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Acute promyelocyte leukemia

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https://www.readbyqxmd.com/read/29166740/-factors-associated-with-early-treatment-response-in-adults-with-acute-myeloid-leukemia
#1
X Ren, T Zhao, J Wang, H H Zhu, H Jiang, J S Jia, S M Yang, B Jiang, D B Wang, X J Huang, Q Jiang
Objective: To explore the factors influencing early treatment responses in adult with de novo acute myeloid leukemia (AML) . Methods: Data of consecutive newly-diagnosed AML (non-acute promyelocytic leukemia) adults were analyzed retrospectively. To assess the impact of clinical characteristics at diagnosis and induction regimen on achieving morphologic leukemia-free state (MLFS) , blood counts and minimal residual leukemia (MRD, positive MRD defined as RQ-PCR WT1 mRNA ≥0.6% and/or any level of abnormal blast population detected by flow cytometry) at the time of achieving MLFS...
October 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/29162478/liposomes-assembled-from-dimeric-retinoic-acid-phospholipid-with-improved-pharmacokinetic-properties
#2
Lu Lu, Yawei Du, Muhammad Ismail, Longbing Ling, Chen Yao, Zhenglin Fu, Xinsong Li
All-trans-retinoic acid (ATRA) exhibits potent cytotoxicities against different cancer cells by binding to retinoic acid receptors (RARs), which is regarded as the first example of targeted therapy in acute promyelocytic leukemia (APL). However, its extensive clinical applications have been limited because of poor aqueous solubility, short half-life time and side effects. In this report, dimeric ATRA phosphorylcholine prodrug (Di-ATRA-PC) was designed and assembled into nanoliposomes to improve its pharmacokinetic properties...
November 18, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29159499/redistribution-of-cell-cycle-by-arsenic-trioxide-is-associated-with-demethylation-and-expression-changes-of-cell-cycle-related-genes-in-acute-promyelocytic-leukemia-cell-line-nb4
#3
Saeed Hassani, Ali Khaleghian, Shahin Ahmadian, Shaban Alizadeh, Kamran Alimoghaddam, Ardeshir Ghavamzadeh, Seyed H Ghaffari
PML-RARα perturbs the normal epigenetic setting, which is essential to oncogenic transformation in acute promyelocytic leukemia (APL). Transcription induction and recruitment of DNA methyltransferases (DNMTs) by PML-RARα and subsequent hypermethylation are components of this perturbation. Arsenic trioxide (ATO), an important drug in APL therapy, concurrent with degradation of PML-RARα induces cell cycle change and apoptosis. How ATO causes cell cycle alteration has remained largely unexplained. Here, we investigated DNA methylation patterns of cell cycle regulatory genes promoters, the effects of ATO on the methylated genes and cell cycle distribution in an APL cell line, NB4...
November 20, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/29141325/-genetic-characteristics-of-acute-promyelocytic-leukemia-and-the-application-of-next-generation-sequencing-technology-in-apl
#4
J Zhao, B S Li, J Y Tang
No abstract text is available yet for this article.
November 2, 2017: Zhonghua Er Ke za Zhi. Chinese Journal of Pediatrics
https://www.readbyqxmd.com/read/29137406/the-forkhead-box-c1-foxc1-transcription-factor-is-downregulated-in-acute-promyelocytic-leukemia
#5
Emiliano Fabiani, Giulia Falconi, Nélida Inés Noguera, Ernestina Saulle, Laura Cicconi, Mariadomenica Divona, Cristina Banella, Alessandra Picardi, Anna Maria Cerio, Letizia Boe, Massimo Sanchez, Elvira Pelosi, Ugo Testa, Francesco Lo-Coco, Maria Teresa Voso
Forkhead box (FOX) genes encode transcription factors, which regulate embryogenesis and play an important role in hematopoietic differentiation and in mesenchymal niche maintenance. Overexpression of the family member FOXC1 has been reported in solid tumors and acute myeloid leukemia (AML). We studied FOXC1 expression and function in acute promyelocytic leukemia (APL) and normal hematopoietic progenitors. FOXC1 mRNA and protein levels were significantly lower in primary marrow samples from 27 APL patients, as compared to samples obtained from 27 patients with other AML subtypes, and 5 normal CD34+ hematopoietic cells...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137304/monocarboxylate-transporter-1-mct1-a-tool-to-stratify-acute-myeloid-leukemia-aml-patients-and-a-vehicle-to-kill-cancer-cells
#6
Filipa Lopes-Coelho, Carolina Nunes, Sofia Gouveia-Fernandes, Rita Rosas, Fernanda Silva, Paula Gameiro, Tânia Carvalho, Maria Gomes da Silva, José Cabeçadas, Sérgio Dias, Luís G Gonçalves, Jacinta Serpa
