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https://www.readbyqxmd.com/read/29334312/targeting-of-phospho-eif4e-by-homoharringtonine-eradicates-a-distinct-subset-of-human-acute-myeloid-leukemia
#1
Hong Zhou, Rong Zhen Xu, Ying Gu, Peng Fei Shi, Shenxian Qian
More than half of the patients with acute myeloid leukemia (AML) fail to achieve long-term disease-free survival with current therapies and novel therapeutic strategies are urgently needed. The effects of homoharringtonine (HHT) on the growth of AML cell lines and primary leukemia cells were examined using MTT, colony formation assay. The effects of HHT on both eukaryotic translation initiation factor 4E (eIF4E) and phospho-eIF4E(p-eIF4E) were examined through western blot and immunofluorescence staining. HHT selectively reduced levels of p-eIF4E and its downstream oncoprotein Mcl-1, and potently inhibited in vitro and in vivo the growth of a distinct subset of AML cells and primary leukemia cells expressing high level of p-eIF4E through apoptosis...
January 15, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29333579/factors-associated-with-the-number-and-size-of-renal-angiomyolipomas-in-sporadic-angiomyolipoma-saml-a-study-of-adult-patients-with-saml-managed-in-a-dutch-tertiary-referral-center
#2
J L H Ruud Bosch, Francis Vekeman, Mei Sheng Duh, Maureen Neary, Matthew Magestro, Jonathan Fortier, Paul Karner, Raluca Ionescu-Ittu, Bernard A Zonnenberg
PURPOSE: To describe the patient characteristics, treatments, disease monitoring, and kidney function of patients with sporadic angiomyolipoma (sAML), stratified by the number and size of renal angiomyolipomas (AMLs). METHODS: Single-center retrospective analysis of patients with sAML treated from 1990 to 2015 in a dedicated clinic for inheritable tumor syndromes in a tertiary referral center from the Netherlands. Patients' first AML assessment at the clinic was defined as the index date...
January 15, 2018: International Urology and Nephrology
https://www.readbyqxmd.com/read/29332925/pulmonary-artery-pseudoaneurysm-secondary-to-lung-inf-lammation
#3
Shinichirou Ishimoto, Hiroyuki Sakurai, Ryouta Higure, Riken Kawachi, Mie Shimamura
Pulmonary artery aneurysms (PAA) and pseudoaneurysms (PAP) are caused by infections, vasculitis, trauma, pulmonary hypertension, congenital heart disease, and connective tissue disease. Most cases of such aneurysm occur in the trunk or major branches of the pulmonary artery, while the peripheral type is less common. The treatment modalities are medical therapy, surgery, and percutaneous catheter embolization. The mortality rate associated with rupture is approximately 50%. We encountered a case of a 53-year-old man with a pulmonary artery pseudoaneurysm secondary to pneumonia and cavity formation during chemotherapy for acute myeloid leukemia (AML)...
January 15, 2018: Annals of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/29332326/carcinogenic-potential-of-antitumor-therapies-is-the-risk-predictable
#4
Ivanka Nenova, Janet Grudeva-Popova
The growing number of successfully cured cancer patients has created a new field in oncogenesis. The life expectancy of such patients has increased, however this favorable event may create enough time for epigenetic events to occur which can cause a new carcinognic event, i.e. a secondary malignancy. The terms in use are second primary malignancies as well as therapy-related neoplasms in case the treatment of the first neoplasm is a direct cause. Second primary malignancies can be hematological neoplasms or solid tumors, with solid tumors having higher frequency...
November 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29331774/the-synergy-of-vitamin-c-with-decitabine-activates-tet2-in-leukemic-cells-and-significantly-improves-overall-survival-in-elderly-patients-with-acute-myeloid-leukemia
#5
Huihui Zhao, Huayuan Zhu, Jiayu Huang, Yu Zhu, Ming Hong, Han Zhu, Jingjing Zhang, Shan Li, Lijia Yang, Yun Lian, Shuai Wang, Jianping Mao, Yaoyu Chen, Jianyong Li, Sixuan Qian
BACKGROUND: Decitabine is widely used in the treatment of acute myeloid leukemia (AML) in elderly patients. Low-dose Vitamin C has also been indicated to induce DNA demethylation at the cellular level. However, little is known whether low-dose Vitamin C has a synergistic effect with decitabine in clinic. METHODS: The effect of combined low-dose Vitamin C and decitabine on cell proliferation, the cell cycle, apoptosis and the expression level and activity of TET2 was investigated in HL60 and NB4 human leukemic cells...
