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Acute promyelocytic leukemia

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https://www.readbyqxmd.com/read/28823055/effectivity-of-a-modified-sanz-risk-model-for-early-death-prediction-in-patients-with-newly-diagnosed-acute-promyelocytic-leukemia
#1
Yinjun Lou, Yafang Ma, Jianai Sun, Sansan Suo, Hongyan Tong, Wenbin Qian, Wenyuan Mai, Haitao Meng, Jie Jin
Early death is the main obstacle for the cure of patients with acute promyelocytic leukemia (APL). We have analyzed risk factors of early death from 526 consecutive newly diagnosed APL patients between 2004 and 2016. The overall incidence of early death was 7.2% (38/526). The peak hazard of early death occurred in the first 0-3 days. Multivariate logistic analysis demonstrated white blood cell (WBC) counts [odds ratio (OR) = 1.039; 95% confidence interval (CI): 1.024-1.055; P < 0.001], age (OR = 1...
August 19, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28814164/cpx-351-in-acute-myeloid-leukemia-can-a-new-formulation-maximize-the-efficacy-of-old-compounds
#2
Claudia Brunetti, Luisa Anelli, Antonella Zagaria, Giorgina Specchia, Francesco Albano
The management of Acute Myeloid Leukemia (AML) (with the exception of acute promyelocytic leukemia) has remained largely unchanged over the past 40 years. In particular, patients defined as high-risk, according to the 2017 European Leukemia Net recommendations, represent a subgroup with poor response to current therapies that are frequently associated with high-grade toxicity and potentially fatal complications. Areas covered: Preliminary results from an ongoing phase III clinical trial suggest that CPX-351 could represent an interesting treatment option in both induction and "bridge-to-transplant" settings...
August 17, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28810326/-the-analysis-of-prognosis-associated-factors-in-adults-with-acute-promyelocytic-leukemia
#3
R J Ma, Z M Zhu, X L Yuan, L Jiang, S W Yang, J Yang, J M Guo, J Shi, P C Lei, L Zhang, B J Shang, K Sun, Y P Zhai, W Li, Y Zhang
Objective: To explore the prognostic value of CD34, CD2, CD56 expressions and FLT3-ITD mutation in adults with acute promyelocytic leukemia (APL) . Methods: The immuno-phenotypic and molecular characteristics of 137 adult patients with APL (from January 2010 to March 2016, in Henan Provincial People's Hospital) were investigated. And the relationships between CD34, CD2, CD56 expressions, FLT3-ITD mutation and the outcomes of high WBC counts at onset, complete remission (CR) rate, early mortality, relapse rate (RR) , overall survival (OS) , disease free survival (DFS) were explored...
July 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28809551/direct-speciation-analysis-of-arsenic-in-whole-blood-and-blood-plasma-at-low-exposure-levels-by-hydride-generation-cryotrapping-inductively-coupled-plasma-mass-spectrometry
#4
Tomáš Matoušek, Zhifeng Wang, Christelle Douillet, Stanislav Musil, Miroslav Stýblo
A method for analysis of toxicologically important arsenic species in blood plasma and whole blood by selective hydride generation with cryotrapping (HG-CT) coupled either to atomic absorption (AAS) with a quartz multiatomizer or to inductively coupled plasma mass spectrometry (ICP-MS) has been validated. Sample preparation which involved only 5 times dilution with addition of Triton X-100, Antifoam B and L-cysteine suppressed excessive foaming in a hydride generator. Calibration slopes for whole blood and blood plasma spiked with arsenate, monomethylarsonate and dimethylarsinate at 0...
August 15, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28808212/recent-advances-in-arsenic-trioxide-encapsulated-nanoparticles-as-drug-delivery-agents-to-solid-cancers
#5
Anam Akhtar, Scarlet Xiaoyan Wang, Lucy Ghali, Celia Bell, Xuesong Wen
Since arsenic trioxide was first approved as the front line therapy for acute promyelocytic leukemia 25 years ago, its anti-cancer properties for various malignancies have been under intense investigation. However, the clinical successes of arsenic trioxide in treating hematological cancers have not been translated to solid cancers. This is due to arsenic's rapid clearance by the body's immune system before reaching the tumor site. Several attempts have henceforth been made to increase its bioavailability toward solid cancers without increasing its dosage albeit without much success...