Dysregulation of glucose/lactate dynamics plays a role in cancer progression, and MCTs are key elements in metabolic remodeling. VEGF is a relevant growth factor in the maintenance of bone marrow microenvironment and it is also important in hematological diseases. Our aim was to investigate the role of VEGF in the metabolic adaptation of Acute myeloid leukemia (AML) cells by evaluating the metabolic profiles and cell features according to the AML lineage and testing lactate as a metabolic coin. Our in vitro results showed that AML promyelocytic (HL60) and monocytic (THP1) (but not erythroid- HEL) lineages are well adapted to VEGF and lactate rich environment...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136503/acute-promyelocytic-leukemia-a-paradigm-for-oncoprotein-targeted-cure
#7
REVIEW
Hugues de Thé, Pier Paolo Pandolfi, Zhu Chen
Recent clinical trials have demonstrated that the immense majority of acute promyelocytic leukemia (APL) patients can be definitively cured by the combination of two targeted therapies: retinoic acid (RA) and arsenic. Mouse models have provided unexpected insights into the mechanisms involved. Restoration of PML nuclear bodies upon RA- and/or arsenic-initiated PML/RARA degradation is essential, while RA-triggered transcriptional activation is dispensable for APL eradication. Mutations of the arsenic-binding site of PML/RARA, but also PML, have been detected in therapy-resistant patients, demonstrating the key role of PML in APL cure...
November 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29128809/icariin-induces-apoptosis-in-acute-promyelocytic-leukemia-by-targeting-pim1
#8
Hong Zhang, Ping Li, Jing Li, Tongguo Song, Lin Wang, Enze Li, Jiao Wang, Luning Wang, Na Wei, Zhi Wang
BACKGROUND: Acute promyelocytic leukemia (APL) is one type of acute myeloid leukemia (AML) featured by abnormal, heavily granulated promyelocytes. This study aimed to investigate the antitumor activity of icariin in APL cells. METHODS: APL cell lines (HL-60 and NB4) were used to investigate the effect of icariin in vitro. Cell viability was determined by WST-8 proliferation assay, while cell apoptosis was assessed by flow cytometry. The mRNA and protein expression was determined by quantitative real-time polymerase chain reaction and Western blot, respectively...
June 15, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/29119387/a-new-etv6-ntrk3-cell-line-model-reveals-malat1-as-a-novel-therapeutic-target-a-short-report
#9
Suning Chen, Stefan Nagel, Bjoern Schneider, Haiping Dai, Robert Geffers, Maren Kaufmann, Corinna Meyer, Claudia Pommerenke, Kenneth S Thress, Jiao Li, Hilmar Quentmeier, Hans G Drexler, Roderick A F MacLeod
BACKGROUND: Previously, the chromosomal translocation t(12;15)(p13;q25) has been found to recurrently occur in both solid tumors and leukemias. This translocation leads to ETV6-NTRK3 (EN) gene fusions resulting in ectopic expression of the NTRK3 neurotropic tyrosine receptor kinase moiety as well as oligomerization through the donated ETV6-sterile alpha motif domain. As yet, no in vitro cell line model carrying this anomaly is available. Here we genetically characterized the acute promyelocytic leukemia (APL) cell line AP-1060 and, by doing so, revealed the presence of a t(12;15)(p13;q25)...
November 8, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/29114972/frontline-therapy-of-acute-promyelocytic-leukemia-randomized-comparison-of-atra-and-intensified-chemotherapy-versus-atra-and-anthracyclines
#10
Eva Lengfelder, Dennis Görlich, Daniel Nowak, Karsten Spiekermann, Claudia Haferlach, Utz Krug, Karl-Anton Kreuzer, Jan Braess, Christoph Schliemann, Hans-Walter Lindemann, Heinz A Horst, Xaver Schiel, Michael Flasshove, Anna Hecht, Susanne Schnittger, Stephanie Schneider, Bernhard Wörmann, Wolf-Karsten Hofmann, Wolfgang E Berdel, Eike Bormann, Cristina Sauerland, Thomas Büchner, Wolfgang Hiddemann
OBJECTIVES: Randomized comparison of two treatment strategies in frontline therapy of acute promyelocytic leukemia (APL): all-trans retinoic acid (ATRA) and double induction intensified by high dose cytosine arabinoside (HD ara-C) (German AMLCG) and therapy with ATRA and anthracyclines (Spanish PETHEMA, LPA99). PATIENTS AND RESULTS: Eighty of 87 adult patients with genetically confirmed APL of all risk groups were eligible. The outcome of both arms was similar: AMLCG vs PETHEMA: hematological complete remission 87% vs 83%, early death 13% vs 17% (p=0...
