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Acute promyelocyte leukemia

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https://www.readbyqxmd.com/read/28743050/pml-rar%C3%AE-stabilized-by-zinc-in-human-acute-promyelocytic-leukemia-nb4-cells
#1
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
#2
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
#3
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
#4
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
#5
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
https://www.readbyqxmd.com/read/28717734/arsenic-as-traditional-chinese-medicine-provides-new-hope-for-overcoming-high-treatment-costs-of-acute-promyelocytic-leukemia
#6
Hong-Hu Zhu, Jiong Hu, Xue-Fei Gu
No abstract text is available yet for this article.
December 2016: Journal of Global Oncology
https://www.readbyqxmd.com/read/28716444/thiosemicarbazone-derivatives-thiazolyl-hydrazones-effectively-inhibit-leukemic-tumor-cell-growth-down-regulation-of-ribonucleotide-reductase-activity-and-synergism-with-arabinofuranosylcytosine
#7
Geraldine Graser-Loescher, Agnes Schoenhuber, Caroline Ciglenec, Sabine Eberl, Georg Krupitza, Robert M Mader, Surender Singh Jadav, Venkatesan Jayaprakash, Monika Fritzer-Szekeres, Thomas Szekeres, Philipp Saiko
Cellular growth inhibition exerted by thiosemicarbazones is mainly attributed to down-regulation of ribonucleotide reductase (RNR) activity, with RNR being responsible for the rate-limiting step of de novo DNA synthesis. In this study, we investigated the antineoplastic effects of three newly synthesized thiosemicarbazone derivatives, thiazolyl hydrazones, in human HL-60 promyelocytic leukemia cells. The cytotoxicity of compounds alone and in combination with arabinofuranosylcytosine (AraC) was determined by growth inhibition assays...
July 14, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28713949/shikonin-suppresses-proliferation-and-induces-apoptosis-in-human-leukemia-nb4-cells-through-modulation-of-mapks-and-c%C3%A2-myc
#8
Zhi-Ling Shan, Liang Zhong, Chu-Lan Xiao, Liu-Gen Gan, Ting Xu, Hao Song, Rong Yang, Liu Li, Bei-Zhong Liu
Acute promyelocytic leukemia (APL) is a special subtype of acute myeloid leukemia that responds to treatment with all‑trans retinoic acid and arsenic trioxide. However, severe side effects and drug resistance limit the effectiveness of these treatments. Hence, new drugs for APL are required urgently. Shikonin, an active naphthoquinone derived from the Chinese medical herb Zi Cao exerts antitumor activity in several cancers. In the present study, the effects of shikonin on proliferation and apoptosis in NB4 cells, as well as related mechanisms were assessed...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28712407/-detection-and-clinical-significance-of-pml-protein-expression-of-acute-promyelocytic-leukemia-cells
#9
Mei Song, Xiumei Wu, Mei Zhang, Pengcheng He
Objective To study the expression patterns of promyelocytic leukemia (PML) protein at different stages of acute promyelocytic leukemia (APL) and investigate the effects that the arsenical, all-trans retinoic acid (ATRA) and chemotherapeutic drugs on PML protein expression patterns. Methods The bone marrow cells of 42 APL patients, NB4 cells and MR2 cells were collected and treated separately with 1 μmol/L arsenic trioxide (As2O3), 1 μmol/L tetra-arsenic tetra-sulfide (As4S4), 1 μmol/L ATRA, 10 mg/L cytosine arabinoside, and 1 mg/L homoharringtonine...
July 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28711674/hplc-hg-afs-determination-of-arsenic-species-in-acute-promyelocytic-leukemia-apl-plasma-and-blood-cells
#10
Meihua Guo, Wenjing Wang, Xin Hai, Jin Zhou
Arsenic trioxide (ATO) has been successfully used in the treatment of acute promyelocytic leukemia (APL). To clarify the arsenic species in APL patients, high performance liquid chromatography-hydride generation-atomic fluorescence spectrometry (HPLC-HG-AFS) and HG-AFS methods were developed and validated to quantify the plasma concentrations of inorganic arsenic (As(III) and As(V)) and methylated metabolites (MMA and DMA), and the total amounts of arsenic in blood cells and plasma. Blood cells and plasma were digested with mixtures of HNO3H2O2 and analyzed by HG-AFS...
