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https://www.readbyqxmd.com/read/28548938/nkp30-expression-is-a-prognostic-immune-biomarker-for-stratification-of-patients-with-intermediate-risk-acute-myeloid-leukemia
#1
Anne-Sophie Chretien, Cyril Fauriat, Florence Orlanducci, Jerome Rey, Gaelle Bouvier Borg, Emmanuel Gautherot, Samuel Granjeaud, Clemence Demerle, Jean-François Hamel, Adelheid Cerwenka, Elke Pogge von Strandmann, Norbert Ifrah, Catherine Lacombe, Pascale Cornillet-Lefebvre, Jacques Delaunay, Antoine Toubert, Christine Arnoulet, Norbert Vey, Daniel Olive
Cytogenetics and European Leukemia Net (ELN) genetic classification predict patients at increased risk of relapse in acute myeloid leukemia (AML) except in the intermediate risk group for which further prognostic determinants are required. We have previously shown that Natural Killer (NK) cell defects in AML are predictors of poor overall survival (OS). This study aimins at validating NKp30, a receptor that mediates NK activation, as a prognostic biomarker for AML patients with intermediate prognosis.NKp30 expression was prospectively assessed at diagnosis on NK cells from peripheral blood by flow cytometry (N = 201 patients)...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28548643/condensed-versus-standard-schedule-of-high-dose-cytarabine-consolidation-therapy-with-pegfilgrastim-growth-factor-support-in-acute-myeloid-leukemia
#2
S Jaramillo, A Benner, J Krauter, H Martin, T Kindler, M Bentz, H R Salih, G Held, C-H Köhne, K Götze, M Lübbert, A Kündgen, P Brossart, M Wattad, H Salwender, B Hertenstein, D Nachbaur, G Wulf, H-A Horst, H Kirchen, W Fiedler, A Raghavachar, G Russ, S Kremers, E Koller, V Runde, G Heil, D Weber, G Göhring, K Döhner, A Ganser, H Döhner, R F Schlenk
The aim of this cohort study was to compare a condensed schedule of consolidation therapy with high-dose cytarabine on days 1, 2 and 3 (HDAC-123) with the HDAC schedule given on days 1, 3 and 5 (HDAC-135) as well as to evaluate the prophylactic use of pegfilgrastim after chemotherapy in younger patients with acute myeloid leukemia in first complete remission. One hundred and seventy-six patients were treated with HDAC-135 and 392 patients with HDAC-123 with prophylactic pegfilgrastim at days 10 and 8, respectively, in the AMLSG 07-04 and the German AML Intergroup protocol...
May 26, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28548080/discovery-of-first-in-class-reversible-dual-small-molecule-inhibitors-against-g9a-and-dnmts-in-hematological-malignancies
#3
Edurne San José-Enériz, Xabier Agirre, Obdulia Rabal, Amaia Vilas-Zornoza, Juan A Sanchez-Arias, Estibaliz Miranda, Ana Ugarte, Sergio Roa, Bruno Paiva, Ander Estella-Hermoso de Mendoza, Rosa María Alvarez, Noelia Casares, Victor Segura, José I Martín-Subero, François-Xavier Ogi, Pierre Soule, Clara M Santiveri, Ramón Campos-Olivas, Giancarlo Castellano, Maite Garcia Fernandez de Barrena, Juan Roberto Rodriguez-Madoz, Maria José García-Barchino, Juan Jose Lasarte, Matias A Avila, Jose Angel Martinez-Climent, Julen Oyarzabal, Felipe Prosper
The indisputable role of epigenetics in cancer and the fact that epigenetic alterations can be reversed have favoured development of epigenetic drugs. In this study, we design and synthesize potent novel, selective and reversible chemical probes that simultaneously inhibit the G9a and DNMTs methyltransferase activity. In vitro treatment of haematological neoplasia (acute myeloid leukaemia-AML, acute lymphoblastic leukaemia-ALL and diffuse large B-cell lymphoma-DLBCL) with the lead compound CM-272, inhibits cell proliferation and promotes apoptosis, inducing interferon-stimulated genes and immunogenic cell death...
May 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/28547571/clinical-presentations-and-molecular-studies-of-invasive-renal-epithelioid-angiomyolipoma
#4
Cheng-Keng Chuang, Hsin Chia Angela Lin, Han-Yu Tasi, Kun-Han Lee, Yuting Kao, Fukai Leo Chuang, Ying-Hsu Chang, Po-Hung Lin, Chung-Yi Liu, See-Tong Pang
PURPOSE: Epithelioid angiomyolipoma (EAML) is a rare variant of renal angiomyolipoma with malignant potential, and the cytogenetic and clinical behavior of EAML remains a challenging issue. METHODS: We retrospectively analyze the clinical courses of five EAML, the use of everolimus on metastatic EAML, and next-generation sequencing (NGS) and polymerase chain reaction (PCR) studies to investigate the gene mutation of TSC and the impact of PI3K/Akt/mTOR signaling pathway in metastatic EAML...
