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Acute leukemias

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https://www.readbyqxmd.com/read/29346763/derepression-of-the-iroquois-homeodomain-transcription-factor-gene-irx3-confers-differentiation-block-in-acute-leukemia
#1
Tim D D Somerville, Fabrizio Simeoni, John A Chadwick, Emma L Williams, Gary J Spencer, Katalin Boros, Christopher Wirth, Eleni Tholouli, Richard J Byers, Tim C P Somervaille
The Iroquois homeodomain transcription factor gene IRX3 is expressed in the developing nervous system, limb buds, and heart, and transcript levels specify obesity risk in humans. We now report a functional role for IRX3 in human acute leukemia. Although transcript levels are very low in normal human bone marrow cells, high IRX3 expression is found in ∼30% of patients with acute myeloid leukemia (AML), ∼50% with T-acute lymphoblastic leukemia, and ∼20% with B-acute lymphoblastic leukemia, frequently in association with high-level HOXA gene expression...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29346508/oroxylin-a%C3%AF-a-natural-compound-mitigates-the-negative-effects-of-tnf%C3%AE-treated-acute-myelogenous-leukemia-cells
#2
Hui Li, Na Lu, Xiaoxuan Yu, Xiao Liu, Po Hu, Yu Zhu, Le Shen, Jingyan Xu, Zhiyu Li, Qinglong Guo, Hui Hui
Tumor necrosis factor alpha (TNFα) is a complicated cytokine which is involved in proliferation and differentiation of acute myelogenous leukemia (AML) cells through a poorly understood mechanism. Mechanistic studies indicate that TNFα induced binding of PI3K subunit p85α to N-terminal truncated nuclear receptor RXRα (tRXRα) proteins, and activated AKT. The activated PI3K/AKT pathway negatively regulated differentiation of AML cells through the up-regulation of c-Myc. In addition, TNFα also induced activation of nuclear factor κB (NF-κB), a nuclear transcription factor which was shown to promote cell proliferation...
January 13, 2018: Carcinogenesis
https://www.readbyqxmd.com/read/29346478/differentiation-syndrome-associated-with-enasidenib-a-selective-inhibitor-of-mutant-isocitrate-dehydrogenase-2-analysis-of-a-phase-1-2-study
#3
Amir T Fathi, Courtney D DiNardo, Irina Kline, Laurie Kenvin, Ira Gupta, Eyal C Attar, Eytan M Stein, Stephane de Botton
Importance: Enasidenib mesylate, a mutant isocitrate dehydrogenase 2 (IDH2) protein inhibitor that promotes differentiation of leukemic myeloblasts, was recently approved by the US Food and Drug Administration for use in relapsed/refractory (R/R) mutant IDH2 acute myeloid leukemia (AML). During the first study of enasidenib in humans, a minority of patients with advanced myeloid neoplasms experienced unexpected signs/symptoms of a differentiation syndrome (DS), a potentially lethal entity...
January 18, 2018: JAMA Oncology
https://www.readbyqxmd.com/read/29346477/enasidenib-induced-differentiation-syndrome-in-idh2-mutant-acute-myeloid-leukemia
#4
Shyam A Patel
No abstract text is available yet for this article.
January 18, 2018: JAMA Oncology
https://www.readbyqxmd.com/read/29345570/the-role-of-ampk-mtor-modulators-in-therapy-of-acute-myeloid-leukemia
#5
Dora Visnjic, Vilma Dembitz, Hrvoje Lalic
Differentiation therapy of acute promyelocytic leukemia with all-trans retinoic acid represents the most successful pharmacological therapy of acute myeloid leukemia (AML). Numerous studies demonstrate that drugs that inhibit mechanistic target of rapamycin (mTOR) and activate AMP-kinase (AMPK) have beneficial effects in promoting differentiation and blocking proliferation of AML. Most of these drugs are already in use for other purposes; rapalogs as immunosuppressants, biguanides as oral antidiabetics, and 5-amino-4-imidazolecarboxamide ribonucleoside (AICAr, acadesine) as an exercise mimetic...
