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Acute promyelocyte leukemia

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https://www.readbyqxmd.com/read/29326799/molecular-heterogeneity-in-acute-promyelocytic-leukemia-a-single-center-experience-from-india
#1
Nikhil Rabade, Goutham Raval, Shruti Chaudhary, P G Subramanian, Rohan Kodgule, Swapnali Joshi, Prashant Tembhare, Syed K Hasan, Hasmukh Jain, Manju Sengar, Gaurav Narula, Shripad Banavali, Pratibha Amare Kadam, Dhanalaxmi Shetty, Sumeet Gujral, Nikhil Patkar
Atypical breakpoints and variant APL cases involving alternative chromosomal aberrations are seen in a small subset of acute promyelocytic leukemia (APL) patients. Over seven different partner genes for RARA have been described. Although rare, these variants prove to be a diagnostic challenge and require a combination of advanced cytogenetic and molecular techniques for accurate characterization. Heterogeneity occurs not only at the molecular level but also at clinico-pathological level influencing treatment response and outcome...
2018: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/29301374/why-differentiation-therapy-sometimes-fails-molecular-mechanisms-of-resistance-to-retinoids
#2
REVIEW
Petr Chlapek, Viera Slavikova, Pavel Mazanek, Jaroslav Sterba, Renata Veselska
Retinoids represent a popular group of differentiation inducers that are successfully used in oncology for treatment of acute promyelocytic leukemia in adults and of neuroblastoma in children. The therapeutic potential of retinoids is based on their key role in the regulation of cell differentiation, growth, and apoptosis, which provides a basis for their use both in cancer therapy and chemoprevention. Nevertheless, patients treated with retinoids often exhibit or develop resistance to this therapy. Although resistance to retinoids is commonly categorized as either acquired or intrinsic, resistance as a single phenotypic feature is usually based on the same mechanisms that are closely related or combined in both of these types...
January 3, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29297235/l-ascorbic-acid-and-%C3%AE-tocopherol-attenuate-arsenic-trioxide-induced-toxicity-in-h9c2-cardiomyocytes-by-the-activation-of-nrf2-and-bcl2-transcription-factors
#3
Radhakrishnan Chandraprabha Vineetha, Prakash Binu, Pettamanna Arathi, Raveendran Harikumaran Nair
Arsenic trioxide (As2O3) is a potent drug for the treatment of acute promyelocytic leukemia (APL) and has achieved remarkable remissions in patients. Unfortunately, clinical reports have shown that the treatment is associated with cardiotoxicity. Many efforts have been made to mitigate drug mediated cardiac damage using naturally occurring antioxidant compounds possessing free radical scavenging activity. The present investigation aims to explore protective role of L-Ascorbic acid (L-AA) and α-Tocopherol (α-TOC) from As2O3 induced oxidative stress in H9c2 cardiomyocytes through the evaluation of Nrf2 (Nuclear factor erythroid 2-related factor 2) and Bcl-2 (B-cell lymphoma 2) transcription factors...
January 3, 2018: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/29296827/clinical-impact-of-baalc-expression-in-high-risk-acute-promyelocytic-leukemia
#4
Antonio R Lucena-Araujo, Diego A Pereira-Martins, Luisa C Koury, Pedro L Franca-Neto, Juan L Coelho-Silva, Virginia M de Deus Wagatsuma, Raul A M Melo, Rosane Bittencourt, Katia Pagnano, Ricardo Pasquini, Carlos S Chiattone, Evandro M Fagundes, Maria de Lourdes Chauffaille, Stanley L Schrier, Martin S Tallman, Raul C Ribeiro, David Grimwade, Arnold Ganser, Bob Löwenberg, Francesco Lo-Coco, Miguel A Sanz, Nancy Berliner, Eduardo M Rego
Although overexpression of the brain and acute leukemia, cytoplasmic (BAALC) gene is associated with primary resistant disease and shorter relapse-free, disease-free, and overall survival in different subsets of acute myeloid leukemia (AML), little is known about its clinical impact in acute promyelocytic leukemia (APL). Using real-time reverse transcriptase polymerase chain reaction, we showed that BAALC expression is significantly lower in APL compared with other subsets of AML (P < .001). We also demonstrated that BAALC overexpression was associated with shorter disease-free survival (DFS) (hazard ratio [HR], 4...
September 26, 2017: Blood Advances
https://www.readbyqxmd.com/read/29289982/difference-in-causes-and-prognostic-factors-of-early-death-between-cohorts-with-de-novo-and-relapsed-acute-promyelocytic-leukemia
#5
Hongli Zhao, Yanqiu Zhao, Yingmei Zhang, Jinxiao Hou, Huiyuan Yang, Fenglin Cao, Yiju Yang, Wenyi Hou, Jiayue Sun, Bo Jin, Jinyue Fu, Haitao Li, Ping Wang, Fei Ge, Jin Zhou
Early death (ED) remains the most critical issue in the current care of patients with acute promyelocytic leukemia (APL). Very limited data are available regarding ED in patients with relapsed APL. In this retrospective study, 285 de novo and 79 relapsed patients were included. All patients received single-agent arsenic trioxide as induction therapy. The differences in baseline clinical features, incidence, causes, and prognostic factors of ED were compared between the two patient cohorts. The relapse cohort exhibited a better overall condition than the de novo cohort upon hospital admission...
