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https://www.readbyqxmd.com/read/28098170/targeting-the-pi3k-akt-pathway-via-gli1-inhibition-enhanced-the-drug-sensitivity-of-acute-myeloid-leukemia-cells
#1
Hui Liang, Qi-Li Zheng, Peng Fang, Jian Zhang, Tuo Zhang, Wei Liu, Min Guo, Christopher L Robinson, Shui-Bing Chen, Xiao-Ping Chen, Fang-Ping Chen, Hui Zeng
Combination targeted therapy is commonly used to treat acute myeloid leukemia (AML) patients, particularly in refractory/relapse (RR) population. However, concerns have been raised regarding the safety and patient tolerance of combination chemotherapy. It is critical to choose the appropriate treatment for precision therapy. We performed genome-wide RNA profiling using RNA-Seq to compare the RR group and the complete remission (CR) group (a total of 42 adult AML patients). The Hedgehog (Hh) and PI3K/AKT pathways were upregulated in the RR population, which was further confirmed by western blot and/or qPCR...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28097942/cd25-as-an-adverse-prognostic-factor-in-elderly-patients-with-acute-myeloid-leukemia
#2
Shin-Ichiro Fujiwara, Kazuo Muroi, Chihiro Yamamoto, Kaoru Hatano, Kiyoshi Okazuka, Kazuya Sato, Iekuni Oh, Ken Ohmine, Takahiro Suzuki, Keiya Ozawa
OBJECTIVES: CD25 has been reported to be highly expressed in leukemia stem cells and correlated with adverse outcomes in young patients with acute myeloid leukemia (AML). However, the significance of CD25 expression in elderly patients with AML has not yet been investigated. METHODS: We retrospectively analyzed 154 newly diagnosed AML patients aged 60 years or over by flow cytometry. RESULTS: CD25-positive AML was characterized by high white blood cell counts, secondary AML, rare favorable karyotypes, and positivity for CD34 and CD7 antigens, compared with CD25-negative AML...
January 18, 2017: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/28092685/precision-oncology-for-acute-myeloid-leukemia-using-a-knowledge-bank-approach
#3
Moritz Gerstung, Elli Papaemmanuil, Inigo Martincorena, Lars Bullinger, Verena I Gaidzik, Peter Paschka, Michael Heuser, Felicitas Thol, Niccolo Bolli, Peter Ganly, Arnold Ganser, Ultan McDermott, Konstanze Döhner, Richard F Schlenk, Hartmut Döhner, Peter J Campbell
Underpinning the vision of precision medicine is the concept that causative mutations in a patient's cancer drive its biology and, by extension, its clinical features and treatment response. However, considerable between-patient heterogeneity in driver mutations complicates evidence-based personalization of cancer care. Here, by reanalyzing data from 1,540 patients with acute myeloid leukemia (AML), we explore how large knowledge banks of matched genomic-clinical data can support clinical decision-making. Inclusive, multistage statistical models accurately predicted likelihoods of remission, relapse and mortality, which were validated using data from independent patients in The Cancer Genome Atlas...
January 16, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28091414/acute-myeloid-leukemia-advancements-in-diagnosis-and-treatment
#4
REVIEW
Meng-Ge Yu, Hu-Yong Zheng
OBJECTIVE: Leukemia is the most common pediatric malignancy and a major cause of morbidity and mortality in children. Among all subtypes, a lack of consensus exists regarding the diagnosis and treatment of acute myeloid leukemia (AML). Patient survival rates have remained modest for the past three decades in AML. Recently, targeted therapy has emerged as a promising treatment. DATA SOURCES: We searched the PubMed database for recently published research papers on diagnostic development, target therapy, and other novel therapies of AML...
2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28088962/-efficacy-and-safety-of-sorafenib-as-monotherapy-to-flt3-itd-positive-acute-myeloid-leukemia
#5
J S Jia, H H Zhu, H X Fu, L Z Gong, J Kong, X J Huang, H Jiang
Objective: To explore the efficacy and safety of Sorafenib as monotherapy to FLT3 positive acute myeloid leukemia (AML). Methods: From April 2014 to December 2015, fourteen AML patients with FLT3 positive, 7 males and 7 females with a median age of 42 (range: 14-81) years old, were enrolled in this study. Of the 14 cases, 4 were de novo cases, 9 refractory cases and 1 relapsed case, including 78.6% patients with severe complications and 57.1% patients with KPS score less than 60 [the median KPS score was 45 (20-70) ]...
