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Acute promyelocyte leukemia

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https://www.readbyqxmd.com/read/28529810/molecular-profiling-a-case-of-zbtb16-rara-acute-promyelocytic-leukemia
#1
Stephen E Langabeer, Lisa Preston, Johanna Kelly, Matt Goodyer, Ezzat Elhassadi, Amjad Hayat
Several variant RARA translocations have been reported in acute promyelocytic leukemia (APL) of which the t(11;17)(q23;q21), which results in a ZBTB16-RARA fusion, is the most widely identified and is largely resistant to therapy with all-trans retinoic acid (ATRA). The clinical course together with the cytogenetic and molecular characterization of a case of ATRA-unresponsive ZBTB16-RARA APL is described. Additional mutations potentially cooperating with the translocation fusion product in leukemogenesis have been hitherto unreported in ZBTB16-RARA APL and were sought by application of a next-generation sequencing approach to detect those recurrently found in myeloid malignancies...
2017: Case Reports in Hematology
https://www.readbyqxmd.com/read/28521962/the-functional-roles-of-pml-nuclear-bodies-in-genome-maintenance
#2
REVIEW
Hae Ryung Chang, Anudari Munkhjargal, Myung-Jin Kim, Seon Young Park, Eunyoung Jung, Jae-Ha Ryu, Young Yang, Jong-Seok Lim, Yonghwan Kim
In the nucleus, there are several membraneless structures called nuclear bodies. Among them, promyelocytic leukemia nuclear bodies (PML-NBs) are involved in multiple genome maintenance pathways including the DNA damage response, DNA repair, telomere homeostasis, and p53-associated apoptosis. In response to DNA damage, PML-NBs are coalesced and divided by a fission mechanism, thus increasing their number. PML-NBs also play a role in repairing DNA double-strand breaks (DSBs) by homologous recombination (HR). Clinically, the dominant negative PML-RARα fusion protein expressed in acute promyelocytic leukemia (APL) inhibits the transactivation of downstream factors and disrupts PML function, revealing the tumor suppressor role of PML-NBs...
May 5, 2017: Mutation Research
https://www.readbyqxmd.com/read/28521025/mechanism-of-as2o3-induced-action-potential-prolongation-and-using-hips-cms-to-evaluate-the-rescue-efficacy-of-drugs-with-different-rescue-mechanism
#3
Meng Yan, Lifang Feng, Yanhui Shi, Junnan Wang, Yan Liu, Fengmei Li, Baoxin Li
Arsenic trioxide (As2O3) has been verified as a breakthrough in the management of acute promyelocytic leukemia in recent decades. However, cardiotoxicity, especially long QT syndrome (LQTS) has become the most important issue during As2O3 treatment. The characterized mechanisms behind this adverse effect are inhibition of cardiac hERG channel trafficking and increase of cardiac calcium currents. In our study, we found a new pathway underlying As2O3-induced cardiotoxicity that As2O3 accelerates lysosomal degradation of hERG on plasma membrane after using brefeldin A (BFA) to block protein trafficking...
May 17, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28507443/erratum-retinoic-acid-and-arsenic-trioxide-in-the-treatment-of-acute-promyelocytic-leukemia-current-perspectives-corrigendum
#4
(no author information available yet)
[This corrects the article on p. 1585 in vol. 10, PMID: 28352191.].
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28502306/-detection-and-analysis-of-immune-molecules-in-leukemia-cell-surfaces-of-acute-promyelocytic-leukemia
#5
Ting Dong, Yaxian Jiang, Zhengfa Li, Hongmei Ouyang, Qin Zhang
Objective To investigate the immunophenotypic characteristics of acute promyelocytic leukemia (APL) and its clinical significance. Methods Immunophenotyping was performed by four-color flow cytometry with CD45/SSC-lin gating for neoplastic cells and was divided into five levels according to the intensity of antigen expression. Results The expression intensity and percentage of typical APL phenotypes were: myeloperoxidase (MPO) and CD33 were consistently expressed (100%); CD38 (82.35%), CD13 (64.71%), CD64 (50%), CD123 (47...
