly been unravelled in recent years. This has provided important information about recurrent genetic events and identified key pathways deregulated in each lymphoma subtype. In parallel, there has been intense search and development of novel types of targeted therapy that 'hit' central mechanisms in lymphoma pathobiology, such as BTK, PI3K or BCL2 inhibitors. In this review, we will outline the current view of the genetic landscape of selected entities: follicular lymphoma, diffuse large B-cell lymphoma, mantle cell lymphoma, chronic lymphocytic leukaemia and marginal zone lymphoma...
June 20, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28631179/population-pharmacokinetics-of-volasertib-administered-in-patients-with-acute-myeloid-leukaemia-as-a-single-agent-or-in-combination-with-cytarabine
#18
Belén P Solans, Angèle Fleury, Matthias Freiwald, Holger Fritsch, Karin Haug, Iñaki F Trocóniz
BACKGROUND: Volasertib, a potent and selective polo-like kinase inhibitor, has shown to increase response rates and improve survival with a clinically manageable safety profile, administered alone and in combination with cytarabine in patients with acute myeloid leukaemia. OBJECTIVES: The objectives of this analysis were to describe the pharmacokinetics of volasertib and cytarabine, administered as single agents or in combination. METHODS: Three thousand, six hundred and six plasma volasertib concentrations from 501 patients receiving either volasertib alone, or in combination with cytarabine, and 826 plasma cytarabine concentrations from 650 patients receiving cytarabine as multiple subcutaneous injections per cycle either alone, or in combination with volasertib, were analysed using NONMEM Version 7...
June 19, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28628276/acute-myeloid-leukaemia-relapsing-after-allogeneic-haematopoietic-stem-cell-transplantation-prognostic-factors-and-impact-of-initial-therapy-of-relapse
#19
Andrew B M Lim, Cameron Curley, Chun Yew Fong, Ian Bilmon, Ashanka Beligaswatte, Duncan Purtill, Bartlomiej Getta, Anne Maree Johnston, Tasman Armytage, Marnie Collins, Kate Mason, Katherine Fielding, Matthew Greenwood, John Gibson, Mark Hertzberg, Matthew Wright, Ian Lewis, John Moore, David Curtis, Jeff Szer, Glen Kennedy, David Ritchie
AIMS: We sought to determine factors associated with overall survival from relapse (OSR) of acute myeloid leukaemia (AML) after allogeneic haematopoietic stem cell transplantation (alloHSCT), and the effect of first salvage therapy and subsequent GVHD on OSR. METHODS: Data on 386 patients from nine Australian centres with relapsed AML post-alloHSCT were collected retrospectively. OSR was calculated using the Kaplan-Meier method. Univariate and multivariate analyses were conducted using the logrank test and proportional hazards modelling respectively, and a prognostic index for OSR was derived from multivariate modelling...
June 19, 2017: Internal Medicine Journal
https://www.readbyqxmd.com/read/28628088/an-individualised-risk-adapted-protocol-of-pre-and-post-transplant-zoledronic-acid-reduces-bone-loss-after-allogeneic-stem-cell-transplantation-results-of-a-phase-ii-prospective-trial
#20
A Grigg, B Butcher, B Khodr, A Bajel, M Hertzberg, S Patil, A B D'Souza, P Ganly, P Ebeling, E Wong
Bone loss occurs frequently following allogeneic haematopoietic stem cell transplantation (alloSCT). The Australasian Leukaemia and Lymphoma Group conducted a prospective phase II study of pretransplant zoledronic acid (ZA) and individualised post-transplant ZA to prevent bone loss in alloSCT recipients. Patients received ZA 4 mg before conditioning. Administration of post-transplant ZA from days 100 to 365 post alloSCT was determined by a risk-adapted algorithm based on serial bone density assessments and glucocorticoid exposure...
June 19, 2017: Bone Marrow Transplantation
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