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Acute myeloid leukemia

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https://www.readbyqxmd.com/read/29444505/no-mutation-left-behind-the-impact-of-reporting-recurrent-genetic-abnormalities-on-outcomes-of-patients-with-acute-myeloid-leukemia
#1
Andrew M Brunner
No abstract text is available yet for this article.
February 14, 2018: Acta Haematologica
https://www.readbyqxmd.com/read/29442453/transcriptomic-analysis-of-the-pi3k-akt-signaling-pathway-reveals-the-dual-role-of-the-c-jun-oncogene-in-cytotoxicity-and-the-development-of-resistance-in-hl-60-leukemia-cells-in-response-to-arsenic-trioxide
#2
Joanna Roszak, Anna Smok-Pieniążek, Maciej Stępnik
BACKGROUND: Arsenic trioxide (ATO) is a well-recognized antileukemic drug used for the treatment of newly diagnosed and relapsed acute promyelocytic leukemia (APL). A major drawback of therapy with ATO is the development of APL cell resistance, the mechanisms of which are still not clear. OBJECTIVES: The aim of this study was to investigate the role of the PI3K/Akt signaling pathway in ATOtreated human acute myeloid leukemia (HL-60) cells and in ATO-resistant clones...
December 2017: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
https://www.readbyqxmd.com/read/29441994/decreased-mir-144-expression-as-a-non-invasive-biomarker-for-acute-myeloid-leukemia-patients
#3
Qiangqiang Zhao, Jianping Li, Shaobin Chen, Kuo Shen, Guo Ai, Xin Dai, Bangyou Xie, Yannan Shi, Shuxia Jiang, Jianming Feng, Wenqian Li
MicroRNAs are found to be stable in blood and they demonstrated tissue specific expression patterns. Thus, they may be used as potential non-invasive biomarkers of specific cancers. In the current study, we mainly focused on miR-144, which has never been studied in acute myeloid leukemia (AML). The expression of miR-144 was explored in the bone marrow and peripheral blood of AML patients and healthy control. The correlation between peripheral blood miR-144 level and key clinical parameters, including overall survival and prognostic value, was further explored...
April 1, 2017: Die Pharmazie
https://www.readbyqxmd.com/read/29441887/effect-of-npm1-type-b-mutation-on-the-proliferation-invasion-and-chemosensitivity-of-thp-1-leukemia-cells
#4
Jie Peng, Bin Fu, Gan Fu, Xielan Zhao, Xiaolin Li, Fangping Chen
Acute myeloid leukemia (AML) is the most malignant myeloid disorder in adults. AML with mutated nucleophosmin (NPM1) is regarded as an independent leukemia subtype. According to previous studies, the role of NPM1 gene A mutation in AML has been well established; however, another major type, NPM1 gene B type mutation (NPM1 MutB) has been rarely reported. In the present study, we found that overexpression of NPM1 MutB enhanced the proliferation and invasion of THP-1 AML cells through the regulation of TIMP-2, MMP-2, Ang-1, c-myc and CCND1; led to no significant change of apoptosis rate with the absence of chemotherapy agents, while enhanced the chemosensitivity of THP-1 AML cells to chemotherapy agents DNR and Ara-C through the regulation of Bax, Bcl-2 and caspase-3...
October 1, 2017: Die Pharmazie
https://www.readbyqxmd.com/read/29439669/a-novel-mir-375-hoxb3-cdca3-dnmt3b-regulatory-circuitry-contributes-to-leukemogenesis-in-acute-myeloid-leukemia
#5
Laixi Bi, Bin Zhou, Haiying Li, Licai He, Chunjing Wang, Zhonggai Wang, Liqing Zhu, Mengqian Chen, Shenmeng Gao
BACKGROUND: Acute myeloid leukemia (AML) is a heterogeneous group of hematopoietic malignancies due to sophisticated genetic mutations and epigenetic dysregulation. MicroRNAs (miRNAs), a class of small non-coding RNAs, are important regulators of gene expression in all biological processes, including leukemogenesis. Recently, miR-375 has been reported to be a suppressive miRNA in multiple types of cancers, but its underlying anti-leukemia activity in AML is largely unknown. METHODS: Quantitative reverse transcriptase PCR (qRT-PCR) was used to measure the expression of miR-375 and HOXB3 in leukemic cells and normal controls...