May 25, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28547134/clinical-radiographic-and-biochemical-characteristics-of-adult-hypophosphatasia
#5
T Schmidt, H Mussawy, T Rolvien, T Hawellek, J Hubert, W Rüther, M Amling, F Barvencik
In this study, we report on clinical, radiographic and biochemical characteristics of 38 patients with adult hypophosphatasia. High-resolution peripheral quantitative computed tomography showed alterations of bone microstructure in a subgroup of 14 patients. Pyridoxal-5-phosphate levels correlated with the occurrence of fractures and the number of symptoms. INTRODUCTION: Hypophosphatasia (HPP) is a rare disorder with a wide range of clinical manifestations. A reduced enzymatic activity of alkaline phosphatase (ALP) is the key marker of the disease, causing an accumulation of ALP substrates such as pyridoxal-5-phosphate (PLP)...
May 25, 2017: Osteoporosis International
https://www.readbyqxmd.com/read/28546581/a-phase-1b-2b-multicenter-study-of-oral-panobinostat-plus-azacitidine-in-adults-with-mds-cmml-or-aml-with-%C3%A2-30-blasts
#6
G Garcia-Manero, M A Sekeres, M Egyed, M Breccia, C Graux, J D Cavenagh, H Salman, A Illes, P Fenaux, D J DeAngelo, R Stauder, K Yee, N Zhu, J-H Lee, D Valcarcel, A MacWhannell, Z Borbenyi, L Gazi, S Acharyya, S Ide, M Marker, O G Ottmann
Treatment with azacitidine (AZA), a demethylating agent, prolonged overall survival (OS) vs conventional care in patients with higher-risk myelodysplastic syndromes (MDS). As median survival with monotherapy is <2 years, novel agents are needed to improve outcomes. This phase 1b/2b trial (n=113) was designed to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of panobinostat (PAN) + AZA (phase 1b) and evaluate early efficacy and safety of PAN+AZA vs AZA monotherapy (phase 2b) in patients with higher-risk MDS, chronic myelomonocytic leukemia, or oligoblastic acute myeloid leukemia with <30% blasts...
May 26, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28546144/midostaurin-approved-for-flt3-mutated-aml
#7
Mark Levis
Midostaurin was recently approved by the U.S. Food and Drug Administration for the treatment of FLT3-mutant acute myeloid leukemia (AML). This is the first drug to receive regulatory approval for AML in the U.S. since the year 2000. Midostaurin is a small molecule kinase inhibitor with activity against the receptor tyrosine kinase FLT3, and its approval will hopefully mark the beginning of an era of targeted agents for the treatment of molecularly-defined subtypes of AML.
May 25, 2017: Blood
https://www.readbyqxmd.com/read/28545196/comparison-of-cox-regression-and-parametric-models-application-for-assessment-of-survival-of-pediatric-cases-of-acute-leukemia-in-southern-iran
#8
Saeed Hosseini Teshnizi, Seyyed Mohammad Taghi Ayatollahi
Background: Finding the most appropriate regression model for survival data in cancer casesin order to determine prognosis is an important issue in medical research. Here we compare Cox and parametric regression models regarding survival of children with acute leukemia in southern Iran. Methods: In a retrospective cohort study, information for 197 children with acute leukemia over 6 years was collected through observation and interviews. In order to identify factors affecting their survival, the Cox and parametric (exponential, Weibull, log-logistic, log-normal, Gompertz and generalized gamma) models were fitted to the data...
April 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28543682/residual-thymic-tissue-and-lymph-node-involvement-by-acute-myeloid-leukaemia-presenting-as-mediastinal-strongly-18-fdg-pet-positive-masses
#9
Georg Maschmeyer, Ingo Brink, Doris Jähne, Renate Arnold, Olaf Schega
We report on a multidisciplinary management of a 68-year old AML patient presenting with a PET-positive mediastinal tumour typical for lymph node metastasis. It was removed via minimally invasive thoracoscopic intervention and was identified as a thymus residual infiltrated by AML. Follow-up PET-CT scan after resection and remission induction chemotherapy was completely normal. To our knowledge, this is the first documented case report of AML presenting with PET-positive infiltrates of thymic and lymph node tissue along the aortic bow mimicking a second intrathoracic malignancy...