May 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28498435/plumbagin-enhances-trail-induced-apoptosis-of-human-leukemic-kasumi%C3%A2-1-cells-through-upregulation-of-trail-death-receptor-expression-activation-of-caspase-8-and-inhibition-of-cflip
#6
Xiaoyang Kong, Jing Luo, Tongpeng Xu, Yunjiao Zhou, Zengkai Pan, Yinghua Xie, Limin Zhao, Yingting Lu, Xiyao Han, Zhixiong Li, Ligen Liu
Although the patients with t(8;21) acute myeloid leukemia (AML) have a favorable prognosis compared with other non-acute promyelocytic leukemia AML patients, only ~50% patients with this relatively favorable subtype can survive for 5 years and refractory/relapse is common in clinical practice. So it is necessary to find novel agents to treat this type of AML. In this study, the effects and the mechanisms of plumbagin and recombinant soluble tumor necrosis factor‑α-related apoptosis-inducing ligand (rsTRAIL) on leukemic Kasumi‑1 cells were primarily investigated...
May 4, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28496950/development-of-flow-cytometry-fluorescent-in-situ-hybridization-flow-fish-method-for-detection-of-pml-rara-chromosomal-translocation-in-acute-promyelocytic-leukemia-cell-line
#7
Fatemeh Zahedipour, Reza Ranjbaran, Abbas Behzad Behbahani, Khalil Tavakol Afshari, Mohammad Ali Okhovat, Gholamhossein Tamadon, Sedigheh Sharifzadeh
BACKGROUND: Acute Promyelocytic Leukemia (APL) is a subclass of acute myeloid leukemia. The chromosomal aberration in 95% of APL cases is t(15; 17) (q22; q21), which prevents cell differentiation. Characterization of the underlying molecular lesion is valuable in determining optimal treatment strategy. The goal of this study was to develop a new and powerful Flow- FISH technique to detect the long isoform (L) of PML-RARa fusion transcript in NB4 cell line. METHODS: To achieve the best condition for fixation, two different fixatives including 2% paraformaldehyde and 75% ethanol were used...
April 2017: Avicenna Journal of Medical Biotechnology
https://www.readbyqxmd.com/read/28494415/studies-on-curative-efficacy-of-monoterpene-eugenol-on-anti-leukemic-drug-arsenic-trioxide-induced-cardiotoxicity
#8
Prakash Binu, Nellikunnath Priya, Surendran Abhilash, Radhakrishnan Chandraprabha Vineetha, Raveendran Harikumaran Nair
BACKGROUND: Arsenic trioxide (As2O3) is emerging as a frontline agent for the treatment of acute promyelocytic leukemia (APL) but the therapeutic application is limited by its toxicity. QT prolongation, torsades de pointes and sudden cardiac death have been implicated in the As2O3 therapy. So eugenol is a monoterpene compound is well known for its antioxidant properties and protective effect on the cardiovascular system. OBJECTIVE: In this study, the cardioprotective effect of eugenol on cardiac electrical conductivity, tissue electrolytes, myocardial markers, antioxidant system, lipid peroxidation and nitric oxide production was investigated in male Wistar rats treated with arsenic trioxide...
May 7, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28492552/all-trans-retinoic-acid-and-arsenic-trioxide-fail-to-derepress-the-monocytic-differentiation-driver-irf8-in-acute-promyelocytic-leukemia-cells
#9
XiangZhen Liu, Juan Chen, ShanHe Yu, Li Yan, HeZhou Guo, JianMin Dai, Wu Zhang, Jiang Zhu
All-trans retinoic acid (ATRA) and/or arsenic trioxide (ATO) administration leads to granulocytic maturation and/or apoptosis of acute promyelocytic leukemia (APL) cells mainly by targeting promyelocytic leukemia/retinoic acid receptor alpha (PML/RARα). Yet, ~10-15% of APL patients are not cured by ATRA- and ATO-based therapies, and a potential failure of ATRA and ATO in completely reversing PML/RARα-driven oncogenic alterations has not been comprehensively examined. Here we characterized the in vivo primary responses of dysregulated genes in APL cells treated with ATRA and ATO using a GFP-labeled APL model...
May 11, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28491690/dexamethasone-suppresses-long-qt-phenotype-in-patient-with-acute-promyelocytic-leukemia-treated-with-arsenic
#10
Jeffrey R Winterfield, David J Milan
No abstract text is available yet for this article.