February 13, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29439554/pilot-study-on-mass-spectrometry-based-analysis-of-the-proteome-of-cd34%C3%A2-%C2%BAcd123%C3%A2-%C2%BA-progenitor-cells-for-the-identification-of-potential-targets-for-immunotherapy-in-acute-myeloid-leukemia
#6
Johannes R Schmidt, Elke Rücker-Braun, Katharina Heidrich, Malte von Bonin, Friedrich Stölzel, Christian Thiede, Jan M Middeke, Gerhard Ehninger, Martin Bornhäuser, Johannes Schetelig, Kristin Schubert, Martin von Bergen, Falk Heidenreich
Targeting of leukemic stem cells with specific immunotherapy would be an ideal approach for the treatment of myeloid malignancies, but suitable epitopes are unknown. The comparative proteome-level characterization of hematopoietic stem and progenitor cells from healthy stem cell donors and patients with acute myeloid leukemia has the potential to reveal differentially expressed proteins which can be used as surface-markers or as proxies for affected molecular pathways. We employed mass spectrometry methods to analyze the proteome of the cytosolic and the membrane fraction of CD34 and CD123 co-expressing FACS-sorted leukemic progenitors from five patients with acute myeloid leukemia...
February 12, 2018: Proteomes
https://www.readbyqxmd.com/read/29439315/downregulated-mir-217%C3%A2-expression-predicts-a-poor-outcome-in-acute%C3%A2-myeloid-leukemia
#7
Jinhua Yan, Guohe Wu, Jianlan Chen, Lifang Xiong, Guoan Chen, Ping Li
BACKGROUND: Circulating microRNAs (miRNAs) play an essential role in the development and progression of acute myeloid leukemia (AML). However, the clinical value of serum miR-217 in AML remained poorly known. OBJECTIVE: This study aimed to explore the clinical significance of serum miR-217 in AML. METHODS: Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was performed to detect miR-217 levels in the blood samples obtained from 89 AML patients and 60 healthy controls...
January 29, 2018: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/29439183/the-kit-and-pdgfra-switch-control-inhibitor-dcc-2618-blocks-growth-and-survival-of-multiple-neoplastic-cell-types-in-advanced-mastocytosis
#8
Mathias Schneeweiss, Barbara Peter, Siham Bibi, Gregor Eisenwort, Dubravka Smiljkovic, Katharina Blatt, Mohamad Jawhar, Daniela Berger, Gabriele Stefanzl, Susanne Herndlhofer, Georg Greiner, Gregor Hoermann, Emir Hadzijusufovic, Karoline V Gleixner, Peter Bettelheim, Klaus Geissler, Wolfgang R Sperr, Andreas Reiter, Michel Arock, Peter Valent
Systemic mastocytosis is a complex disease defined by abnormal growth and accumulation of neoplastic mast cells in various organs. Most patients exhibit a D816V-mutated variant of KIT, which confers resistance against imatinib. Clinical problems in systemic mastocytosis arise from mediator-related symptoms and/or organ destruction caused by malignant expansion of neoplastic mast cells and/or other myeloid cells in various organ systems. DCC-2618 is a spectrum-selective pan KIT and PDGFRA inhibitor which blocks KIT D816V and multiple other kinase-targets relevant to systemic mastocytosis...
