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https://www.readbyqxmd.com/read/28626363/hoxb4-increases-runx1-expression-to-promote-the-de-novo-formation-of-multipotent-hematopoietic-cells
#1
Nadine Teichweyde, Peter A Horn, Hannes Klump
BACKGROUND: The de novo generation of patient-specific hematopoietic stem and progenitor cells from induced pluripotent stem cells (iPSCs) has become a promising approach for cell replacement therapies in the future. However, efficient differentiation protocols for producing fully functional human hematopoietic stem cells are still missing. In the mouse model, ectopic expression of the human homeotic selector protein HOXB4 has been shown to enforce the development of hematopoietic stem cells (HSCs) in differentiating pluripotent stem cell cultures...
June 2017: Transfusion Medicine and Hemotherapy
https://www.readbyqxmd.com/read/28611288/an-aml1-eto-mir-29b-1-regulatory-circuit-modulates-phenotypic-properties-of-acute-myeloid-leukemia-cells
#2
Sayyed K Zaidi, Andrew W Perez, Elizabeth S White, Jane B Lian, Janet L Stein, Gary S Stein
Acute myeloid leukemia (AML) is characterized by an aggressive clinical course and frequent cytogenetic abnormalities that include specific chromosomal translocations. The 8;21 chromosomal rearrangement disrupts the key hematopoietic RUNX1 transcription factor, and contributes to leukemia through recruitment of co-repressor complexes to RUNX1 target genes, altered subnuclear localization, and deregulation of the myeloid gene regulatory program. However, a role of non-coding microRNAs (miRs) in t(8;21)-mediated leukemogenesis is minimally understood...
June 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28606225/-clinical-characteristics-and-prognostic-analysis-of-children-and-adolescents-over-10-years-of-age-with-acute-lymphoblastic-leukemia
#3
Jun Wu, Ai-Dong Lu, Le-Ping Zhang
OBJECTIVE: To explore the clinical characteristics and prognosis of children and adolescents over 10 years of age with acute lymphoblastic leukemia (ALL). METHODS: A total of 86 newly diagnosed ALL children and adolescents over 10 years of age (62 cases of B-ALL and 24 cases of T-ALL) were enrolled. Clinical characteristics, therapeutic effect and prognostic factors were retrospectively analyzed. Event-free survival (EFS) and overall survival (OS) rates were estimated by the Kaplan-Meier method...
June 2017: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/28598127/-correlations-between-aml1-eto-fusion-gene-and-clinical-features-of-acute-myeloid-leukemia-in-sichuan
#4
Xue-Mei Wang, Yuan-Xin Ye, Lian Yang, Xiao-Jun Lu, Bin-Wu Ying
OBJECTIVES: To determine the correlations between AML1-ETO fusion gene and clinical characteristics of patients with AML,and its association with the prognosis of AML-M2. METHODS: Medical records of 94 AML-M2 cases with positive AML1-ETO fusion gene and 51 AML-M2 cases with negative AML1-ETO gene were retrospective reviewed.Their clinical characteristics,treatment responses and prognostic outcomes were compared. RESULTS: No significant differences in the clinical symptoms,predominantly anemia,fever and hemorrhage,were found between the AML1-ETO fusion gene positive and negative AML-M2 (P>0...
November 2016: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28567073/quantitative-assessment-of-wilms-tumor-1-expression-by-real-time-quantitative-polymerase-chain-reaction-in-patients-with-acute-myeloblastic-leukemia
#5
Hossein Ayatollahi, Mohammad Hadi Sadeghian, Mahmood Naderi, Amir Hossein Jafarian, Seyyede Fatemeh Shams, Neda Motamedirad, Maryam Sheikhi, Afsane Bahrami, Sepideh Shakeri
BACKGROUND: The Wilms tumor 1 (WT1) gene is originally defined as a tumor suppressor gene and a transcription factor that overexpressed in leukemic cells. It is highly expressed in more than 80% of acute myeloid leukemia (AML) patients, both in bone marrow (BM) and in peripheral blood (PB), and it is used as a powerful and independent marker of minimal residual disease (MRD); we have determined the expression levels of the WT1 by real-time quantitative polymerase chain reaction (RQ-PCR) in PB and BM in 126 newly diagnosed AML patients...