January 16, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29345422/cantharidic-acid-induces-apoptosis-of-human-leukemic-hl-60-cells-via-c-jun-n-terminal-kinase-regulated-caspase-8-9-3-activation-pathway
#6
Shih-Chung Wang, Jyh-Ming Chow, Ming-Hsien Chien, Chiao-Wen Lin, Hui-Yu Chen, Pei-Ching Hsiao, Shun-Fa Yang
Cantharidin, a natural toxin from blister beetles, has shown potent anticancer activities on many solid tumor cells. Recently, cantharidin and its analogue, norcantharidin, were also shown to suppress nonsolid tumors such as chronic myeloid leukemia, acute myeloid leukemia (AML), and leukemic stem cells. However, there is no available information to address the effects of cantharidic acid (CAC), a hydrolysis product of cantharidin, on human AML cells. The present study showed that CAC, at a range of concentrations (0-20 μM), concentration-dependently inhibited cell proliferation in the HL-60 AML cell line...
January 18, 2018: Environmental Toxicology
https://www.readbyqxmd.com/read/29345177/prognostic-significance-of-cathepsin-l-expression-in-pediatric-acute-myeloid-leukemia
#7
Garima Pandey, Sameer Bakhshi, Bhaskar Thakur, Prerna Jain, Shyam S Chauhan
Overexpression of cathepsin L (CTSL), an endolysosomal cysteine protease, is associated with inferior survival of patients with various human malignancies. We evaluated the expression/activity of CTSL in peripheral blood mononuclear cells (PBMCs) and bone marrow mononuclear cells (BMMCs) of 103 pediatric acute myeloid leukemia (AML) patients to assess its prognostic significance in this malignancy. Thirty-five healthy siblings of patients served as controls. Our results revealed significantly higher CTSL activity (p < ...
January 18, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29345176/bone-marrow-vegfc-expression-is-associated-with-multilineage-dysplasia-and-several-prognostic-markers-in-adult-acute-myeloid-leukemia-but-not-with-survival
#8
Vicent Guillem, Marisa Calabuig, Salut Brunet, Jordi Esteve, Lourdes Escoda, David Gallardo, Josep-Maria Ribera, María Paz Queipo de Llano, Montserrat Arnan, Carme Pedro, María Luz Amigo, Josep M Martí-Tutusaus, Antoni García-Guiñón, Joan Bargay, Antonia Sampol, Olga Salamero, Llorenç Font, Carme Talarn, Montserrat Hoyos, Marina Díaz-Beyá, Ana Garrido, Blanca Navarro, Josep Nomdédeu, Jordi Sierra, Mar Tormo
Vascular endothelial growth factor C (VEGFC) stimulates leukemia cell proliferation and survival, and promotes angiogenesis. We studied VEGFC expression in bone marrow samples from 353 adult acute myeloid leukemia (AML) patients and its relationship with several clinical, cytogenetic, and molecular variables. We also studied the expression of 84 genes involved in VEGF signaling in 24 patients. We found that VEGFC expression was higher in AML patients with myelodysplasia-related changes (AML-MRC) than in patients with non-AML-MRC...
January 18, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29345172/real-world-data-on-first-relapse-of-acute-lymphoblastic-leukemia-in-patients-55-years
#9
Emma Bergfelt Lennmyr, Piotr Kozlowski, Lucia Ahlberg, Per Bernell, Erik Hulegårdh, Antonio Santamaria Izarra, Karin Karlsson, Beata Tomaszewska-Toporska, Maria Åström, Helene Hallböök
No abstract text is available yet for this article.
January 18, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29344636/analysis-of-the-prolonged-infusion-of-dfp-10917-a-deoxycytidine-analog-as-a-therapeutic-strategy-for-the-treatment-of-human-tumor-xenografts-in-vivo
#10
Kenzo Iizuka, Chun Zhang, Kokoro Eshima, Cheng Jin, Kiyoshi Eshima, Masakazu Fukushima
2'-C-cyano-2'-deoxy-1-β-D-arabino-pentofranocyl-cytosine (DFP-10917, CNDAC) is a 2'-deoxycytidine analog with antitumor activity against various tumor cells. However, a clinically available therapeutic regimen for this compound needs to be established and its functional mechanisms in relation to the dosing schedule need to be clarified. In this study, we evaluated the antitumor activity and toxicity of DFP-10917 by varying the dose and administration schedule in human solid tumor and leukemia xenografts in vivo...