February 8, 2018: Haematologica
https://www.readbyqxmd.com/read/29437791/a-phase-i-study-of-cpi-613-in-combination-with-high-dose-cytarabine-and-mitoxantrone-for-relapsed-or-refractory-acute-myeloid-leukemia
#9
Timothy S Pardee, Rebecca G Anderson, Kristin M Pladna, Scott Isom, Lais P Ghiraldeli, Lance D Miller, Jeff A Chou, Guangxu Jin, Wei Zhang, Leslie R Ellis, Dmitriy Berenzon, Dianna S Howard, David Hurd, Megan Manuel, Sarah Dralle, Susan Lyerly, Bayard L Powell
PURPOSE: CPI-613, a lipoate analog that inhibits pyruvate dehydrogenase (PDH) and α-ketogluterate dehydrogenase (KGDH) has activity in patients with myeloid malignancies. This study explored the role of mitochondrial metabolism in chemotherapy response, determined the maximally tolerated dose, efficacy and safety of CPI-613 combined with high dose cytarabine and mitoxantrone in patients with relapsed or refractory acute myeloid leukemia. METHODS: The role of mitochondrial response to chemotherapy was assessed in cell lines and animal models...
February 6, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29437468/dual-flt3-topk-inhibitor-with-activity-against-flt3-itd-secondary-mutations-potently-inhibits-acute-myeloid-leukemia-cell-lines
#10
Neetu Dayal, Clement Opoku-Temeng, Delmis E Hernandez, Moloud Aflaki Sooreshjani, Brandon A Carter-Cooper, Rena G Lapidus, Herman O Sintim
AIM: Approximately 30% of acute myeloid leukemia (AML) patients carry FLT3 tyrosine kinase domain (TKD) mutations or internal tandem duplication (FLT3-ITD). Currently there is a paucity of compounds that are active against drug-resistant FLT3-ITD, which contains secondary mutations in the TKD, mainly at residues D835/F691. RESULTS: HSD1169, a novel compound, is active against FLT3-ITD (D835 or F691). HSD1169 is also active against T-LAK cell-originated protein kinase (TOPK), a collaborating kinase that is highly expressed in AML cell lines...
February 13, 2018: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/29435332/more-is-less-less-is-more-or-does-it-really-matter-the-curious-case-of-impact-of-azacitidine-administration-schedules-on-outcomes-in-patients-with-myelodysplastic-syndromes
#11
Rory M Shallis, Amer M Zeidan
Myelodysplastic syndromes (MDS) encompass a diverse group of hematologic disorders characterized by ineffective and malignant hematopoiesis, peripheral cytopenias and significantly increased risk of progression to acute myeloid leukemia (AML). The hypomethylating agents (HMA) azacitidine and decitabine induce meaningful clinical responses in a significant subset of patients with MDS. Though never compared directly with decitabine, only azacitidine has improved overall survival (OS) compared to conventional care in a randomized trial in patients with higher-risk MDS...
2018: BMC Hematology
https://www.readbyqxmd.com/read/29435331/systematic-review-of-azacitidine-regimens-in-myelodysplastic-syndrome-and-acute-myeloid-leukemia
#12
Roman M Shapiro, Alejandro Lazo-Langner
Background: 5-Azacitidine administered as a 7-day dosing regimen (7-0-0) is approved in high risk IPSS myelodysplastic syndrome (MDS) patients. Alternative regimens such as a 5-day (5-0-0) or 7-day with a weekend break (5-2-2) are commonly used. No randomized controlled trial has been done directly comparing all three dosing regimens. The objective of this study was to compare the efficacies of the 5-0-0, 5-2-2, and 7-0-0 regimens in MDS and AML. Methods: A systematic review was conducted using MEDLINE, EMBASE and CENTRAL...