2017: Journal of Research in Medical Sciences: the Official Journal of Isfahan University of Medical Sciences
https://www.readbyqxmd.com/read/28562359/blockage-of-foxp3-transcription-factor-dimerization-and-foxp3-aml1-interaction-inhibits-t-regulatory-cell-activity-sequence-optimization-of-a-peptide-inhibitor
#6
Teresa Lozano, Marta Gorraiz, Aritz Lasarte-Cía, Marta Ruiz, Obdulia Rabal, Julen Oyarzabal, Sandra Hervás-Stubbs, Diana Llopiz, Pablo Sarobe, Jesús Prieto, Noelia Casares, Juan José Lasarte
Although T regulatory cells (Treg) are essential for the prevention of autoimmune diseases, their immunoregulatory function restrains the induction of immune responses against cancer. Thus, development of inhibitors of FOXP3, a key transcription factor for the immunosuppressive activity of Treg, might give new therapeutic opportunities. In a previous work we identified a peptide (named P60) able to enter into the cells, bind to FOXP3, and impair Treg activity in vitro and in vivo. Here we show that P60 binds to the intermediate region of FOXP3 and inhibits its homodimerization as well as its interaction with the transcription factor AML1...
May 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28539478/a-novel-epigenetic-aml1-eto-thap10-mir-383-mini-circuitry-contributes-to-t-8-21-leukaemogenesis
#7
Yonghui Li, Qiaoyang Ning, Jinlong Shi, Yang Chen, Mengmeng Jiang, Li Gao, Wenrong Huang, Yu Jing, Sai Huang, Anqi Liu, Zhirui Hu, Daihong Liu, Lili Wang, Clara Nervi, Yun Dai, Michael Q Zhang, Li Yu
DNA methylation patterns are frequently deregulated in t(8;21) acute myeloid leukaemia (AML), but little is known of the mechanisms by which specific gene sets become aberrantly methylated. Here, we found that the promoter DNA methylation signature of t(8;21)(+) AML blasts differs from that of t(8;21)(-) AMLs. This study demonstrated that a novel hypermethylated zinc finger-containing protein, THAP10, is a target gene and can be epigenetically suppressed by AML1-ETO at the transcriptional level in t(8;21) AML...
May 24, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28516957/asxl2-is-essential-for-haematopoiesis-and-acts-as-a-haploinsufficient-tumour-suppressor-in-leukemia
#8
Jean-Baptiste Micol, Alessandro Pastore, Daichi Inoue, Nicolas Duployez, Eunhee Kim, Stanley Chun-Wei Lee, Benjamin H Durham, Young Rock Chung, Hana Cho, Xiao Jing Zhang, Akihide Yoshimi, Andrei Krivtsov, Richard Koche, Eric Solary, Amit Sinha, Claude Preudhomme, Omar Abdel-Wahab
Additional sex combs-like (ASXL) proteins are mammalian homologues of additional sex combs (Asx), a regulator of trithorax and polycomb function in Drosophila. While there has been great interest in ASXL1 due to its frequent mutation in leukemia, little is known about its paralog ASXL2, which is frequently mutated in acute myeloid leukemia patients bearing the RUNX1-RUNX1T1 (AML1-ETO) fusion. Here we report that ASXL2 is required for normal haematopoiesis with distinct, non-overlapping effects from ASXL1 and acts as a haploinsufficient tumour suppressor...