December 30, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/29288518/participation-of-delta-annexin-a3-in-the-ribosomal-protein-s19-c-terminus-dependent-inhibitory-mechanism-of-the-neutrophil-c5a-receptor-through-delta-lactoferrin
#6
Koji Yamanegi, Naoko Yamada, Keiji Nakasho, Hiroshi Nishiura
Although C5a receptor (C5aR) interacting with its agonist C5a promotes acute inflammation during the initiation phase, the roles of the recycling C5aR during the resolution phase are still unclear. We found that C5aR interacted with its antagonist/agonist ribosomal protein S19 (RP S19) polymer or a RP S19 polymer functional analogue S-tagged C5a/RP S19, which connects an RP S19 C-terminus (IAGQVAAANKKH) to the S-tagged C5a C-terminus, promoted acute inflammation at the resolution phase via an activation of the apoptosis-inducing transcription factor delta lactoferrin (δLf) in neutrophils and the membrane mobilizing factor full-length annexin A3 (ANXA3) in macrophages...
December 29, 2017: Pathology International
https://www.readbyqxmd.com/read/29286665/sodium-periodate-mediated-harringtonine-derivatives-and-their-antiproliferative-activity-against-hl-60-acute-leukemia-cells
#7
Seiichi Sakamoto, Tomofumi Miyamoto, Kazuteru Usui, Hiroyuki Tanaka, Satoshi Morimoto
Harringtonine (HT) is a naturally occurring alkaloid isolated from the plant genus Cephalotaxus. It possesses antileukemic activity and has been clinically utilized for the treatment of acute leukemia and lymphoma. Sodium periodate (NaIO4) was reacted with HT to produce five HT derivatives including four novel compounds. Their antiproliferative activity against HL-60 acute promyelocytic leukemia cells revealed that the presence of the C-5' methyl group enhances the antiproliferative activity because the IC50 values of the HT derivatives, including HT1 (5'-de-O-methylharringtonine), were at least 2000 times higher (>100 μM) than that of HT (∼47 nM)...
December 29, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/29274627/regulation-of-abcg2-by-nuclear-factor-kappa-b-affects-the-sensitivity-of-human-lung-adenocarcinoma-a549-cells-to-arsenic-trioxide
#8
Xuejun Jiang, Chengzhi Chen, Shiyan Gu, Zunzhen Zhang
Arsenic trioxide (As2O3) is successfully used as an anticancer agent against acute promyelocytic leukemia and some solid tumors. However, the application of As2O3 is largely limited by its drug resistance in the treatment of non-small cell lung carcinoma (NSCLC). Therefore, it is an urgent task to enhance the sensitivity of lung cancer cells to As2O3. In this study, using human lung adenocarcinoma A549 cells as a cell culture model, we demonstrated that an adenosine triphosphate binding cassette (ABC) transporter, ABCG2, was significantly increased by As2O3 treatment, while other ABC transporters, ABCB1 and ABCC1 showed no remarkable change in the response to As2O3...
December 17, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/29274134/a-distinct-immunophenotype-identifies-a-subset-of-npm1-mutated-aml-with-tet2-or-idh1-2-mutations-and-improved-outcome
#9
Emily F Mason, Frank C Kuo, Robert P Hasserjian, Adam C Seegmiller, Olga Pozdnyakova
Recent work has identified distinct molecular subgroups of acute myeloid leukemia (AML) with implications for disease classification and prognosis. NPM1 is one of the most common recurrently mutated genes in acute myeloid leukemia (AML). NPM1 mutations often co-occur with FLT3-ITDs and mutations in genes regulating DNA methylation, such as DNMT3A, TET2, and IDH1/2. It remains unclear whether these genetic alterations are associated with distinct immunophenotypic findings or affect prognosis. We identified 133 cases of NPM1-mutated AML and correlated sequencing data with immunophenotypic and clinical findings...
December 23, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/29251252/the-clinical-significance-of-flt3-itd-mutation-on-the-prognosis-of-adult-acute-promyelocytic-leukemia
#10
Yingchao Fan, Yanan Cao, Xiaosong Bai, Wenfang Zhuang
BACKGROUND AND AIMS: To explore the relationship between FLT3 (encoding Fms related tyrosine kinase 3) internal tandem duplication (ITD) mutations with the prognosis of acute promyelocytic leukemia. The PubMed database, the Cochrane Library, conference proceedings, the EMBASE databases, and references of published trials and review articles were searched. Two reviewers independently assessed the quality of the trials and extracted the data. Odd ratios (ORs) for complete remission (CR) rate after induction therapy, 5-year overall survival (OS), and 5-year disease free survival (DFS) were pooled using the STATA package...
December 18, 2017: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/29245895/progress-and-criticalities-in-the-management-of-acute-promyelocytic-leukemia
#11
EDITORIAL
Francesco Lo-Coco, Laura Cicconi, Maria Teresa Voso
No abstract text is available yet for this article.
November 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/29243797/rapamycin-induces-human-acute-promyelocytic-leukemia-cell-hl-60-autophagic-apoptosis
#12
Y-H Zhang, Q-F Lin, X-L Wang, Q-Y Li, J-J Chai, X-J Fan
OBJECTIVE: We aimed at investigating the effects of rapamycin on apoptosis and autophagy of human acute promyelocytic leukemia cell line HL-60, and to preliminarily explore the mechanism of extra medullary infiltration of leukemia cells with human acute promyelocytic leukemia cell line HL-60 as the object of study, providing a theoretical basis for the clinical treatment of leukemia. MATERIALS AND METHODS: After HL-60 cells were cultured in vitro, the effect of rapamycin on proliferation ability of HL-60 cells was determined by methyl thiazolyl tetrazolium (MTT) method, the cell apoptosis ratio was detected by flow cytometer, the change of autophagy after HL-60 cells acted by rapamycin was tested by monodansylcadaverine (MDC) fluorescence staining, the mRNA expression of autophagy-related molecule was detected by polymerase chain reaction (PCR), and the expressions of apoptosis-related protein and autophagy-related protein were determined by Western blotting (WB)...
December 2017: European Review for Medical and Pharmacological Sciences
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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)
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