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Acute promyelocytic leukemia

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https://www.readbyqxmd.com/read/29237593/identification-of-novel-recurrent-stat3-rara-fusions-in-acute-promyelocytic-leukemia-lacking-t-15-17-q22-q12-pml-rara
#1
Li Yao, Lijun Wen, Nana Wang, Tianhui Liu, Yang Xu, Changgeng Ruan, Depei Wu, Suning Chen
No abstract text is available yet for this article.
December 13, 2017: Blood
https://www.readbyqxmd.com/read/29232592/the-impact-of-oral-arsenic-and-all-trans-retinoic-acid-on-coagulopathy-in-acute-promyelocytic-leukemia
#2
Hong-Hu Zhu, Zhi-Ping Guo, Jin-Song Jia, Qian Jiang, Hao Jiang, Xiao-Jun Huang
The aim of our study was to evaluate the impact of oral arsenic (the realgar-indigo naturalis formula, RIF) and all-trans retinoic acid (ATRA) on coagulopathy in acute promyelocytic leukemia (APL) compared with intravenous arsenic trioxide (ATO) and ATRA during induction. Mitoxantrone was added to all the patients at a dose of 1.4mg/m2 per day for 5-7 days. D-dimer levels, prothrombin time (PT), fibrinogen (Fbg) levels and the platelet count were comparably analyzed among 83 newly diagnosed APL patients treated with RIF (n=45) or with ATO (n=38)...
November 15, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29228618/calcium-homeostasis-and-endoplasmic-reticulum-stress-are-involved-in-salvianolic-acid-b-offered-protection-against-cardiac-toxicity-of-arsenic-trioxide
#3
Jing-Yi Zhang, Bin Zhang, Min Wang, Wei Wang, Ping Liao, Gui-Bo Sun, Xiao-Bo Sun
Arsenic trioxide (ATO) is a potent anticancer agent used to treat acute promyelocytic leukemia. However, its cardiotoxicity limits ATO's widespread clinical use. Previous studies demonstrated that ATO may aggravate Ca2+ overload and promote endoplasmic reticulum stress (ERS). Salvianolic acid B (Sal B) is cardioprotective against ATO and enhances ATO's anticancer activities. The present study assessed whether the Sal B protective effect was related to maintenance of Ca2+ homeostasis and inhibition of ER stress...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29225170/dihydromyricetin-sensitizes-human-acute-myeloid-leukemia-cells-to-retinoic-acid-induced-myeloid-differentiation-by-activating-stat1
#4
Ming-Hui He, Qiang Zhang, Gang Shu, Ju-Chun Lin, Ling Zhao, Xiao-Xia Liang, Lizi Yin, Fei Shi, Hua-Lin Fu, Zhi-Xiang Yuan
The success of all-trans retinoic acid (ATRA) in differentiation therapy for patients with acute promyelocytic leukemia (APL) highly encourages researches to apply a new combination therapy based on ATRA. Therefore, research strategies to further sensitize cells to retinoids are urgently needed. In this study, we showed that Dihydromyricetin (DMY), a 2,3-dihydroflavonol compound, exhibited a strong synergy with ATRA to promote APL NB4 cell differentiation. We observed that DMY sensitized the NB4 cells to ATRA-induced cell growth inhibition, CD11b expression, NBT reduction and myeloid regulator expression...
December 7, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29224413/low-hox-gene-expression-in-pml-rar%C3%AE-positive-leukemia-results-from-suppressed-histone-demethylation
#5
Kateřina Rejlová, Alena Musilová, Karolina Škvárová Kramarzová, Markéta Žaliová, Karel Fišer, Meritxell Alberich-Jorda, Jan Trka, Júlia Starková
Homeobox (HOX) genes are frequently dysregulated in leukemia. Previous studies have shown that aberrant HOX gene expression accompanies leukemogenesis and affects disease progression and leukemia patient survival. Patients with acute myeloid leukemia (AML) bearing PML-RARα fusion gene has distinct HOX gene signature in comparison to other subtypes of AML patients although the mechanism of transcription regulation is not completely understood. We previously found an association between the mRNA levels of HOX genes and those of the histone demethylases JMJD3 and UTX in PML-RARα- positive leukemia patients...
December 11, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/29222233/current-management-of-philadelphia-chromosome-positive-all-and-the-role-of-stem-cell-transplantation
#6
REVIEW
Farhad Ravandi
Treatment of Philadelphia chromosome positive acute lymphoblastic leukemia exemplifies how the addition of potent targeted agents, directed at the molecular aberrations responsible for leukemic transformation, can overcome resistance mechanisms to traditional regimens and lead to improved outcomes. The introduction of BCR-ABL1 targeted tyrosine kinase inhibitors (TKIs) has significantly improved the outcomes not only by allowing more patients to undergo allogeneic hematopoietic cell transplantation (alloHCT) but also by decreasing our reliance on this potentially toxic strategy, particularly in the less fit population...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29214213/therapeutic-potential-of-arsenic-trioxide-ato-in-treatment-of-hepatocellular-carcinoma-role-of-oxidative-stress-in-ato-induced-apoptosis
#7
Erika B Dugo, Clement G Yedjou, Jacqueline J Stevens, Paul B Tchounwou
Hepatocellular carcinoma (HCC), the dominant form of primary liver cancer, is the sixth most common cancer in the world with more than 700,000 people diagnosed annually. Arsenic trioxide (ATO) has been shown to be a potent anticancer agent in various carcinomas, proving particularly effective in the clinical treatment of relapsed and refractory acute promyelocytic leukemia. However, its bioactivity and molecular mechanisms against HCC has not been fully studied. Using human HCC (HepG2) cells as a test model, we studied the effects of ATO and examined the role of oxidative stress (OS) and apoptosis in cytotoxicity...