January 2, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29330746/risk-stratified-therapy-for-children-with-flt3-itd-positive-acute-myeloid-leukemia-results-from-the-jplsg-aml-05-study
#6
Akira Shimada, Yuka Iijima-Yamashita, Akio Tawa, Daisuke Tomizawa, Miho Yamada, Shiba Norio, Tomoyuki Watanabe, Takashi Taga, Shotaro Iwamoto, Kiminori Terui, Hiroshi Moritake, Akitoshi Kinoshita, Hiroyuki Takahashi, Hideki Nakayama, Katsuyoshi Koh, Hiroaki Goto, Yoshiyuki Kosaka, Akiko Moriya Saito, Nobutaka Kiyokawa, Keizo Horibe, Yusuke Hara, Kentaro Oki, Yasuhide Hayashi, Shiro Tanaka, Souichi Adachi
Acute myeloid leukemia harboring internal tandem duplication of FMS-like tyrosine kinase 3 (AMLFLT3-ITD) is associated with poor prognosis. We evaluated the results of the AML-05 study, in which all AMLFLT3-ITD patients were assigned to receive hematopoietic stem cell transplantation (HSCT) in the first remission (1CR). We also investigated the effects of additional genetic alterations on FLT3-ITD. The 5-year overall survival (OS) and event-free survival (EFS) rates among the 47 AMLFLT3-ITD patients were 42...
January 12, 2018: International Journal of Hematology
https://www.readbyqxmd.com/read/29330221/minimal-measurable-residual-disease-in-aml-consensus-document-from-eln-mrd-working-party
#7
Gerrit J Schuurhuis, Michael Heuser, Sylvie Freeman, Marie-Christine Béné, Francesco Buccisano, Jacqueline Cloos, David Grimwade, Torsten Haferlach, Robert K Hills, Christopher S Hourigan, Jeffrey L Jorgensen, Wolfgang Kern, Francis Lacombe, Luca Maurillo, Claude Preudhomme, Bert A van der Reijden, Christian Thiede, Adriano Venditti, Paresh Vyas, Brent L Wood, Roland B Walter, Konstanze Döhner, Gail J Roboz, Gert J Ossenkoppele
Measurable residual disease (MRD, previously termed minimal residual disease) is an independent, post-diagnosis, prognostic indicator in acute myeloid leukemia (AML) that is important for risk stratification and treatment planning, in conjunction with other well-established clinical, cytogenetic, and molecular data assessed at diagnosis. MRD can be evaluated using a variety of multi-parameter flow cytometry (MFC) and molecular protocols but, to date, these approaches have not been qualitatively or quantitatively standardized, making their use in clinical practice challenging...
January 12, 2018: Blood
https://www.readbyqxmd.com/read/29330206/evolution-of-cytogenetically-normal-acute-myeloid-leukemia-during-therapy-and-relapse-an-exome-sequencing-study-of-50-patients
#8
Philipp A Greif, Luise Hartmann, Sebastian Vosberg, Sophie Stief, Raphael Mattes, Ines Hellmann, Klaus H Metzeler, Tobias Herold, Stefanos Bamopoulos, Paul Kerbs, Vindi Jurinovic, Daniela Schumacher, Friederike Pastore, Kathrin Bräundl, Evelyn Zellmeier, Bianka Ksienzyk, Nikola Konstandin, Stephanie Schneider, Alexander Graf, Stefan Krebs, Helmut Blum, Martin Neumann, Claudia Baldus, Stefan K Bohlander, Stephan Wolf, Dennis Goerlich, Wolfgang E Berdel, Bernhard J Woermann, Wolfgang Hiddemann, Karsten Spiekermann
PURPOSE: To study mechanisms of therapy-resistance and disease progression, we analyzed the evolution of cytogenetically normal acute myeloid leukemia (CN-AML) based on somatic alterations. EXPERIMENTAL DESIGN: We performed exome-sequencing of matched diagnosis, remission and relapse samples from 50 CN-AML patients treated with intensive chemotherapy. Mutation patterns were correlated with clinical parameters. RESULTS: Evolutionary patterns correlated with clinical outcome...
January 12, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29328966/cementum-as-a-source-of-dna-in-challenging-forensic-cases
#9
Hussam Mansour, Oliver Krebs, Jan Peter Sperhake, Christa Augustin, Till Koehne, Michael Amling, Klaus Püschel
Each forensic case is characterized by its own uniqueness. Deficient forensic cases require additional sources of human identifiers to assure the identity. We report on two different cases illustrating the role of teeth in answering challenging forensic questions. The first case involves identification of an adipocere male found in a car submersed in water for approximately 2 years. The second scenario, which involves paternity DNA testing of an exhumed body, was performed approximately 2.8 years post-mortem...