2018: BMC Hematology
https://www.readbyqxmd.com/read/29435155/assessment-of-a-new-genomic-classification-system-in-acute-myeloid-leukemia-with-a-normal-karyotype
#13
Jae-Sook Ahn, Hyeoung-Joon Kim, Yeo-Kyeoung Kim, Seung-Shin Lee, Seo-Yeon Ahn, Sung-Hoon Jung, Deok-Hwan Yang, Je-Jung Lee, Hee Jeong Park, Ja-Yeon Lee, Seung Hyun Choi, Chul Won Jung, Jun-Ho Jang, Hee Je Kim, Joon Ho Moon, Sang Kyun Sohn, Yoo Jin Lee, Jong-Ho Won, Sung-Hyun Kim, Zhaolei Zhang, TaeHyung Kim, Dennis Dong Hwan Kim
This study was performed to assess if a recently recommended genomic classification is predictive in patients with normal-karyotype (NK) acute myeloid leukemia (AML). A total of 393 patients were included. Analysis of genetic mutations was performed using targeted resequencing with an Illumina Hiseq 2000. We identified driver mutations across 40 genes, with one or more driver mutations identified in 95.7% of patients. The molecular subclassification was as follows: 34.6% patients (n = 136) with AML with the NPM1 mutation, 10...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29435140/triplications-of-human-chromosome-21-orthologous-regions-in-mice-result-in-expansion-of-megakaryocyte-erythroid-progenitors-and-reduction-of-granulocyte-macrophage-progenitors
#14
Chunhong Liu, Tao Yu, Zhuo Xing, Xiaoling Jiang, Yichen Li, Annie Pao, Justin Mu, Paul K Wallace, George Stoica, Andrei V Bakin, Y Eugene Yu
Individuals with Down syndrome (DS) frequently have hematopoietic abnormalities, including transient myeloproliferative disorder and acute megakaryoblastic leukemia which are often accompanied by acquired GATA1 mutations that produce a truncated protein, GATA1s. The mouse has been used for modeling DS based on the syntenic conservation between human chromosome 21 (Hsa21) and three regions in the mouse genome located on mouse chromosome 10 (Mmu10), Mmu16 and Mmu17. To assess the impact of the dosage increase of Hsa21 gene orthologs on the hematopoietic system, we characterized the related phenotype in the Dp(10)1Yey/+;Dp(16)1Yey/+;Dp(17)1Yey/+ model which carries duplications spanning the entire Hsa21 orthologous regions on Mmu10, Mmu16 and Mmu17, and the Dp(10)1Yey /+; Dp(16)1Yey /+; Dp(17)1Yey/+ ; Gata1 Yeym2 model which carries a Gata1s mutation we engineered...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29435107/discovery-and-functional-implications-of-a-mir-29b-1-mir-29a-cluster-polymorphism-in-acute-myeloid-leukemia
#15
Apollinaire Ngankeu, Parvathi Ranganathan, Violaine Havelange, Deedra Nicolet, Stefano Volinia, Bayard L Powell, Jonathan E Kolitz, Geoffrey L Uy, Richard M Stone, Steven M Kornblau, Michael Andreeff, Carlo M Croce, Clara D Bloomfield, Ramiro Garzon
We previously reported that microRNA (miR)-29b is down-regulated and has a tumor suppressor role in acute myeloid leukemia (AML). However, little is known about the mechanisms responsible for miR-29b expression downregulation in AML. In this work we screened for mutations that could affect miR-29b expression. Using Sanger sequencing, we identified a germline thymidine (T) base deletion within the miR-29b-1/miR-29a cluster precursor in 16% of AML patients. Remarkably we found a significant enrichment for the presence of the miR-29 polymorphism in core binding factor (CBF) newly diagnosed AML patients (n = 61/303; 20%) with respect to age, sex and race matched controls (n = 43/402:11%, P < 0...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29435104/niclosamide-suppresses-acute-myeloid-leukemia-cell-proliferation-through-inhibition-of-creb-dependent-signaling-pathways
#16
Hee-Don Chae, Nick Cox, Gary V Dahl, Norman J Lacayo, Kara L Davis, Samanta Capolicchio, Mark Smith, Kathleen M Sakamoto