January 19, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28804680/treatment-of-older-patients-with-acute-myeloid-leukemia-aml-revised-canadian-consensus-guidelines
#6
REVIEW
Joseph M Brandwein, Nancy Zhu, Rajat Kumar, Brian Leber, Mitchell Sabloff, Irwindeep Sandhu, Jeannine Kassis, Harold J Olney, Mohamed Elemary, Andre C Schuh
The treatment of acute myeloid leukemia (AML) in older patients is undergoing rapid changes, with a number of important publications in the past five years. Because of this, a group of Canadian leukemia experts has produced an update to the Canadian Consensus Guidelines that were published in 2013, with several new agents recommended, subject to availability. Recent studies have supported the survival benefit of induction chemotherapy for patients under age 80, except those with major co-morbidities or those with adverse risk cytogenetics who are not candidates for allogeneic hematopoietic stem cell transplantation (HSCT)...
2017: American Journal of Blood Research
https://www.readbyqxmd.com/read/28800701/a-new-indole-derivative-decreased-sall4-gene-expression-in-acute-promyelocytic-leukemia-cell-line-nb4
#7
Zahra Sheikhrezaei, Parisa Heydari, Alireza Farsinezhad, Ahmad Fatemi, Soudeh Khanamani Falahati-Pour, Shokoofeh Darakhshan, Mojgan Noroozi Karimabad, Ali Darekordi, Hossein Khorramdelazad, Gholamhossein Hassanshahi
Background: Acute myeloblastic leukemia (AML) is a clonal disorder due to bone marrow failure and uncontrolled proliferation of myeloid lineage. Acute promyelocytic leukemia (APL) is a subtype of AML. Heterocyclic compounds, such as indole, are considered as attractive candidates for cancer therapy, due to their abundance in nature and known biological activity. Sal-like protein (SALL4) is a zinc finger transcription factor involving in the multi-potency of stem cells, in the NB4 cell line...
August 12, 2017: Iranian Biomedical Journal
https://www.readbyqxmd.com/read/28800422/cytotoxic-lanostane-triterpenoids-from-the-fruiting-bodies-of-piptoporus-betulinus
#8
Zeynep Tohtahon, Jingjing Xue, Jianxin Han, Yushuang Liu, Huiming Hua, Tao Yuan
Chemical investigation of a bioactive methanolic extract of the fruiting bodies of Piptoporus betulinus led to the isolation of five previously undescribed lanostane triterpenoids named piptolinic acids A-E, as well as five known lanostane triterpenoids. Their structures were elucidated on the basis of 1D and 2D NMR spectroscopic and HRESIMS analysis. Piptolinic acid A with an unusual moiety (3-hydroxy-4-methoxycarbonyl-3-methylbutyryloxy) at C-3 exhibited comparable cytotoxic activity against human promyelocytic leukemia cell line HL-60 (IC50 = 1...
August 8, 2017: Phytochemistry
https://www.readbyqxmd.com/read/28776567/-retinoic-acid-and-arsenic-trioxide-sensitize-acute-promyelocytic-leukemia-cells-to-er-stress
#9
S Masciarelli, E Capuano, T Ottone, M Divona, S De Panfilis, C Banella, N I Noguera, A Picardi, G Fontemaggi, G Blandino, F Lo-Coco, F Fazi
Retinoic acid (RA) in association with chemotherapy or with arsenic trioxide (ATO) results in high cure rates of acute promyelocytic leukemia (APL). We show that RA-induced differentiation of human leukemic cell lines and primary blasts dramatically increases their sensitivity to ER stress- inducing drugs at doses that are not toxic in the absence of RA. In addition, we demonstrate that the PERK pathway, triggered in response to ER stress, plays a major protective role. Moreover, low amounts of pharmacologically induced ER stress, are sufficient to strongly increase ATO toxicity...
August 4, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28768059/-epicatechin-rescues-the-as2-o3-induced-herg-k-channel-deficiency-possibly-through-upregulating-transcription-factor-sp1-expression
#10
Zengxiang Dong, Yuanqi Shi, Lifang Feng, Zhaoqian Shen, Li Fang, Sijia Zheng, Xin Hai, Baoxin Li
(-)-Epicatechin (EPI) has beneficial effects on the cardiovascular disease. The human ether-a-go-go-related gene (HERG) potassium channel is crucial for repolarization of cardiac action potential. Dysfunction of the HERG channel can cause long QT syndrome type 2 (LQT2). Arsenic trioxide (As2 O3 ) has shown efficacy in the treatment of acute promyelocytic leukemia. However, As2 O3 can induce the deficiency of HERG channel and cause LQT2. In this study, we examined whether EPI could rescue the As2 O3 -induced HERG channel deficiency...