December 14, 2016: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28087457/t-cell-replete-peripheral-blood-haploidentical-hematopoietic-cell-transplantation-with-post-transplant-cyclophosphamide-results-in-outcomes-similar-to-traditionally-matched-donors-in-active-disease-acute-myeloid-leukemia
#6
Joan How, Michael Slade, Khoan Vu, John F DiPersio, Peter Westervelt, Geoffrey L Uy, Camille N Abboud, Ravi Vij, Mark A Schroeder, Todd A Fehniger, Rizwan Romee
Outcomes for acute myeloid leukemia (AML) patients who fail to achieve complete remission remain poor. Hematopoietic cell transplantation (HCT) has been shown to induce long-term survival in AML patients with active disease. HCT is largely performed with HLA-matched unrelated or HLA-matched related donors. Recently, HCT with HLA-haploidentical related donors has been identified as a feasible option when HLA-matched donors are not immediately available. However, there is little data comparing outcomes of AML patients with active disease who receive haploidentical versus traditionally matched HCT...
January 10, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28067876/impact-of-wilms-tumor-1-expression-on-outcome-of-patients-undergoing-allogeneic-stem-cell-transplantation-for-aml
#7
R Duléry, O Nibourel, J Gauthier, V Elsermans, H Behal, V Coiteux, L Magro, A Renneville, A Marceau, T Boyer, B Quesnel, C Preudhomme, A Duhamel, I Yakoub-Agha
The monitoring of the minimal residual disease by Wilms' tumor 1 expression (MRD(WT1)) is a standardized test, which can be used in over 80% of patients with AML. To investigate the prognostic value of MRD(WT1) in patients undergoing allogeneic stem cell transplantation (allo-SCT) for AML, MRD(WT1) was monitored 3 months after transplantation in 139 patients. MRD(WT1) positivity did not lead to any therapeutic intervention. Median follow-up was 39.3 (6.4-99.8) months. Patients with positive MRD(WT1) at 3 months experienced more often post-transplant relapse (27/30, 90%) than those with negative MRD(WT1) (16/109, 14...
January 9, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28058490/second-line-azacitidine-for-elderly-or-infirmed-patients-with-acute-myeloid-leukemia-aml-not-eligible-for-allogeneic-hematopoietic-cell-transplantation-a-retrospective-national-multicenter-study
#8
Ron Ram, Moshe Gatt, Drorit Merkel, Ilana Helman, Tsofia Inbar, Arnon Nagler, Irit Avivi, Yishai Ofran
Elderly and infirm patients with acute myeloid leukemia (AML) with either induction refractory or relapse disease may benefit from treatment with azacitidine. We retrospectively reviewed the data from five tertiary centers in Israel, treated between 2009 and 2015. Thirty-four patients (median age 74 years) were identified. Sixty-two percent of the patients had relapsed disease and 38% had refractory disease. Median time of follow-up was 12.1 months. Out of a total of 327 courses, incidence of infectious episodes was 6%...
January 5, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28056398/clinical-outcome-of-myeloid-sarcoma-in-adult-patients-and-effect-of-allogeneic-stem-cell-transplantation-results-from-a-multicenter-survey
#9
Davide Lazzarotto, Anna Candoni, Carla Filì, Fabio Forghieri, Livio Pagano, Alessandro Busca, Giuseppina Spinosa, Maria Elena Zannier, Erica Simeone, Miriam Isola, Erika Borlenghi, Lorella Melillo, Federico Mosna, Federica Lessi, Renato Fanin
INTRODUCTION: Myeloid Sarcoma (MS) is a rare hematologic myeloid neoplasm that can involve any site of the body. It can occur as an exclusively extramedullary form or it can be associated with an acute myeloid leukemia (AML), a chronic myeloproliferative neoplasm (MPN) or a myelodysplastic syndrome (MDS) at onset or at relapse. The rarity of MS does not enable prospective clinical trials and therefore a specific multicenter register can be useful for the clinical and biological studies of this rare disease...
December 20, 2016: Leukemia Research
https://www.readbyqxmd.com/read/28052659/p15ink4b-loss-of-expression-by-promoter-hypermethylation-adds-to-leukemogenesis-and-confers-a-poor-prognosis-in-acute-promyelocytic-leukemia-patients
#10
Shahid M Baba, Niyaz A Azad, Zafar A Shah, Dil- Afroze, Arshad A Pandith, Aleem Jan, Sheikh A Aziz
Purpose: The p15Ink4b gene exerts its influence as an inhibitor of cyclin-dependent kinases and is frequently associated with hematological malignancies. Inactivation of this gene through DNA methylation has been found to be the most prevalent epigenetic alteration reported, with a high frequency in all FAB subtypes of AMLs, including APL. In this study, we investigated the prognostic significance of p15 gene promoter hypermethylation and its expression in APL patients of Kashmir (North India)...