May 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28454473/methylation-pattern-of-preferentially-expressed-antigen-of-melanoma-in-acute-myeloid-leukemia-and-myelodysplastic-syndromes
#9
Ya-Zhen Qin, Yan-Huan Zhang, Xiao-Ying Qin, Hong-Hu Zhu
Preferentially expressed antigen of melanoma (PRAME), a tumor-associated antigen, is overexpressed in a variety of hematologic malignancies with a great variation in expression. The majority of patients with acute myeloid leukemia (AML) 1-eight-twenty one (ETO)(+) AML and a certain number of myelodysplastic syndromes (MDS) have an abnormally high increase in PRAME expression level. The landscape of PRAME methylation requires evaluation in order to determine the most relevant sites and the exact association of its methylation with expression level and type of disease...
April 2017: Oncology Letters
https://www.readbyqxmd.com/read/28436581/pediatric-acute-lymphoblastic-leukemia-with-t-1-19-tcf3-pbx1-in-taiwan
#10
Hsiu-Ju Yen, Shih-Hsiang Chen, Tsung-Yen Chang, Chao-Ping Yang, Dong-Tsamn Lin, Iou-Jih Hung, Kai-Hsin Lin, Jiann-Shiuh Chen, Chih-Cheng Hsiao, Tai-Tsung Chang, Te-Kao Chang, Ching-Tien Peng, Ming-Tsan Lin, Tang-Her Jaing, Hsi-Che Liu, Shiann-Tarng Jou, Meng-Yao Lu, Chao-Neng Cheng, Jiunn-Ming Sheen, Shyh-Shin Chiou, Giun-Yi Hung, Kang-Hsi Wu, Ting-Chi Yeh, Shih-Chung Wang, Rong-Long Chen, Hsiu-Hao Chang, Yung-Li Yang, Shu-Huey Chen, Shin-Nan Cheng, Yu-Hsiang Chang, Bow-Wen Chen, Yuh-Lin Hsieh, Fang-Liang Huang, Wan-Ling Ho, Jinn-Li Wang, Chia-Yau Chang, Yu-Hua Chao, Pei-Chin Lin, Yu-Chieh Chen, Yu-Mei Liao, Tung-Huei Lin, Lee-Yung Shih, Der-Cherng Liang
BACKGROUND: In childhood acute lymphoblastic leukemia (ALL), t(1;19)(q23;p13.3) with TCF3-PBX1 fusion is one of the most frequent translocations. Historically, it has been associated with poor prognosis. Intensive treatment, however, has improved its outcome. We determined the outcome of children with this genotype treated with contemporary intensive chemotherapy in Taiwan. PROCEDURE: In Taiwan Pediatric Oncology Group 2002 ALL studies, genotypes were determined by cytogenetic analysis and/or reverse transcriptase polymerase chain reaction assay...
April 24, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28381396/caspase-3-controls-aml1-eto-driven-leukemogenesis-via-autophagy-modulation-in-a-ulk1-dependent-manner
#11
Na Man, Yurong Tan, Xiao-Jian Sun, Fan Liu, Guoyan Cheng, Sarah M Greenblatt, Camilo Martinez, Daniel L Karl, Koji Ando, Ming Sun, Dan Hou, Bingyi Chen, Mingjiang Xu, Feng-Chun Yang, Zhu Chen, Saijuan Chen, Stephen D Nimer, Lan Wang
AML1-ETO (AE), a fusion oncoprotein generated by t(8;21), can trigger acute myeloid leukemia (AML) in collaboration with mutations including c-Kit, ASXL1/2, FLT3, N-RAS, and K-RAS. Caspase-3, a key executor among its family, plays multiple roles in cellular processes, including hematopoietic development and leukemia progression. Caspase-3 was revealed to directly cleave AE in vitro, suggesting that AE may accumulate in a Caspase-3-compromised background and thereby accelerate leukemogenesis. Therefore, we developed a Caspase-3 knockout genetic mouse model of AML and found that loss of Caspase-3 actually delayed AML1-ETO9a (AE9a)-driven leukemogenesis, indicating that Caspase-3 may play distinct roles in the initiation and/or progression of AML...