August 2, 2017: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/28767288/arsenic-trioxide-consolidation-allows-anthracycline-dose-reduction-for-pediatric-patients-with-acute-promyelocytic-leukemia-report-from-the-children-s-oncology-group-phase-iii-historically-controlled-trial-aaml0631
#11
Matthew A Kutny, Todd A Alonzo, Robert B Gerbing, Yi-Cheng Wang, Susana C Raimondi, Betsy A Hirsch, Cecilia H Fu, Soheil Meshinchi, Alan S Gamis, James H Feusner, John J Gregory
Purpose The Children's Oncology Group AAML0631 trial for newly diagnosed pediatric acute promyelocytic leukemia (APL) was a phase III historically controlled trial to determine the survival of patients receiving arsenic trioxide (ATO) consolidation and reduced doses of anthracyclines. Patients and Methods Patients age 2 to 21 years with de novo APL confirmed by PML-RARα polymerase chain reaction were stratified as standard risk (SR) or high risk (HR) on the basis of diagnostic WBC count. All patients received all-trans retinoic acid (ATRA) during induction, each consolidation course, and maintenance...
August 2, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28766684/epigallocatechin-3-gallate-promotes-all-trans-retinoic-acid-induced-maturation-of-acute-promyelocytic-leukemia-cells-via-pten
#12
Shifei Yao, Liang Zhong, Min Chen, Yi Zhao, Lianwen Li, Lu Liu, Ting Xu, Chunlan Xiao, Liugen Gan, Zhiling Shan, Beizhong Liu
Acute promyelocytic leukemia (APL) is a distinctive subtype of acute myeloid leukemia (AML) in which the hybrid protein promyelocytic leukemia protein/retinoic acid receptor α (PML/RARα) acts as a transcriptional repressor impairing the expression of genes that are critical to myeloid cell mutation. We aimed at explaining the molecular mechanism of green tea polyphenol epigallocatechin-3-gallate (EGCG) enhancement of ATRA-induced APL cell line differentiation. Tumor suppressor phosphatase and tensin homolog (PTEN) was found downregulated in NB4 cells and rescued by proteases inhibitor MG132...
September 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28760054/successful-treatment-of-a-patient-with-acute-promyelocytic-leukemia-with-a-stat5b-rara-fusion-gene-using-decitabine
#13
Anyou Wang, Xiaoyan Cai, Ping Qiang, Qiaohong Duan
No abstract text is available yet for this article.
August 1, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28754375/an-evaluation-of-myeloperoxidase-mediated-bio-activation-of-nsaids-in-promyelocytic-leukemia-hl-60-cells-for-potential-cytotoxic-selectivity
#14
Andrew G M Morgan, Dinesh Babu, Karim Michail, Arno G Siraki
Several lines of evidence have pointed towards the potential therapeutic benefit of NSAIDs in cancer therapy. In this study, we have investigated the acute bio-activation of NSAIDs and their metabolites via myeloperoxidase (MPO), a highly-expressed peroxidase enzyme in acute myeloid leukemia. As bio-activation involves the formation of reactive metabolites, we hypothesized that NSAIDs which produced reactive metabolites would be correlated with leukemia cell toxicity. We tested the enzymatic peroxidation of three NSAIDs, namely diclofenac, indomethacin, and naproxen in comparison with their hepatic metabolites, 4'- hydroxydiclofenac (4'-OHD), 5-hydroxydiclofenac (5-OHD), O-desmethyl-N-deschlorobenzoylindomethacin (DMBI), O-desmethylindomethacin (DMI) and O-desmethylnaproxen (ODN)...
July 25, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28750402/zinc-depletion-by-tpen-induces-apoptosis-in-human-acute-promyelocytic-nb4-cells
#15
Bo Zhu, Jiayu Wang, Feng Zhou, Yingting Liu, Yueyang Lai, Jie Wang, Xiao Chen, Dianhua Chen, Lan Luo, Zi-Chun Hua
BACKGROUND/AIMS: The effects of zinc signaling on proliferation or apoptosis of leukemia cells remain elusive. In the present study, we used N, N, N', N'-tetrakis-(2-pyridylmethyl)-ethylene-diamine (TPEN), a membrane-permeable zinc chelator, to evaluate the effect of zinc depletion on survival and apoptosis of NB4 acute promyelocytic leukemia (APL) cells. METHODS: The pro-apoptotic effects of TPEN on NB4 cells were examined by flow cytometry, and observed using an optical microscope...