May 22, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28542862/subsequent-primary-malignancies-after-diffuse-large-b-cell-lymphoma-in-the-modern-treatment-era
#10
Li Tao, Christina A Clarke, Aaron S Rosenberg, Ranjana H Advani, Brian A Jonas, Christopher R Flowers, Theresa H M Keegan
With the addition of rituximab and other treatment advances, survival after diffuse large B-cell lymphoma (DLBCL) has improved, but subsequent primary malignancies (SPMs) have emerged as an important challenge for DLBCL survivorship. We calculated standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for SPMs among 23 879 patients who survived at least 1 year after a first primary DLBCL diagnosed during 1989-2012, compared to the general population in California. Cumulative incidence (CMI) of SPMs, accounting for the competing risk of death, also was calculated...
May 25, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28542715/hyperleucocytosis-in-paediatric-acute-myeloid-leukaemia-the-challenge-of-white-blood-cell-counts-above-200%C3%A2-%C3%A3-%C3%A2-10-9-l-the-nopho-experience-1984-2014
#11
Bernward Zeller, Heidi Glosli, Erik Forestier, Shau-Yin Ha, Kirsi Jahnukainen, Ólafur G Jónsson, Birgitte Lausen, Josefine Palle, Henrik Hasle, Jonas Abrahamsson
Hyperleucocytosis in paediatric acute myeloid leukaemia (AML) is associated with increased morbidity and mortality. We studied hyperleucocytosis in 890 patients with AML aged 0-18 years registered in the Nordic Society of Paediatric Haematology and Oncology (NOPHO) registry, with special focus on very high white blood cell counts (WBC >200 × 10/l). Eighty-six patients (10%) had WBC 100-199 × 10(9) /l and 57 (6%) had WBC ≥200 × 10(9) /l. Patients with WBC ≥200 × 10(9) /l had a high frequency of t(9;11) and a paucity of trisomy 8...
May 25, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28541716/investigational-bet-bromodomain-protein-inhibitors-in-early-stage-clinical-trials-for-acute-myelogenous-leukemia-aml
#12
Thorsten Braun, Claude Gardin
Acute myelogenous leukemia (AML) is a heterogeneous group of malignancies driven by genetic mutations and deregulated epigenetic control. Relapse/refractory disease remains frequent in younger patients and even more so in older patients, including treatment with epigenetic drugs in this age group, mainly with hypomethylating agents. New treatment strategies are urgently needed. The recent discovery that epigenetic readers of the bromodomain (BRD) and extraterminal (BET) protein family, are crucial for AML maintenance by transcription of oncogenic c-MYC lead to rapid development of BET inhibitors entering clinical trials...
May 25, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28541603/comparison-of-first-line-chemotherapy-including-escalated-beacopp-versus-chemotherapy-including-abvd-for-people-with-early-unfavourable-or-advanced-stage-hodgkin-lymphoma
#13
REVIEW
Nicole Skoetz, Andrea Will, Ina Monsef, Corinne Brillant, Andreas Engert, Bastian von Tresckow
BACKGROUND: There are two different international standards for the treatment of early unfavourable and advanced stage Hodgkin lymphoma (HL): chemotherapy with escalated BEACOPP (bleomycin/etoposide/doxorubicin/cyclophosphamide/vincristine/procarbazine/prednisone) regimen and chemotherapy with ABVD (doxorubicin/bleomycin/vinblastine/dacarbazine) regimen. OBJECTIVES: To determine the advantages and disadvantages of chemotherapy including escalated BEACOPP compared to chemotherapy including ABVD in the treatment of early unfavourable or advanced stage HL as first-line treatment...
May 25, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28540755/persistent-cytogenetic-abnormalities-in-patients-undergoing-intensive-chemotherapy-for-acute-myeloid-leukemia
#14
Lalit Saini, Joseph Brandwein, Artur Szkotak, Sunita Ghosh, Irwindeep Sandhu
We evaluated the impact of bone marrow sample characteristics on the detection of persistent cytogenetic abnormalities (PCA) following induction chemotherapy for acute myeloid leukemia (AML). PCA's were identified in 20.4% of patients and were more common with complete remission without count recovery (CRi) vs. those with count recovery (CR, 45.8 vs. 13.5%, p = .001), with  >2% blasts vs.  ≤2% blasts (42 vs. 12%, p =  .001) and with hypocellular trephine biopsies relative to those with normo/hypercellular biopsies (42...
May 25, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28540746/kdm3b-shows-tumor-suppressive-activity-and-transcriptionally-regulates-hoxa1-through-retinoic-acid-response-elements-in-acute-myeloid-leukemia
#15
Xin Xu, Stefan Nagel, Hilmar Quentmeier, Zhanju Wang, Claudia Pommerenke, Wilhelm G Dirks, Roderick A F Macleod, Hans G Drexler, Zhenbo Hu
KDM3B reportedly shows both tumor-suppressive and tumor-promoting activities in leukemia. The function of KDM3B is likely cell-type dependent and its seeming functional discordance may reflect its phenotypic dependence on downstream targets. Here, we first showed the underexpression of KDM3B in acute myeloid leukemia (AML) patients and AML cell lines with MLL-AF6/9 or PML-RARA translocations. Overexpression of KDM3B repressed colony formation of AML cell line with 5q deletion. We then performed global microarray profiling to identify potential downstream targets of KDM3B, notably HOXA1, which was verified by real time PCR and Western blotting...