May 18, 2017: Blood
https://www.readbyqxmd.com/read/28360416/heterodimerization-of-aml1-eto-with-cbf%C3%AE-is-required-for-leukemogenesis-but-not-for-myeloproliferation
#12
V Thiel, B D Giaimo, P Schwarz, K Soller, V Vas, M Bartkuhn, T J Blätte, K Döhner, L Bullinger, T Borggrefe, H Geiger, F Oswald
The AML1/Runx1 transcription factor and its heterodimerization partner CBFβ are essential regulators of myeloid differentiation. The chromosomal translocation t(8;21), fusing the DNA binding domain of AML1 to the corepressor eight-twenty-one (ETO), is frequently associated with acute myeloid leukemia (AML) and generates the AML1/ETO (AE) fusion protein. AE represses target genes usually activated by AML1 and also affects the endogenous repressive function of ETO at Notch target genes. In order to analyze the contribution of CBFβ in AE-mediated leukemogenesis and deregulation of Notch target genes, we introduced two point mutations in a leukemia initiating version of AE in mice, called AE9a, that disrupt the AML1/CBFβ interaction (AE9aNT)...
March 31, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28349830/aberrant-aml1-gene-expression-in-the-diagnosis-of-childhood-leukemias-not-characterized-by-aml1-involved-cytogenetic-abnormalities
#13
Maria Adamaki, Spiros Vlahopoulos, George I Lambrou, Athanasios G Papavassiliou, Maria Moschovi
The AML1 ( acute myeloid leukemia 1) gene, a necessary prerequisite of embryonic hematopoiesis and a critical regulator of normal hematopoietic development, is one of the most frequently mutated genes in human leukemia, involving over 50 chromosome translocations and over 20 partner genes. In the few existing studies investigating AML1 gene expression in childhood leukemias, aberrant upregulation seems to specifically associate with AML1 translocations and amplifications. The aim of this study was to determine whether overexpression also extends to other leukemic subtypes than the ones karyotypically involving AML1...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28299660/etv6-runx1-acute-lymphoblastic-leukaemia-in-identical-twins
#14
Anthony M Ford, Mel Greaves
Acute leukaemia is the major subtype of paediatric cancer with a cumulative risk of 1 in 2000 for children up to the age of 15 years. Childhood acute lymphoblastic leukaemia (ALL) is a biologically and clinically diverse disease with distinctive subtypes; multiple chromosomal translocations exist within the subtypes and each carries its own prognostic relevance. The most common chromosome translocation observed is the t(12;21) that results in an in-frame fusion between the first five exons of ETV6 (TEL) and almost the entire coding region of RUNX1 (AML1)...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28299657/runx1-eto-leukemia
#15
Shan Lin, James C Mulloy, Susumu Goyama
AML1-ETO leukemia is the most common cytogenetic subtype of acute myeloid leukemia, defined by the presence of t(8;21). Remarkable progress has been achieved in understanding the molecular pathogenesis of AML1-ETO leukemia. Proteomic surveies have shown that AML-ETO forms a stable complex with several transcription factors, including E proteins. Genome-wide transcriptome and ChIP-seq analyses have revealed the genes directly regulated by AML1-ETO, such as CEBPA. Several lines of evidence suggest that AML1-ETO suppresses endogenous DNA repair in cells to promote mutagenesis, which facilitates acquisition of cooperating secondary events...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28272704/a-minicircuitry-comprised-of-microrna-9-and-sirt1-contributes-to-leukemogenesis-in-t-8-21-acute-myeloid-leukemia
#16
L Zhou, L Fu, N Lv, X-S Chen, J Liu, Y Li, Q-Y Xu, S Huang, X-D Zhang, L-P Dou, L L Wang, Y-H Li, L Yu
OBJECTIVE: The AML1-ETO fusion protein (AE) resulting from the t(8;21) translocation is highly related to the pathogenesis and development of leukemia. microRNA-9 (miR-9) acts as a tumor suppressor gene in AE-positive acute myeloid leukemia (AML). Silent mating type information regulation 2 homolog-1 (SIRT1) is overexpressed in most cancer cells by increasing proliferation as a tumorigenic gene. The present study was performed to investigate the underlying interaction between miR-9 and SIRT1 in AE-positive AML...