July 2016: HeartRhythm Case Reports
https://www.readbyqxmd.com/read/28490888/maintenance-therapy-with-all-trans-retinoic-acid-and-arsenic-trioxide-improves-relapse-free-survival-in-adults-with-low-to-intermediate-risk-acute-promyelocytic-leukemia-who-have-achieved-complete-remission-after-consolidation-therapy
#11
Bin Liang, Zhouyi Zheng, Yifen Shi, Jingjing Chen, Xudong Hu, Honglan Qian, Zhijian Shen, Songfu Jiang, Kang Yu, Jianhua Feng
BACKGROUND: Currently, the optimal maintenance therapy for patients with acute promyelocytic leukemia (APL) who have achieved complete remission (CR) after completing consolidation chemotherapy remains controversial. The comparative effectiveness of the all-trans retinoic acid (ATRA) plus arsenic trioxide (As2O3) maintenance strategy with classic ATRA plus chemotherapy has not been evaluated. In this study, we compared the efficacy and toxicity of maintenance therapy with ATRA plus As2O3 and classic ATRA plus chemotherapy in low- to intermediate-risk APL patients reaching the first CR after induction and consolidation therapy...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28486108/trib3-promotes-apl-progression-through-stabilization-of-the-oncoprotein-pml-rar%C3%AE-and-inhibition-of-p53-mediated-senescence
#12
Ke Li, Feng Wang, Wen-Bin Cao, Xiao-Xi Lv, Fang Hua, Bing Cui, Jiao-Jiao Yu, Xiao-Wei Zhang, Shuang Shang, Shan-Shan Liu, Jin-Mei Yu, Ming-Zhe Han, Bo Huang, Ting-Ting Zhang, Xia Li, Jian-Dong Jiang, Zhuo-Wei Hu
Acute promyelocytic leukemia (APL) is driven by the oncoprotein PML-RARα, which antagonizes myeloid differentiation and promotes APL-initiating cell self-renewal. Combined all-trans retinoic acid (ATRA) with arsenic trioxide (As2O3) or chemotherapy dramatically improves the prognosis of APL patients. Here we report that expression of pseudokinase Tribble 3 (TRIB3) associates positively with APL progression and therapeutic resistance. The elevated TRIB3 expression promotes APL by interacting with PML-RARα and suppressing its sumoylation, ubiquitylation, and degradation...
May 8, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28486101/the-tribble-with-apl-a-new-road-to-therapy
#13
Ruaidhrí Carmody, Karen Keeshan
The t(15;17) translocation generates a PML-RARα fusion protein causative for acute promyelocytic leukemia (APL). Li et al. now identify the pseudokinase stress protein TRIB3 as an important factor in APL disease progression and therapy resistance. Targeting the interaction of TRIB3 and PML-RARα using peptide technology provides a novel therapeutic approach.
May 8, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28480800/combined-chemotherapy-for-acute-promyelocytic-leukemia-a-meta-analysis
#14
Xueliang Li, Chao Wang, Guanglong Chen, Buqiang Ji, Yongchang Xu
BACKGROUND: This study evaluates the efficacy of combined chemotherapy for the management of acute promyelocytic leukemia (APL). METHOD: Literature search was carried out in several electronic databases. Meta-analyses were performed to achieve weighted effect sizes of overall survival (OS), disease-free survival (DFS), complete remission (CR) rate, and relapse rate. Metaregression analyses were performed to evaluate the factors affecting CR and relapse rates. RESULTS: Data from 37 studies (7566 patients) were used for meta-analysis...
May 7, 2017: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/28476193/molecular-characterization-of-pediatric-acute-myeloid-leukemia-results-of%C3%A2-a-multicentric-study-in-brazil
#15
Francianne Gomes Andrade, Elda Pereira Noronha, Gisele Dallapicola Brisson, Filipe Dos Santos Vicente Bueno, Ingrid Sardou Cezar, Eugênia Terra-Granado, Luiz Claudio Santos Thuler, Maria S Pombo-de-Oliveira
BACKGROUND AND AIMS: The biological characterization of childhood acute myeloid leukemia (c-AML) is an important outcome predictor. In Brazil, very little is known about the frequency of AML subgroups, although c-AML accounts for about 18% of leukemias. We carried out this study to investigate the contribution of type I and II gene mutations in the probability of overall survival (pOS) of c-AML in Brazil. METHODS: Seven hundred and three de novo pediatric AML cases (2000-2015) were assessed throughout a multicentric network study...