January 3, 2018: Journal of Forensic and Legal Medicine
https://www.readbyqxmd.com/read/29327940/the-different-faces-of-renal-angiomyolipomas-on-radiologic-imaging-a-pictorial-review
#10
Shanigarn Thiravit, Wanwarang Teerasamit, Phakphoom Thiravit
Renal angiomyolipoma (AML) is an uncommon renal tumour, generally composed of mature adipose tissue, dysmorphic blood vessels, and smooth muscle. Identification of intratumoural fat on unenhanced CT images (UECT) is the most reliable finding for establishing the diagnosis of renal AML. However, AMLs sometimes exhibit atypical findings, including cystic as well as solid forms; some of these variants overlap with the appearance of other renal tumours. A rare type of AML, the epithelioid type, possesses malignant potential...
January 12, 2018: British Journal of Radiology
https://www.readbyqxmd.com/read/29327808/the-rocky-road-to-personalized-medicine-in-acute-myeloid-leukaemia
#11
REVIEW
Bryan Brinda, Irum Khan, Brian Parkin, Heiko Konig
Acute myeloid leukaemia (AML) is a malignant disorder of the myeloid blood lineage characterized by impaired differentiation and increased proliferation of hematopoietic precursor cells. Recent technological advances have led to an improved understanding of AML biology but also uncovered the enormous cytogenetic and molecular heterogeneity of the disease. Despite this heterogeneity, AML is mostly managed by a 'one-size-fits-all' approach consisting of intensive, highly toxic induction and consolidation chemotherapy...
January 12, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29326802/allogeneic-hematopoietic-stem-cell-transplantation-in-therapy-related-myeloid-neoplasms-t-mn-of-the-adult-monocentric-observational-study-and-review-of-the-literature
#12
Elisabetta Metafuni, Patrizia Chiusolo, Luca Laurenti, Federica Sorà, Sabrina Giammarco, Andrea Bacigalupo, Giuseppe Leone, Simona Sica
Background: Therapy related myeloid neoplasms (t-MN) occur due to direct mutational events of chemotherapeutic agents and radiotherapy. Disease latency, mutational events and prognosis vary with drugs categories. Methods: We describe a cohort of 30 patients, 18 females and 12 males, with median age of 52.5 years (range, 20 to 64), submitted to allogeneic stem cell transplantation (HSCT) in our department between September 1999 and March 2017. Patients had a history of solid tumour in 14 cases, haematological disease in 15 cases and both of them in one case...
2018: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/29324476/revisiting-autologous-transplantation-in-acute-myeloid-leukemia
#13
Chezi Ganzel, Jacob M Rowe
PURPOSE OF REVIEW: Autologous hematopoietic cell transplantation (auto-HCT) has been evaluated as a consolidation treatment for acute myeloid leukemia (AML) in the 1980s and 1990s. These prospective studies from large trials compared auto-HCT with chemotherapy. A comparison was made also with allogeneic hematopoietic cell transplantation (allo-HCT). These studies reported a lower relapse rate with auto-HCT compared with chemotherapy, but without impact on the overall survival. A high transplant-related mortality in that era confounded the relevance of these data...
January 10, 2018: Current Opinion in Hematology
https://www.readbyqxmd.com/read/29323237/racial-differences-in-four-leukemia-subtypes-comprehensive-descriptive-epidemiology
#14
Yinjun Zhao, Yu Wang, Shuangge Ma
Leukemia is a malignant progressive disease and has four major subtypes. Different racial groups differ significantly in multiple aspects. Our goal is to systematically and comprehensively quantify racial differences in leukemia. The SEER database is analyzed, and comprehensive descriptive analysis is provided for the four major subtypes, namely ALL (acute lymphoblastic leukemia), CLL (chronic lymphoblastic leukemia), AML (acute myeloid leukemia), and CML (chronic myeloid leukemia), and for two age groups (≤14 and >14) separately...
January 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29321824/high-frequency-of-cd34-cd38-low-immature-leukemia-cells-is-correlated-with-unfavorable-prognosis-in-acute-myeloid-leukemia
#15
Adriana Plesa, Charles Dumontet, Eve Mattei, Ines Tagoug, Sandrine Hayette, Pierre Sujobert, Isabelle Tigaud, Marie Pierre Pages, Youcef Chelghoum, Fiorenza Baracco, Helene Labussierre, Sophie Ducastelle, Etienne Paubelle, Franck Emmanuel Nicolini, Mohamed Elhamri, Lydia Campos, Claudiu Plesa, Stéphane Morisset, Gilles Salles, Yves Bertrand, Mauricette Michallet, Xavier Thomas
AIM: To evaluate the importance of the CD34+CD38- cell population when compared to the CD34+CD38+/low and CD34+CD38+/high leukemic cell sub-populations and to determine its correlations with leukemia characteristics and known prognostic factors, as well as with response to therapy and survival. METHODS: Two hundred bone marrow samples were obtained at diagnosis from 200 consecutive patients with newly diagnosed acute myeloid leukemia (AML) were studied between September 2008 and December 2010 at our Institution (Hematology Department, Lyon, France)...