February 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28261265/new-insights-into-transcriptional-and-leukemogenic-mechanisms-of-aml1-eto-and-e2a-fusion-proteins
#17
Jian Li, Chun Guo, Nickolas Steinauer, Jinsong Zhang
BACKGROUND: Nearly 15% of acute myeloid leukemia (AML) cases are caused by aberrant expression of AML1-ETO, a fusion protein generated by the t(8;21) chromosomal translocation. Since its discovery, AML1-ETO has served as a prototype to understand how leukemia fusion proteins deregulate transcription to promote leukemogenesis. Another leukemia fusion protein, E2A-Pbx1, generated by the t(1;19) translocation, is involved in acute lymphoblastic leukemias (ALLs). While AML1-ETO and E2A-Pbx1 are structurally unrelated fusion proteins, we have recently shown that a common axis, the ETO/E-protein interaction, is involved in the regulation of both fusion proteins, underscoring the importance of studying protein-protein interactions in elucidating the mechanisms of leukemia fusion proteins...
August 2016: Frontiers in Biology
https://www.readbyqxmd.com/read/28220038/phosphatase-prl2-promotes-aml1-eto-induced-acute-myeloid-leukemia
#18
M Kobayashi, S Chen, Y Bai, C Yao, R Gao, X-J Sun, C Mu, T A Twiggs, Z-H Yu, H S Boswell, M C Yoder, R Kapur, J C Mulloy, Z-Y Zhang, Y Liu
No abstract text is available yet for this article.
June 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28129329/space-time-clustering-of-childhood-leukemia-evidence-of-an-association-with-etv6-runx1-tel-aml1-fusion
#19
Christian Kreis, Judith E Lupatsch, Felix Niggli, Matthias Egger, Claudia E Kuehni, Ben D Spycher
BACKGROUND: Many studies have observed space-time clustering of childhood leukemia (CL) yet few have attempted to elicit etiological clues from such clustering. We recently reported space-time clustering of CL around birth, and now aim to generate etiological hypotheses by comparing clustered and nonclustered cases. We also investigated whether the clustering resulted from many small aggregations of cases or from a few larger clusters. METHODS: We identified cases of persons born and diagnosed between 1985 and 2014 at age 0-15 years from the Swiss Childhood Cancer Registry...
2017: PloS One
https://www.readbyqxmd.com/read/28089879/clinical-outcome-of-autologous-hematopoietic-cell-transplantation-in-adult-patients-with-acute-myeloid-leukemia-who-may-benefit-from-autologous-hematopoietic-cell-transplantation
#20
Jae-Ho Yoon, Hee-Je Kim, Sung-Soo Park, Young-Woo Jeon, Sung-Eun Lee, Byung-Sik Cho, Ki-Seong Eom, Yoo-Jin Kim, Seok Lee, Chang-Ki Min, Seok-Goo Cho, Dong-Wook Kim, Jong-Wook Lee, Woo-Sung Min
The role of autologous hematopoietic cell transplantation (auto-HCT) for postremission therapy of acute myeloid leukemia is yet to be elucidated. We retrospectively analyzed 240 patients treated with auto-HCT in first remission. All patients were treated with standard induction chemotherapy, and CD34(+) stem cells were collected at each cycle of consolidation. Stem cells were infused after total body irradiation (1200 cGy), cytarabine (9 g/m(2)), and melphalan (100 mg/m(2)). Estimated 5-year overall survival, disease-free survival (DFS), cumulative incidence of relapse (CIR), and nonrelapse mortality were 58...
January 12, 2017: Biology of Blood and Marrow Transplantation
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