July 6, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28709826/synthesis-antioxidant-and-antiproliferative-activities-of-1-3-4-thiadiazoles-derived-from-phenolic-acids
#11
Katarina Jakovljević, Ivana Z Matić, Tatjana Stanojković, Ana Krivokuća, Violeta Marković, Milan D Joksović, Nevena Mihailović, Marija Nićiforović, Ljubinka Joksović
Two 2-amino-1,3,4-thiadiazoles containing phenolic hydroxyl groups were combined with different carboxylic acid chlorides giving sixteen amide derivatives with good antioxidant and antiproliferative potential. The compound 3'c with an adamantane ring displayed excellent DPPH radical scavenging activity and good cytotoxic activity against human acute promyelocytic leukemia HL-60 cells, while 1,3,4-thiadiazole 3'h with 4-chlorophenyl moiety was found to be the most effective in inhibition of survival of lung carcinoma A549 cells...
July 3, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28706392/acquired-aplastic-anemia-associated-with-trisomy-eight-converting-into-acute-myeloid-leukemia
#12
Sumit Grover, Amit Kumar Dhiman, Bhavna Garg, Neena Sood, Vikram Narang
Aplastic anemia (AA) is nowadays considered to be a clonal disorder arising from a defective hematopoietic stem cell developing after a generalized insult to bone marrow. Immunosuppressive treatment (IST) of AA causes suppression of the target dominant population of haematopoietic cells allowing the defective non targeted clones to expand. This may give rise to acute leukemia. Cytogenetic studies for chromosomal aberrations such as trisomy and monosomy may help in detecting such conversions. We present a case of acquired AA in a 60-year-old male presenting with pancytopenia and hypoplastic marrow treated with antithymocyte globulin, converting into myelodysplastic syndrome and later on acute promyelocytic leukemia after being in remission for 4 years...
July 2017: Journal of Laboratory Physicians
https://www.readbyqxmd.com/read/28705776/short-and-medium-term-biological-variation-estimates-of-leukocytes-extended-to-differential-count-and-morphology-structural-parameters-cell-population-data-in-blood-samples-obtained-from-healthy-people
#13
Sabrina Buoro, Anna Carobene, Michela Seghezzi, Barbara Manenti, Aurelio Pacioni, Ferruccio Ceriotti, Cosimo Ottomano, Giuseppe Lippi
BACKGROUND: Recent studies showed that some cell population data (CPD) parameters of neutrophils may be useful for diagnosing myelodysplastic syndromes and sepsis, for the differential diagnosis of acute promyelocytic leukemia, and some CPD parameters of lymphocytes may be a valuable tool for preliminary screening of B cell lymphoproliferative disease. Notwithstanding the knowledge, no information has been made available about their analytical quality specification. This study was aimed to define short- and medium-term biological variation (BV) estimates and reference change value (RCV) of leukocyte count, extended leukocyte differential and CPD...
July 10, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/28699720/in-vitro-cytotoxic-activity-evaluation-of-phenytoin-derivatives-against-human-leukemia-cells
#14
Katarzyna Śladowska, Jadwiga Handzlik, Katarzyna Kieć-Kononowicz, Lidia Mazur
Hydantoin derivatives, including phenytoin (5,5-diphenylhydantoin), have recently gained attention as they possess a variety of important biochemical and pharmacological properties. Nevertheless, available information on anticancer activity of hydantoin derivatives is still scarce. Here, we evaluated possible antileukemic potential of four phenytoin analogs, namely: methyl 2-(2,4-dioxo-5,5-diphenylimidazolidin-3-yl)propanoate (1), methyl 2-(1-(3-bromopropyl)-2,4-dioxo-5,5-diphenylimidazolidin-3-yl)propanoate (2), 1-(3-bromopropyl)-3-methyl-5,5-diphenylimidazolidine-2,4-dione (3) and 1-(3-bromobutyl)-3-methyl-5,5-diphenylimidazolidine-2,4-dione (4)...
September 2016: Indian Journal of Experimental Biology
https://www.readbyqxmd.com/read/28694043/risk-factors-and-clinical-characteristics-of-non-promyelocytic-acute-myeloid-leukemia-of-intracerebral-hemorrhage-a-single-center-study-in-china
#15
Qiaolei Zhang, Xueying Li, Zhangyue Wei, Xiujin Ye, Lixia Zhu, Mixue Xie, Wanzhuo Xie, Jingjing Zhu, Li Li, De Zhou, Yanlong Zheng, Xiudi Yang, Mingyu Zhu, Jianai Sun
BACKGROUND: Although high mortality in patients with acute leukemia (AL) is associated with intracranial hemorrhage (ICH), the clinical features and pathogenesis of AL patients with cerebral hemorrhage are not well known. METHODS: We diagnosed 90 patients with ICH from a total of 1467 patients with non-promyelocytic AL who had been hospitalized in the First Affiliated Hospital of Medical School of Zhejiang University from January 2010 to October 2015. Moreover, the risk factors of ICH death were evaluated...