November 2016: Archives of Medical Research
https://www.readbyqxmd.com/read/28475434/enhancing-acute-myeloid-leukemia-therapy-monitoring-response-using-residual-disease-testing-as-a-guide-to-therapeutic-decision-making
#16
Benjamin Tomlinson, Hillard M Lazarus
Current standards for monitoring the response of acute myeloid leukemia (AML) are based on morphologic assessments of the bone marrow and recovery of peripheral blood counts. A growing experience is being developed to enhance the detection of small amounts of AML, or minimal residual disease (MRD). Areas covered: Available techniques include multi-color flow cytometry (MFC) of leukemia associated immunophenotypes (LAIP), quantitative reverse transcriptase polymerase chain reaction (QRT-PCR) for detecting fusion and mutated genes (RUNX1-RUNX1T1, CBFB-MYH11, and NPM1), overexpression of genes such as WT1, and next generation sequencing (NGS) for MRD...
May 12, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28474970/ellagic-acid-protects-against-arsenic-trioxide-induced-cardiotoxicity-in-rat
#17
A A Hemmati, S Olapour, H Najafzadeh Varzi, M J Khodayar, M Dianat, B Mohammadian, H Yaghooti
Arsenic trioxide (As2O3) is utilized for treating patients suffering from hematological malignancies particularly acute promyelocytic leukemia. Unfortunately, the extensive application of this chemotherapeutic agent has been limited due to its adverse effects such as cardiotoxicity. Ellagic acid, as a phenolic compound, has shown to exert antioxidant, anti-inflammatory, antifibrotic, and antiatherogenic properties. It is also capable of protecting against drug toxicity. In this study, we evaluated whether ellagic acid can protect against As2O3-induced heart injury in rats...
January 1, 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/28471454/diptoindonesin-g-promotes-erk-mediated-nuclear-translocation-of-p-stat1-ser727-and-cell-differentiation-in-aml-cells
#18
Jian Gao, Minmin Fan, Gang Xiang, Jujuan Wang, Xiong Zhang, Wenjie Guo, Xuefeng Wu, Yang Sun, Yanhong Gu, Huiming Ge, Renxiang Tan, Hongxia Qiu, Yan Shen, Qiang Xu
Exploration of a new differentiation therapy that extends the range of differentiation for treating acute myeloid leukemia (AML) is attractive to researchers and clinicians. Here we report that diptoindonesin G (Dip G), a natural resveratrol aneuploid, exerts antiproliferative activity by inducing G2/M phase arrest and cell differentiation in AML cell lines and primary AML cells. Gene-profiling experiments showed that treating human leukemia HL-60 cells with Dip G was associated with a remarkable upregulation of STAT1 target gene expression, including IFIT3 and CXCL10...
May 4, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28469869/central-nervous-system-involvement-of-acute-promyelocytic-leukemia-three-case-reports
#19
Aya Furuya, Masahiro Kawahara, Mina Kumode, Yasuyuki Ohira, Asako Usui, Shiho Nagai, Sakura Hosoba, Hitoshi Minamiguchi, Katsuyuki Kito, Akira Andoh
Central nervous system (CNS) involvement of acute promyelocytic leukemia (APL) causes poor prognosis. Our three cases show that CNS can be involved at the first hematological recurrence, but predicting this is difficult. Triple intrathecal treatment and craniospinal irradiation were effective, while arsenic oxide failed to prevent and improve CNS involvement.
May 2017: Clinical Case Reports
https://www.readbyqxmd.com/read/28468101/-a-case-report-of-secondary-acute-promyelocytic-leukemia-after-treatment-of-translating-to-small-cell-lung-cancer-in-lung-adenocarcinoma
#20
L M Xia, M H Luo, Y L Jiang, Q Zheng, L L Cui, Y Y Zhou
No abstract text is available yet for this article.
April 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
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