November 7, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/29113330/flow-cytometric-analysis-of-cd64-expression-pattern-and-density-in-the-diagnosis-of-acute-promyelocytic-leukemia-a-multi-center-study-in-shanghai-china
#11
Min Liu, Xiangqin Weng, Shenglan Gong, Hui Chen, Jing Ding, Mengqiao Guo, Xiaoxia Hu, Jianmin Wang, Jianmin Yang, Gusheng Tang
No unified immunophenotypic profiles and corresponding analytic strategies have been established for the rapid diagnosis of acute promyelocytic leukemia (APL) using flow cytometry (FCM). Here we describe a characteristic immunophenotypic panel that can rapidly and accurately distinguish APL from other types of adult acute myeloid leukemia (AML) using only FCM. By comparing APL cells and non-APL AML cells that share APL common immunophenotypes (CD34(-)CD117(+)HLA(-)DR(-)) we found that CD64 was a significant factor that differentiated APL from other AMLs...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29113283/epigallocatechin-3-gallate-induces-apoptosis-in-acute-promyelocytic-leukemia-cells-via-a-shp-1-p38%C3%AE-mapk-bax-cascade
#12
Liugen Gan, Liang Zhong, Zhiling Shan, Chunlan Xiao, Ting Xu, Hao Song, Liu Li, Rong Yang, Beizhong Liu
Acute promyelocytic leukemia (APL) is characterized by a specific chromosomal translation, resulting in a fusion gene that affects the differentiation, proliferation and apoptosis of APL cells. Epigallocatechin-3-gallate (EGCG), a catechin, exhibits numerous biological functions, including antitumor activities. Previous studies have reported that EGCG induces apoptosis in NB4 cells. However, the molecular mechanism underlying EGCG-induced apoptosis remains unclear. The present study aimed to determine the molecular basis of EGCG-induced apoptosis in NB4 cells...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29113277/sequence-variations-of-mitochondrial-dna-d-loop-region-in-patients-with-acute-myeloid-leukemia
#13
Juan Zhou, Haimei Gou, Yuanxin Ye, Yi Zhou, Xiaojun Lu, Binwu Ying
The aim of the present study was to explore variations of the displacement (D)-loop region in patients with acute myeloid leukemia (AML) and their possible associations with AML pathogenesis. Blood or bone marrow samples from 216 patients with AML (158 AML patients in the first stage, and 58 more patients with AML-M3 for further verification), and 146 healthy controls were collected. Sanger sequencing was performed for the D-loop region ranging between nucleotide (nt)15811 and nt 775. With the exception of mitochondrial microsatellite instability (mtMSI) variations, a total of 2,630 variations in 232 loci were identified with similar variation rates/person in patients with AML and controls when compared with the revised Cambridge reference sequence (8...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29111326/c-ebp%C3%AE-contributes-to-transcriptional-activation-of-long-non-coding-rna-neat1-during-apl-cell-differentiation
#14
Yewei Wang, Lei Fu, Ailian Sun, Doudou Tang, Yunxiao Xu, Zheyuan Li, Mingjie Chen, Guangsen Zhang
Emerging evidences have shown that long non-coding RNAs (lncRNAs) play critical roles in cancer development and cancer therapy. LncRNA Nuclear Enriched Abundant Transcript 1 (NEAT1) is indispensable during acute promyelocytic leukemia (APL) cell differentiation induced by all-trans retinoic acid (ATRA). However, the precise mechanism of NEAT1 upregulation has not been fully understood. In this study, we performed chromatin immunoprecipitation and luciferase reporter assays to demonstrate that C/EBP family transcription factor C/EBPβ bind to and transactivate the promoter of lncRNA NEAT1 through the C/EBPβ binding sites both around -54 bp and -1453 bp upstream of the transcription start site...
October 27, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29110117/successful-treatment-of-acute-promyelocytic-leukemia-in-pregnancy-with-single-agent-all-trans-retinoic-acid
#15
REVIEW
Cordula M Nellessen, Viktor Janzen, Karin Mayer, Giulia Giovannini, Ulrich Gembruch, Peter Brossart, Waltraut M Merz
PURPOSE: The diagnosis of acute promyelocytic leukemia (APL) in pregnancy is an uncommon, life-threatening emergency. Choice of treatment and management of complications are challenging. METHODS: We report the case of a patient with diagnosis of APL at gestational age (GA) 24 + 4. We describe the interdisciplinary management during pregnancy and delivery and provide a 2-year follow-up. Existing reports on APL in pregnancy are summarized. RESULTS: Single-agent induction therapy with all-trans retinoic acid (ATRA) was started and resulted in normalization of blood cell counts after 32 days...