2017: Annals of Clinical Pathology
https://www.readbyqxmd.com/read/29212418/clinical-characteristics-and-outcome-of-childhood-acute-promyelocitic-leukemia-apl-in-saudi-arabia-a-multicenter-saphos-leukemia-group-study
#8
Wasil Jastaniah, Abdulrahman Alsultan, Saad Al Daama, Walid Ballourah, Mohamed Bayoumy, Faisal Al-Anzi, Omar Al Shareef, Mohammed Burhan Abrar, Reem Al Sudairy, Ibrahim Al Ghemlas
BACKGROUND: Acute promyelocytic leukemia (APL) is a rare form of acute myelogenous leukemia (AML). Survival rates exceed 80% in developed countries. Successful treatments rely on all-trans retinoic acid with anthracycline-based chemotherapy. Availability of modern care and public knowledge play important roles in pediatric APL survival. METHOD: A cytogenetic diagnosis of APL was confirmed in 30 (14.5%) out of 207 children consecutively diagnosed with de novo AML between January 2005 and December 2012 at nine cancer care centers in Saudi Arabia...
December 7, 2017: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/29207612/the-antitumor-effect-of-arsenic-trioxide-on-hepatocellular-carcinoma-is-enhanced-by-andrographolide
#9
Xuhua Duan, Tengfei Li, Xinwei Han, Jianzhuang Ren, Pengfei Chen, Hao Li, Shaojun Gong
High concentrations of arsenic trioxide (As2O3) are used to treat acute promyelocytic leukemia and solid tumors, with negative side effects to normal cells. Andrographolide is a traditional Chinese medicine that exerts anti-cancer, anti-inflammatory, anti-virus, and anti-diabetic effects. Here, we tested the effects of combined andrographolide with As2O3 against hepatocellular carcinoma (HCC). We found that by increasing apoptosis, andrographolide synergistically enhanced the anti-tumor effects of As2O3 in HepG2 cells in vitro and in vivo...
October 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/29200694/pancreatitis-in-acute-promyelocytic-leukemia-drug-induced-or-differentiation-syndrome
#10
Dibyendu De, Uttam Kumar Nath, Prantar Chakrabarti
Acute promyelocytic leukemia (APL) constitutes about 15% of all acute myeloid leukemia patients and can now be treated even without any chemotherapy, with all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO). Acute pancreatitis (AP) is a rare adverse event in APL, which is primarily reported to be secondary to hypertriglyceridemia. Here, we have reported AP developed in a patient of APL, during induction with ATRA and ATO, but it was not associated with hypertriglyceridemia. Rather, it was associated with respiratory distress and weight gain, coincidental leukocytosis, bilateral pleural effusion, and edematous pancreatitis without any necrosis...
July 2017: Indian Journal of Medical and Paediatric Oncology
https://www.readbyqxmd.com/read/29193405/epigallocatechin-3-gallate-enhances-differentiation-of-acute-promyelocytic-leukemia-cells-via-inhibition-of-pml-rar%C3%AE-and-hdac1
#11
Maliheh Moradzadeh, Abazar Roustazadeh, Alijan Tabarraei, Saiedeh Erfanian, Amirhossein Sahebkar
The use of all-trans retinoic acid (ATRA) has dramatically improved the treatment and survival rate of patients with acute promyelocytic leukemia (APL). However, toxicity and resistance to this drug are major problems in the treatment of APL with ATRA. Earlier studies have suggested that the green tea polyphenol epigallocatechin gallate (EGCG) induces cell death in hematopoietic neoplasms without adversely affecting normal cells. In the present study, the potential therapeutic effect of EGCG in APL and the underlying molecular mechanisms were investigated...
November 29, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/29191918/pml-nuclear-body-disruption-cooperates-in-apl-pathogenesis-and-impairs-dna-damage-repair-pathways-in-mice
#12
Edwige Voisset, Eva Moravcsik, Eva W Stratford, Amie Jaye, Christopher J Palgrave, Robert K Hills, Paolo Salomoni, Scott C Kogan, Ellen Solomon, David Grimwade
A hallmark of acute promyelocytic leukemia (APL) is altered nuclear architecture, with disruption of PML nuclear bodies (NBs) mediated by the PML-RARα oncoprotein. To address whether this phenomenon plays a role in disease pathogenesis, we generated a knock-in mouse model with NB disruption mediated by two point mutations (C62A/C65A) in the Pml RING domain. While no leukemias developed in PmlC62A/C65A mice, these transgenic mice also expressing RARα linked to a dimerization domain (p50-RARα model) exhibited a doubling in the rate of leukemia, with a reduced latency period...
November 30, 2017: Blood
https://www.readbyqxmd.com/read/29166740/-factors-associated-with-early-treatment-response-in-adults-with-acute-myeloid-leukemia
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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