December 5, 2016: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28049642/therapeutic-value-of-clofarabine-in-younger-and-middle-aged-18-65-yrs-adults-with-newly-diagnosed-aml
#11
Bob Löwenberg, Thomas Pabst, Johan Maertens, Yvette van Norden, Bart J Biemond, Harry C Schouten, Olivier Spertini, Edo Vellenga, Carlos Graux, Violaine Havelange, Georgine E de Greef, Okke de Weerdt, Marie-Cecile J C Legdeur, Juergen Kuball, Marinus van Marwijk Kooy, Bjorn T Gjertsen, Mojca Jongen-Lavrencic, Arjan A van de Loosdrecht, Daniëlle van Lammeren-Venema, Beata Hodossy, Dimitri A Breems, Yves Chalandon, Jakob Passweg, Peter J M Valk, Markus G Manz, Gert J Ossenkoppele
Clofarabine has demonstrated antileukemic activity in acute myeloid leukemia (AML) but has yet to be critically evaluated in younger adults in the frontline with standard chemotherapy. We compared two induction regimens in newly diagnosed patients aged 18-65 with AML/high risk MDS, i.e., idarubicine-cytarabine (cycle I) and amsacrine-cytarabine (cycle II) without or with clofarabine (10 mg/m(2) on days 1-5 of each of both cycles). Consolidation involved chemotherapy with or without hematopoietic stem cell transplantation...
January 3, 2017: Blood
https://www.readbyqxmd.com/read/28048817/su-f-t-83-infant-total-skin-electron-therapy-using-five-fields-technique
#12
H Saleh, T Howlin, V Massey
PURPOSE: We were presented with a 9 month old boy with Relapsed Acute Myeloid Leukemia (AML) involving the skin. The plan was to treat the entire skin using 6 MeV electrons with the infant under complete anesthesia. The purpose of this work is to commission the 6 MeV electron beam and to develop a technique that can be used to deliver total skin dose to infants with minimal patient immobilization. METHODS: A baby mannequin phantom that mimics the child's length was used to determine the best technique to treat the infant...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28042875/the-pik3-mtor-dual-inhibitor-bez235-suppresses-proliferation-and-migration-and-reverses-multidrug-resistance-in-acute-myeloid-leukemia
#13
Lan Deng, Ling Jiang, Xiang-Hua Lin, Kuo-Fu Tseng, Yuan Liu, Xing Zhang, Rui-Hong Dong, Zhi-Gang Lu, Xiu-Ju Wang
Aberrant activation of the PI3K/Akt/mTOR pathway contributes to the proliferation of malignant cells, and may confer resistance to chemotherapy in various malignancies, including acute myeloid leukemia (AML). Chemoresistance is the major reason for relapse in AML. RAD001 (everolimus) has been used at d1 and d7 of an induction chemotherapy regimen for AML, which has acceptable toxicity and may improve conventional chemotherapeutic treatment. Dual inhibitors of PI3K and mTOR overcome some of the intrinsic disadvantages of rapamycin and its derivatives...
January 2, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28030834/histone-deacetylases-1-and-2-cooperate-in-regulating-brca1-chk1-and-rad51-expression-in-acute-myeloid-leukemia-cells
#14
Jianyun Zhao, Chengzhi Xie, Holly Edwards, Guan Wang, Jeffrey W Taub, Yubin Ge
Resistance to chemotherapy and a high relapse rate highlight the importance of finding new therapeutic options for the treatment of acute myeloid leukemia (AML). Histone deacetylase (HDAC) inhibitors (HDACIs) are a promising class of drugs for the treatment of AML. HDACIs have limited single-agent clinical activities, but when combined with conventional or investigational drugs they have demonstrated favorable outcomes. Previous studies have shown that decreasing expression of important DNA damage repair proteins enhances standard chemotherapy drugs...
December 21, 2016: Oncotarget
https://www.readbyqxmd.com/read/28028446/a-purely-extradural-lumbar-nerve-root-cavernoma-mimicking-acute-myeloid-leukemia-recurrence-case-report-and-literature-review
#15
Edson Oliveira, José Pedro Lavrador, Joaquim Teixeira, Alexandra Pignatelli, Sérgio Livraghi
BACKGROUND: Myeloid sarcoma (MS) is a malignant tumor that usually occurs concomitantly with or following acute myeloid leukemia (AML). Cavernomas are benign congenital malformations that are unusual in the spine and exceedingly rare in pure extradural locations. CASE DESCRIPTION: We report a 73-year-old female with a previous medical history of AML in remission for 3 years who presented with symptoms of low back pain and right lower extremity radiculopathy. A magnetic resonance scan showed an extradural, foraminal lesion centered at the L2 level involving the right L2 nerve root...