July 27, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28743050/pml-rar%C3%AE-stabilized-by-zinc-in-human-acute-promyelocytic-leukemia-nb4-cells
#16
Bo Zhu, Jia-Yu Wang, Jun-Jie Zhou, Feng Zhou, Wei Cheng, Ying-Ting Liu, Jie Wang, Xiao Chen, Dian-Hua Chen, Lan Luo, Zi-Chun Hua
Acute promyelocytic leukemia (APL) is characterized and driven by the promyelocytic leukemia protein-retinoic acid receptor alpha (PML-RARα) fusion gene. Previous studies have highlighted the importance of PML-RARα degradation in the treatment against APL. Considering the presence of two zinc fingers in the PML-RARα fusion protein, we explored the function of zinc homeostasis in maintaining PML-RARα stability. We demonstrated for the first time that zinc depletion by its chelator N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) triggered PML-RARα degradation in NB4 APL cells via the proteasome pathway rather than the autophagy-lysosomal pathway...
July 19, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28740552/npm1-mutant-mediated-pml-delocalization-and-stabilization-enhances-autophagy-and-cell-survival-in-leukemic-cells
#17
Qin Zou, Shi Tan, Zailin Yang, Qian Zhan, Hongjun Jin, Jingrong Xian, Shuaishuai Zhang, Liyuan Yang, Lu Wang, Ling Zhang
Accumulating evidence has defined nucleophosmin 1 (NPM1) mutation as a driver genetic event in acute myeloid leukemia (AML), whereas the pathogenesis of NPM1-mutated AML remains to be fully elucidated. In this study, we showed that mutant NPM1 elevated autophagic activity and autophagic activation contributed to leukemic cell survival in vitro. Meanwhile, we also found high expression of promyelocytic leukemia gene (PML) and its cytoplasmic dislocation in primary NPM1-mutated AML blasts and NPM1-mA positive OCI-AML3 cells...
2017: Theranostics
https://www.readbyqxmd.com/read/28735889/acute-promyelocytic-leukemia-a-perspective
#18
Farhad Ravandi, Richard Stone
Treatment of patients with acute promyelocytic leukemia has significantly improved with the introduction of target specific agents all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) with long term survival a reality for the majority of patients. This can serve as a paradigm for cancer therapy where with the introduction of more potent target-specific drugs our reliance on the traditional cytotoxic agents is likely to diminish and less toxic and more effective regimens are likely to replace the current intensive chemotherapy regimens...
July 6, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28730166/impact-of-chromosomal-rearrangement-upon-dna-methylation-patterns-in-leukemia
#19
Hyang-Min Byun, Shahrooz Eshaghian, Dan Douer, Jonathen Trent, Guillermo Garcia-Manero, Ravi Bhatia, Kim Siegmund, Allen S Yang
Genomic instability, including genetic mutations and chromosomal rearrangements, can lead to cancer development. Aberrant DNA methylation occurs commonly in cancer cells. The aim of this study is to determine the effects of a specific chromosomal lesion the BCR-ABL translocation t(9:22), in establishing DNA methylation profiles in cancer. Materials and methods We compared DNA methylation of 1,505 selected promoter CpGs in chronic myelogenous leukemia (CML), acute lymphoblastic leukemia (ALL) with and without the Philadelphia chromosome t(9:22), CD34+ hematopoietic stem cells transfected with BCR-ABL, and other tumors without BCR-ABL (acute promyelocytic leukemia (APL) and gastrointestinal stromal tumors (GIST)...
2017: Open Medicine (Warsaw, Poland)
https://www.readbyqxmd.com/read/28722470/novel-potent-inhibitors-of-the-histone-demethylase-kdm1a-lsd1-orally-active-in-a-murine-promyelocitic-leukemia-model
#20
Paolo Trifirò, Anna Cappa, Silvia Brambillasca, Oronza A Botrugno, Maria Rosaria Cera, Roberto Dal Zuffo, Paola Dessanti, Giuseppe Meroni, Florian Thaler, Manuela Villa, Saverio Minucci, Ciro Mercurio, Mario Varasi, Paola Vianello
BACKGROUND: Histone lysine demethylases (KDMs) are well-recognized targets in oncology drug discovery. They function at the post-translation level controlling chromatin conformation and gene transcription. KDM1A is a flavin adenine dinucleotide-dependent amine oxidase, overexpressed in several tumor types, including acute myeloid leukemia, neuroblastoma and non-small-cell lung cancer. Among the many known monoamine oxidase inhibitors screened for KDM1A inhibition, tranylcypromine emerged as a moderately active hit, which irreversibly binds to the flavin adenine dinucleotide cofactor...
July 2017: Future Medicinal Chemistry
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