CREB (cAMP Response Element Binding protein) is a transcription factor that is overexpressed in primary acute myeloid leukemia (AML) cells and associated with a decreased event-free survival and increased risk of relapse. We recently reported a small molecule inhibitor of CREB, XX-650-23, which inhibits CREB activity in AML cells. Structure-activity relationship analysis for chemical compounds with structures similar to XX-650-23 led to the identification of the anthelminthic drug niclosamide as a potent anti-leukemic agent that suppresses cell viability of AML cell lines and primary AML cells without a significant decrease in colony forming activity of normal bone marrow cells...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29434793/development-and-identification-of-set-transgenic-mice
#17
Siliang Xu, Xiaoqiang Liu, Lingling Gao, Boqun Xu, Jianmin Li, Chao Gao, Yugui Cui, Jiayin Liu
As a multifunctional protein involved in numerous biological processes, Set is expressed in several embryonic and adult organs. Furthermore, Set is overexpressed in numerous types of human cancers, including acute myeloid leukemia, breast cancer and pancreatic cancer. The expression of Set in germ cells is involved in gonad development, and the overexpression of Set has been observed in polycystic ovaries. In order to elucidate the physiological and pathological roles of Set, a Set transgenic mouse model was developed, in which the global overexpression of Set in adult tissues could be induced via the Cre/loxP system with the precise deletion of the Stop fragment in double-transgenic hybrids...
February 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29434724/combined-usage-of-wilms-tumor-gene-quantitative-analysis-and-multiparameter-flow-cytometry-for-minimal-residual-disease-monitoring-of-acute-myeloid-leukemia-patients-after-allogeneic-hematopoietic-stem-cells-transplantation
#18
Yingchan Hao, Yanhong Cheng, Quan Wu, Aimei Zhang, Xiaoxiao Jiang, Xiucai Xu
High expression of the Wilms' tumor gene (WT1) in acute myeloid leukemia (AML) has been considered as a sensitive marker of minimal residual disease (MRD). The present study investigated the significance of quantitative analysis of WT1 mRNA, combined with multiparameter flow cytometry (MFC) regarding its efficacy and prognostic as well as relapse prediction value for leukemia patients with hematopoietic stem cell transplantation. Reverse-transcription quantitative polymerase chain reaction analysis demonstrated that the expression of WT1 in the initial and relapse group was significant higher than that in the complete remission (CR) group (P<0...
February 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29434256/mathematical-modeling-of-the-impact-of-cytokine-response-of-acute-myeloid-leukemia-cells-on-patient-prognosis
#19
Thomas Stiehl, Anthony D Ho, Anna Marciniak-Czochra
Acute myeloid leukemia (AML) is a heterogeneous disease. One reason for the heterogeneity may originate from inter-individual differences in the responses of leukemic cells to endogenous cytokines. On the basis of mathematical modeling, computer simulations and patient data, we have provided evidence that cytokine-independent leukemic cell proliferation may be linked to early relapses and poor overall survival. Depending whether the model of cytokine-dependent or cytokine-independent leukemic cell proliferation fits to the clinical data, patients can be assigned to two groups that differ significantly with respect to overall survival...
February 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29433979/marrow-hypocellularity-but-not-residual-blast-count-or-receipt-of-reinduction-chemotherapy-is-prognostic-on-day-14-assessment-in-acute-myeloid-leukemia-patients-with-morphologic-residual-disease
#20
Thomas A Ollila, Adam J Olszewski, James N Butera, Matthew I Quesenberry, Peter J Quesenberry, John L Reagan
BACKGROUND: Induction chemotherapy for acute myeloid leukemia (AML) is based on the "7+3" cytarabine/anthracycline regimen. A nonhypocellular day 14 (D14) bone marrow sample with a blast count > 5% to 10% is suggestive of residual leukemia, for which a second course of induction chemotherapy has been recommended. Although the prognostic value of D14 bone marrow findings has been established, its use as a decision point is controversial because the benefit of repeat induction has been questioned...
January 31, 2018: Clinical Lymphoma, Myeloma & Leukemia
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