May 25, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28539478/a-novel-epigenetic-aml1-eto-thap10-mir-383-mini-circuitry-contributes-to-t-8-21-leukaemogenesis
#16
Yonghui Li, Qiaoyang Ning, Jinlong Shi, Yang Chen, Mengmeng Jiang, Li Gao, Wenrong Huang, Yu Jing, Sai Huang, Anqi Liu, Zhirui Hu, Daihong Liu, Lili Wang, Clara Nervi, Yun Dai, Michael Q Zhang, Li Yu
DNA methylation patterns are frequently deregulated in t(8;21) acute myeloid leukaemia (AML), but little is known of the mechanisms by which specific gene sets become aberrantly methylated. Here, we found that the promoter DNA methylation signature of t(8;21)(+) AML blasts differs from that of t(8;21)(-) AMLs. This study demonstrated that a novel hypermethylated zinc finger-containing protein, THAP10, is a target gene and can be epigenetically suppressed by AML1-ETO at the transcriptional level in t(8;21) AML...
May 24, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28538707/self-esteem-and-academic-difficulties-in-preadolescents-and-adolescents-healed-from-paediatric-leukaemia
#17
Marta Tremolada, Livia Taverna, Sabrina Bonichini, Giuseppe Basso, Marta Pillon
Adolescents with cancer may demonstrate problems in their self-esteem and schooling. This study aims to screen the preadolescents and adolescents more at risk in their self-esteem perception and schooling difficulties post-five years from the end of therapy. Twenty-five paediatric ex-patients healed from leukaemia were recruited at the Haematology-Oncologic Clinic (University of Padua). The mean age of the children was 13.64 years (Standard Deviation (SD)) = 3.08, range = 10-19 years), most were treated for acute lymphoblastic leukaemia (ALL) (84%) and relatively equally distributed by gender...
May 24, 2017: Cancers
https://www.readbyqxmd.com/read/28538663/the-cytokine-flt3-ligand-in-normal-and-malignant-hematopoiesis
#18
REVIEW
Panagiotis Tsapogas, Ciaran James Mooney, Geoffrey Brown, Antonius Rolink
The cytokine Fms-like tyrosine kinase 3 ligand (FL) is an important regulator of hematopoiesis. Its receptor, Flt3, is expressed on myeloid, lymphoid and dendritic cell progenitors and is considered an important growth and differentiation factor for several hematopoietic lineages. Activating mutations of Flt3 are frequently found in acute myeloid leukemia (AML) patients and associated with a poor clinical prognosis. In the present review we provide an overview of our current knowledge on the role of FL in the generation of blood cell lineages...
May 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28538183/runx1-eto-and-runx1-evi1-differentially-reprogram-the-chromatin-landscape-in-t-8-21-and-t-3-21-aml
#19
Justin Loke, Salam A Assi, Maria Rosaria Imperato, Anetta Ptasinska, Pierre Cauchy, Yura Grabovska, Natalia Martinez Soria, Manoj Raghavan, H Ruud Delwel, Peter N Cockerill, Olaf Heidenreich, Constanze Bonifer
Acute myeloid leukemia (AML) is a heterogeneous disease caused by mutations in transcriptional regulator genes, but how different mutant regulators shape the chromatin landscape is unclear. Here, we compared the transcriptional networks of two types of AML with chromosomal translocations of the RUNX1 locus that fuse the RUNX1 DNA-binding domain to different regulators, the t(8;21) expressing RUNX1-ETO and the t(3;21) expressing RUNX1-EVI1. Despite containing the same DNA-binding domain, the two fusion proteins display distinct binding patterns, show differences in gene expression and chromatin landscape, and are dependent on different transcription factors...
May 23, 2017: Cell Reports
https://www.readbyqxmd.com/read/28537804/evaluation-of-testing-of-acute-leukemia-samples-survey-result-from-the-college-of-american-pathologists
#20
Tracy I George, Joseph A Tworek, Nicole E Thomas, Lisa A Fatheree, Rhona J Souers, Raouf E Nakhleh, Daniel A Arber
CONTEXT: - The classification and prognosis determination in acute leukemia (AL) are complex and it is unclear what testing is being performed in practice. OBJECTIVE: - To survey physicians describing their current practice of test ordering in the diagnosis of AL. DESIGN: - In anticipation of a guideline by the College of American Pathologists (CAP) and the American Society for Hematology on laboratory testing needed for the initial workup of AL, a baseline survey was designed by an expert panel from CAP...
May 24, 2017: Archives of Pathology & Laboratory Medicine
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