2016: Surgical Neurology International
https://www.readbyqxmd.com/read/27991894/fludarabine-with-pharmacokinetically-guided-iv-busulfan-is-superior-to-fixed-dose-delivery-in-pretransplant-conditioning-of-aml-mds-patients
#16
B S Andersson, P F Thall, B C Valdez, D R Milton, G Al-Atrash, J Chen, A Gulbis, D Chu, C Martinez, S Parmar, U Popat, Y Nieto, P Kebriaei, A Alousi, M de Lima, G Rondon, Q H Meng, A Myers, J Kawedia, L L Worth, M Fernandez-Vina, T Madden, E J Shpall, R B Jones, R E Champlin
We hypothesized that IV busulfan (Bu) dosing could be safely intensified through pharmacokinetic (PK-) dose guidance to minimize the inter-patient variability in systemic exposure (SE) associated with body-sized dosing, and that this should improve outcome of AML/MDS patients undergoing allogeneic stem cell transplantation. To test this hypothesis, we treated 218 patients (median age 50.7 years, male/female 50/50%) with fludarabine 40 mg/m(2) once daily x4, each dose followed by IV Bu, randomized to 130 mg/m(2) (N=107) or PK-guided to average daily SE, AUC of 6000 μM min (N=111), stratified for remission status and allo-grafting from HLA-matched donors...
December 19, 2016: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/27974109/-expression-of-wt1-gene-in-children-with-acute-myeloid-leukemia
#17
Xue Tang, Xia Guo, Xue Yang, Hui Xiao, Jing-Jing Sun, Li-Xing Yuan, Ju Gao
OBJECTIVE: To study WT1 gene expression in children with acute myeloid leukemia (AML) and its possible correlations to clinical outcomes. METHODS: Bone marrow samples were collected from 45 children with AML (excluding acute promyelocytic leukemia, AML-M3) at different time points of AML treatment and follow-up. WT1 gene expression levels in bone marrow mononuclear cells were assayed by real-time fluorescence quantitative PCR. The correlation between WT1 expression and prognosis was retrospectively analyzed...
December 2016: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/27966377/acute-myeloid-leukemia-a-retrospective-claims-analysis-of-resource-utilization-and-expenditures-for-newly-diagnosed-patients-from-first-line-induction-to-remission-and-relapse
#18
William Irish, Michael Ryan, Larry Gache, Candace Gunnarsson, Timothy Bell, Mark Shapiro
OBJECTIVE: The objective of this study was to estimate resource utilization and expenditures for patients with acute myeloid leukemia (AML) in a real-world claims database. RESEARCH DESIGN AND METHODS: AML patients were identified in MarketScan claims databases between 1 January 2009 and 31 January 2015. Patients had a minimum of two AML diagnosis codes, hospitalization within 14 days after initial diagnosis, and ≥6 months of enrollment before initial diagnosis...
December 14, 2016: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/27951719/-molecular-genetic-testing-for-acute-myeloid-leukemia
#19
V Janečková, L Semerád, I Ježíšková, D Dvořáková, M Čulen, Z Šustková, J Mayer, Z Ráčil
BACKGROUND: Acute myeloid leukemia (AML) is a clinically complex and very heterogeneous disease at the molecular level. Conventional cytogenetic analysis and FISH (fluorescence in situ hybridization) tests provide important information about the biological and clinical background of the disease and enable the classification of AML patients into three risk groups. However, up to half of patients have normal cytogenetics. Determining prognosis and treatment strategies in this group of patients is challenging...
2016: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/27941792/loss-of-the-histone-methyltransferase-ezh2-induces-resistance-to-multiple-drugs-in-acute-myeloid-leukemia
#20
Stefanie Göllner, Thomas Oellerich, Shuchi Agrawal-Singh, Tino Schenk, Hans-Ulrich Klein, Christian Rohde, Caroline Pabst, Tim Sauer, Mads Lerdrup, Sigal Tavor, Friedrich Stölzel, Sylvia Herold, Gerhard Ehninger, Gabriele Köhler, Kuan-Ting Pan, Henning Urlaub, Hubert Serve, Martin Dugas, Karsten Spiekermann, Binje Vick, Irmela Jeremias, Wolfgang E Berdel, Klaus Hansen, Arthur Zelent, Claudia Wickenhauser, Lutz P Müller, Christian Thiede, Carsten Müller-Tidow
In acute myeloid leukemia (AML), therapy resistance frequently occurs, leading to high mortality among patients. However, the mechanisms that render leukemic cells drug resistant remain largely undefined. Here, we identified loss of the histone methyltransferase EZH2 and subsequent reduction of histone H3K27 trimethylation as a novel pathway of acquired resistance to tyrosine kinase inhibitors (TKIs) and cytotoxic drugs in AML. Low EZH2 protein levels correlated with poor prognosis in AML patients. Suppression of EZH2 protein expression induced chemoresistance of AML cell lines and primary cells in vitro and in vivo...
January 2017: Nature Medicine
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