July 7, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/28687976/annexin-a2-s100a10-heterotetramer-is-upregulated-by-pml-rar%C3%AE-fusion-protein-and-promotes-plasminogen-dependent-fibrinolysis-and-matrix-invasion-in-acute-promyelocytic-leukemia
#16
Dan Huang, Yan Yang, Jian Sun, Xiaorong Dong, Jiao Wang, Hongchen Liu, Chengquan Lu, Xueyu Chen, Jing Shao, Jinsong Yan
Aberrant expression of annexin A2-S100A10 heterotetramer (AIIt) associated with PML/RARα fusion protein causes lethal hyperfibrinolysis in acute promyelocytic leukemia (APL), but the mechanism is unclear. To facilitate the investigation of regulatory association between ANXA2 and promyelocytic leukemia/retinoic acid receptor α (PML/RARα) fusion protein, this work was performed to determine the transcription start site of ANXA2 promoter with rapid amplification of 5'-cDNA ends analysis. Zinc-induced U937/PR9 cells expressed PML/RARα fusion protein, and resultant increases in ANXA2 transcripts and translational expressions of both ANXA2 and S100A10, while S100A10 transcripts remained constitutive...
July 8, 2017: Frontiers of Medicine
https://www.readbyqxmd.com/read/28686804/smart-human-serum-albumin-as2o3-nanodrug-with-self-amplified-folate-receptor-targeting-ability-for-chronic-myeloid-leukemia-treatment
#17
Yongbo Peng, Zilong Zhao, Teng Liu, Xiong Li, Xiaoxiao Hu, Xiaoping Wei, Xiaobing Zhang, Weihong Tan
Arsenic trioxide (ATO, As2O3) is currently used to treat acute promyelocytic leukemia. However, expanding its use to include high-dose treatment of other cancers is severely hampered by serious side effects on healthy organs. To address these limitations, we loaded ATO onto folate (FA)-labeled human serum albumin (HSA) pretreated with glutathione (GSH) based on the low pH- and GSH-sensitive arsenic-sulfur bond, and we termed the resulting smart nanodrug as FA-HSA-ATO. FA-HSA-ATO could specifically recognize folate receptor-β-positive chronic myeloid leukemia (CML) cells, resulting in more intracellular accumulation of ATO...
July 7, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28685606/second-primary-malignancy-in-acute-promyelocytic-leukemia-a-surveillance-epidemiology-and-end-results-database-study
#18
Smith Giri, Ranjan Pathak, Madan Raj Aryal, Paras Karmacharya, Vijaya Raj Bhatt
No abstract text is available yet for this article.
July 7, 2017: Future Oncology
https://www.readbyqxmd.com/read/28685056/pml-silencing-inhibits-cell-proliferation-and-induces-dna-damage-in-cultured-ovarian-cancer-cells
#19
Sheng-Bing Liu, Zhong-Fei Shen, Yan-Jun Guo, Li-Xian Cao, Ying Xu
The promyelocytic leukemia (PML) gene is a tumor suppressor gene. It was first identified in acute promyelocytic leukemia, in which it is fused to retinoic acid receptor α by the (15;17) chromosomal translocation. The function of the PML protein is frequently lost or aberrant in human solid tumors. In human ovarian carcinoma tissue, PML detected by immunohistochemistry was highly expressed. A PML-silencing vector, pSRG-shPml, was constructed and used to transfect human ovarian cancer cells. Cells were cultured and selected with puromycin for 10-15 days, and then the PML mRNA expression levels were detected by RT-qPCR and immunofluorescence...
July 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28684780/retinoic-acid-affects-lung-adenocarcinoma-growth-by-inducing-differentiation-via-gata6-activation-and-egfr-and-wnt-inhibition
#20
Giovanni Zito, Flores Naselli, Laura Saieva, Stefania Raimondo, Giovanna Calabrese, Claudio Guzzardo, Stefano Forte, Christian Rolfo, Rosalba Parenti, Riccardo Alessandro
A fundamental task in cancer research aims at the identification of new pharmacological therapies that can affect tumor growth. Differentiation therapy might exploit this function not only for hematological diseases, such as acute promyelocytic leukemia (APML) but also for epithelial tumors, including lung cancer. Here we show that Retinoic Acid (RA) arrests in vitro and in vivo the growth of Tyrosine Kinase Inhibitors (TKI) resistant Non Small Cell Lung Cancer (NSCLC). In particular, we found that RA induces G0/G1 cell cycle arrest in TKI resistant NSCLC cells and activates terminal differentiation programs by modulating the expression of GATA6, a key transcription factor involved in the physiological differentiation of the distal lung...
July 6, 2017: Scientific Reports
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