November 6, 2017: Archives of Gynecology and Obstetrics
https://www.readbyqxmd.com/read/29107745/respiratory-syncytial-virus-induces-nrf2-degradation-through-a-promyelocytic-leukemia-protein-ring-finger-protein-4-dependent-pathway
#16
Narayana Komaravelli, Maria Ansar, Roberto P Garofalo, Antonella Casola
Respiratory syncytial virus (RSV) is the most important cause of viral acute respiratory tract infections and hospitalizations in children, for which no vaccine or specific treatments are available. RSV causes airway mucosa inflammation and cellular oxidative damage by triggering production of reactive oxygen species and by inhibiting at the same time expression of antioxidant enzymes, via degradation of the transcription factor NF-E2-related factor 2 (NRF2). RSV infection induces NRF2 deacetylation, ubiquitination, and degradation through a proteasome-dependent pathway...
October 28, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29105243/performance-of-multiplex-fusion-gene-testing-in-pediatric-acute-myeloid-leukemia
#17
Yuka Iijima-Yamashita, Hidemasa Matsuo, Miho Yamada, Takao Deguchi, Nobutaka Kiyokawa, Akira Shimada, Akio Tawa, Hiroyuki Takahashi, Daisuke Tomizawa, Takashi Taga, Akitoshi Kinoshita, Souichi Adachi, Keizo Horibe
BACKGROUND: Gene abnormalities, particularly chromosome rearrangements generating gene fusions, are associated with clinical characteristics and prognosis in pediatric acute myeloid leukemia (AML). Karyotyping is generally performed to enable risk stratification; however, the results are not always consistent with those generated by reverse transcription-polymerase chain reaction (RT-PCR), and more accurate and rapid methods are required. METHODS: A total of 487 samples from de novo AML patients enrolled in the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) AML-05 study (n = 448), and acute promyelocytic leukemia (APL) patients enrolled in the JPLSG AML-P05 study (n = 39) were available for this investigation...
November 4, 2017: Pediatrics International: Official Journal of the Japan Pediatric Society
https://www.readbyqxmd.com/read/29097117/dasatinib-synergizes-with-atra-to-trigger-granulocytic-differentiation-in-atra-resistant-acute-promyelocytic-leukemia-cell-lines-via-lyn-inhibition-mediated-activation-of-raf-1-mek-erk
#18
Ming Ding, Xiang-Qin Weng, Yan Sheng, Jing Wu, Cui Liang, Xun Cai
All-trans retinoic acid (ATRA) resistance has been a critical problem in acute promyelocytic leukemia (APL) relapsed patients. In this study, dasatinib synergized with ATRA to trigger differentiation in ATRA-resistant APL cell lines. The combined treatment activated RAF-1, MEK and ERK as well as enhanced ATRA-promoted up-regulation of the protein level of PU.1, C/EBPβ and C/EBPε. U0126 (MEK specific inhibitor) and sorafenib tosylate (RAF-1 specific inhibitor) suppressed the combined treatment-induced differentiation, ERK phosphorylation and the up-regulation of C/EBPs and PU...
October 30, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29096331/nucleostemin-silencing-induces-differentiation-and-potentiates-all-trans-retinoic-acid-effects-in-human-acute-promyelocytic-leukemia-nb4-cells-via-autophagy
#19
Aila Fakhimahmadi, Farinaz Nazmi, Marveh Rahmati, Nazila Moghtaran Bonab, Mehrdad Hashemi, Mohammad Amin Moosavi
Here, we report that targeting Nucleostemin (NS), a recently discovered stem cells-enriched gene, by a specific small interference RNA (siNS), decreases the rate of proliferation of acute promyelocytic leukemia (APL) NB4 cells and induces differentiation and autophagy. In addition, NS silencing promotes the effects of all-trans-retinoic acid (ATRA)-based differentiation therapy in NB4 cells. Autophagy inhibitors 3-methyladenine and bafilomycin block the effect of NS targeting on differentiation, indicating a new functional link between NS and autophagy as an important regulator of differentiation in NB4 cells...
October 26, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29081694/recurrent-fusion-genes-in-leukemia-an-attractive-target-for-diagnosis-and-treatment
#20
REVIEW
Yuhui Wang, Nan Wu, Duo Liu, Yan Jin
INTRODUCTION: Since the first fusion gene was discovered decades ago, a considerable number of fusion genes have been detected in leukemia. The majority of them are generated through chromosomal rearrangement or abnormal transcription. With the development of techniques, high-throughput sequencing method makes it possible to detect fusion genes systematically in multiple human cancers. Owing to their biological significance and tumor-specific expression, some of the fusion genes are attractive diagnostic tools and therapeutic targets...
October 2017: Current Genomics
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