December 26, 2017: World Journal of Stem Cells
https://www.readbyqxmd.com/read/29321554/mutations-in-dnmt3a-u2af1-and-ezh2-identify-intermediate-risk-acute-myeloid-leukemia-patients-with-poor-outcome-after-cr1
#16
Caner Saygin, Cassandra Hirsch, Bartlomiej Przychodzen, Mikkael A Sekeres, Betty K Hamilton, Matt Kalaycio, Hetty E Carraway, Aaron T Gerds, Sudipto Mukherjee, Aziz Nazha, Ronald Sobecks, Christopher Goebel, Donna Abounader, Jaroslaw P Maciejewski, Anjali S Advani
Intermediate-risk acute myeloid leukemia (IR-AML) is a clinically heterogeneous disease, for which optimal post-remission therapy is debated. The utility of next-generation sequencing information in decision making for IR-AML has yet to be elucidated. We retrospectively studied 100 IR-AML patients, defined by European Leukemia Net classification, who had mutational information at diagnosis, received intensive chemotherapy and achieved complete remission (CR) at Cleveland Clinic (CC). The Cancer Genome Atlas (TCGA) data were used for validation...
January 10, 2018: Blood Cancer Journal
https://www.readbyqxmd.com/read/29321210/the-immune-checkpoint-modulator-ox40-and-its-ligand-ox40l-in-nk-cell-immunosurveillance-and-acute-myeloid-leukemia
#17
Tina Nuebling, Carla Emilia Schumacher, Martin Hofmann, Ilona Hagelstein, Benjamin Joachim Schmiedel, Stefanie Maurer, Birgit Federmann, Kathrin Rothfelder, Malte Roerden, Daniela Dorfel, Pascal Schneider, Gundram Jung, Helmut Rainer Salih
The TNF receptor family member OX40 promotes activation and proliferation of T cells, which fuels efforts to modulate this immune checkpoint to reinforce antitumor immunity. Besides T cells, NK cells are a second cytotoxic lymphocyte subset that contributes to antitumor immunity, particularly in leukemia. Accordingly, these cells are being clinically evaluated for cancer treatment through multiple approaches, such as adoptive transfer of ex vivo expanded polyclonal NK cells (pNKC). Here we analyzed whether and how OX40 and its ligand (OX40L) influence NK-cell function and anti-leukemia reactivity...
January 10, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29320902/cd33-splicing-snp-regulates-expression-levels-of-cd33-in-normal-regenerating-monocytes-in-aml-patients
#18
Jatinder K Lamba, Andrew P Voigt, Lata Chauhan, Miyoung Shin, Richard Aplenc, Lisa Eidenschink Brodersen, Alan S Gamis, Soheil Meshinchi, Michael R Loken
No abstract text is available yet for this article.
January 10, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29320732/stabilization-of-nf-%C3%AE%C2%BAb-inducing-kinase-suppresses-mll-af9-induced-acute-myeloid-leukemia
#19
Yan Xiu, Qianze Dong, Qingchang Li, Fengyin Li, Nick Borcherding, Weizhou Zhang, Brendan Boyce, Hai-Hui Xue, Chen Zhao
Canonical NF-κB signaling is constitutively activated in acute myeloid leukemia (AML) stem cells and is required for maintenance of the self-renewal of leukemia stem cells (LSCs). However, any potential role for NF-κB non-canonical signaling in AML has been largely overlooked. Here, we report that stabilization of NF-κB-inducing kinase (NIK) suppresses AML. Mechanistically, stabilization of NIK activates NF-κB non-canonical signaling and represses NF-κB canonical signaling. In addition, stabilization of NIK-induced activation of NF-κB non-canonical signaling upregulates Dnmt3a and downregulates Mef2c, which suppresses and promotes AML development, respectively...
January 9, 2018: Cell Reports
https://www.readbyqxmd.com/read/29318968/the-role-of-dna-repair-pathways-in-aml-chemosensitivity
#20
Elizabeth A Pearsall, Lisa F Lincz, Kathryn Anne Skelding
BACKGROUND: Defects in DNA repair pathways are causal factors for a plethora of solid tumours, but are only just beginning to be explored in haematological malignancies. Genomic instability, including mutations in DNA sequences, chromosomal aneuploidy, translocations and gene amplifications contribute to the development and progression of AML. Prior DNA damaging agent exposure enhances the risk of developing AML, as does inheritance of genetic syndromes that involve alterations in DNA repair pathways...
January 9, 2018: Current Drug Targets
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