January 16, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29344251/mir-218-inhibits-acute-promyelocytic-leukemia-cell-growth-by-targeting-bmi-1
#11
Yan Wang, Hai-Hong Sun, Ming-Hua Sui, Jun-Jie Ma
Acute promyelocytic leukemia (APL) is a subtype of acute myelocytic leukemia. Previous studies have reported a number of functions and therapeutic roles of microRNAs (miRs) in APL, and have suggested that miR-218 acts as a tumor suppressor in a number of types of human cancer; however, its role in APL remains unclear. In the present study, the expression of miR-218 and its effects on the viability and proliferation of HL-60 cells was investigated. Reverse transcription-quantitative polymerase chain reaction analysis demonstrated that miR-218 was frequently downregulated in APL marrow tissues compared with normal marrow tissues...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29344207/novel-homobarringtonie-containing-therapy-for-the-treatment-of-patients-with-primary-acute-myeloid-leukemia-that-are-resistant-to-conventional-therapy
#12
Jingsong He, Li Li, Jingjing Zhu, Weiyan Zheng, Wenjun Wu, Yanlong Zheng, Xiujin Ye
The current study investigated the efficacy and safety of a novel treatment regime consisting of homobarringtonie, cytosine arabinoside and etoposide (HCE) for the treatment of primary acute myeloid leukemia (AML). In the present study, 141 patients diagnosed with AML were divided into the HCE (n=47) and the conventional AML therapy, consisting of idamycin combined with cytarabine (IA; n=94), treatment groups. The measured patient outcome parameters were the emission and response rates, as well as medication-induced adverse events, with a median follow-up time of 28 months...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29344183/a-patient-with-chronic-myeloid-leukemia-and-situs-inversus-totalis-a-case-report
#13
Yunxia Sun, Xiaoli Li, Lijun Li, Huan Liu, Qian Xu, Bei Liu
In the present study, a case of chronic myeloid leukemia (CML) with complete situs inversus in a 68-year-old female patient was reported. The patient presented with general weakness, abdominal distension and tenderness in the right hypochondrium. A chest X-ray revealed a right-sided heart. Ultrasonography revealed situs inversus totalis. A bone marrow smear demonstrated CML in the accelerated phase. Imatinib mesylate was subsequently administered; the patient stopped taking imatinib mesylate following discharge from the hospital...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29344139/nls-rar%C3%AE-is-a-novel-transcriptional-factor
#14
Kai-Ling Jiang, Liang Zhong, Xiao-Qun Yang, Peng-Peng Ma, Hui Wang, Xin-Yu Zhu, Bei-Zhong Liu
Acute promyelocytic leukemia (APL) is characterized by the presence of the promyelocytic leukemia (PML)-retinoic acid receptor-α (RAR-α) fusion protein. PML-RARα can be cleaved by neutrophil elastase (NE) in several positions in cells in the promyelocytic stage, nuclear location signal (NLS)-negative PML and NLS-RARα may be the products of PML-RARα by NE. The function of NLS-RARα may be affected by the addition of NLS, which would alter its localization in cells, as the role of NLS is to identify proteins for transport to the nucleus...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29344132/aberrant-nlrp3-inflammasome-associated-with-aryl-hydrocarbon-receptor-potentially-contributes-to-the-imbalance-of-t-helper-cells-in-patients-with-acute-myeloid-leukemia
#15
Yan Jia, Chen Zhang, Mingqiang Hua, Min Wang, Ping Chen, Daoxin Ma
Acute myeloid leukemia (AML) is a hematological malignancy in which the immune response serves a pivotal role in progression. Aryl hydrocarbon receptor (AHR) is involved in the modulation of the immune system, particularly in the differentiation of T-helper cell (Th) subsets. Although the NLR family pyrin domain-containing 3 (NLRP3) inflammasome has been implicated as essential in the pathogenesis of autoimmune and inflammatory diseases, the role it serves in the development of AML remains unknown. Therefore, in order to identify and describe the possible roles of AHR, as well as NLRP3 inflammasome, in the pathogenesis of AML and their relationship with Th subsets (Th1 Th22), the present study investigated the mRNA expression levels of AHR and NLRP3 inflammasome molecules in the peripheral blood and bone marrow...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29344131/a-novel-variant-translocation-1-9-p22-q34-resulting-in-a-dek-nup214-fusion-gene-in-a-patient-with-acute-myeloid-leukemia-a-case-report
#16
Qishan Hao, Qi Zhang, Chengwen Li, Shuning Wei, Qinghua Li, Yang Song, Yingchang Mi
The present case report describes a 46-year-old female patient diagnosed with M4 acute myeloid leukemia (AML), accompanied with a t(1;9)(p22;q34) chromosomal abnormality. Transcriptome sequencing identified a DEK proto-oncogene (DEK)/nucleoporin (NUP)214 fusion gene, which results from the t(6;9)(p23;q34) chromosomal translocation. Polymerase chain reaction analysis and fluorescence in situ hybridization were used to verify the existence of the DEK/NUP214 fusion gene. Few patients with AML with the t(6;9)(p23;q34) chromosomal translocation have been reported to have other chromosomal or karyotype changes...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29344112/zgdhu-1-for-cancer-therapy
#17
Jinlin Liu, Liannv Qiu, Jun Xia, Sufeng Chen, Xiping Yu, Yonglie Zhou
N,N'-di-(m-methylphenyl)-3,6-dimethyl-1,4-dihydro-1,2,4,5-tetrazine-1,4-dicarboamide (ZGDHu-1) is a novel tetrazine derivative that was initially designed and produced by Professor W.X. Hu, and which has been reported by our group to exhibit antitumor activity. Accumulating evidence suggests that the anticancer mechanisms of ZGDHu-1 may be involved indifferent biological activities, particularly in acute myeloid leukemia (AML) cells. At a high concentration, ZGDHu-1 has been demonstrated to inhibit the proliferation of the leukemia cells by arresting the cell cycle at the G2/M phase, and by inducing cell apoptosis via inducing the accumulation of reactive oxygen species, the translocation of phosphatidylserine across the plasma membrane and the loss of mitochondrial membrane potential...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29344090/overexpression-of-the-proneural-transcription-factor-ascl1-in-chronic-lymphocytic-leukemia-with-a-t-12-14-q23-2-q32-3
#18
Theodora Malli, Melanie Rammer, Sabrina Haslinger, Jonathan Burghofer, Sonja Burgstaller, Hans-Christian Boesmueller, Renate Marschon, Wolfgang Kranewitter, Martin Erdel, Sabine Deutschbauer, Gerald Webersinke
Background: Translocations of the IGH locus on 14q32.3 are present in about 8% of patients with chronic lymphocytic leukemia (CLL) and contribute to leukemogenesis by deregulating the expression of the IGH-partner genes. Identification of these genes and investigation of the downstream effects of their deregulation can reveal disease-causing mechanisms. Case presentation: We report on the molecular characterization of a novel t(12;14)(q23.2;q32.3) in CLL. As a consequence of the rearrangement ASCL1 was brought into proximity of the IGHJ-Cμ enhancer and was highly overexpressed in the aberrant B-cells of the patient, as shown by qPCR and immunohistochemistry...
2018: Molecular Cytogenetics
https://www.readbyqxmd.com/read/29343975/spotlight-on-midostaurin-in-the-treatment-of-flt3-mutated-acute-myeloid-leukemia-and-systemic-mastocytosis-design-development-and-potential-place-in-therapy
#19
REVIEW
Ellen Weisberg, Martin Sattler, Paul W Manley, James D Griffin
The Fms-like tyrosine kinase-3 (FLT3; fetal liver kinase-2; human stem cell tyrosine kinase-1; CD135) is a class III receptor tyrosine kinase that is normally involved in regulating the proliferation, differentiation, and survival of both hematopoietic cells and dendritic cells. Mutations leading it to be constitutively activated make it an oncogenic driver in ~30% of acute myeloid leukemia (AML) patients where it is associated with poor prognosis. The prevalence of oncogenic FLT3 and the dependency on its constitutively activated kinase activity for leukemia growth make this protein an attractive target for therapeutic intervention...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29343974/identification-of-key-pathways-and-genes-in-tp53-mutation-acute-myeloid-leukemia-evidence-from-bioinformatics-analysis
#20
Rui Huang, Xiwen Liao, Qiaochuan Li
Background: Tumor protein p53 (TP53) mutations are not only a risk factor in acute myeloid leukemia (AML) but also a potential biomarker for individualized treatment options. This study aimed to investigate potential pathways and genes associated with TP53 mutations in adult de novo AML. Methods: An RNA sequencing dataset of adult de novo AML was downloaded from The Cancer Genome Atlas database. Differentially expressed genes (DEGs) were identified by edgeR of the R platform...
2018: OncoTargets and Therapy
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