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https://www.readbyqxmd.com/read/28229259/acidicapsa-ferrireducens-sp-nov-acidicapsa-acidiphila-sp-nov-and-granulicella-acidiphila-sp-nov-novel-acidobacteria-isolated-from-metal-rich-acidic-waters
#1
Carmen Falagán, Bärbel Foesel, Barrie Johnson
Four novel strains of Acidobacteria were isolated from water samples taken from pit lakes at two abandoned metal mines in the Iberian Pyrite Belt mining district, south-west Spain. Three of the isolates belong to the genus Acidicapsa (MCF9(T), MCF10(T), and MCF14) and one of them to the genus Granulicella (MCF40(T)). All isolates are moderately acidophilic (pH growth optimum 3.8-4.1) and mesophilic (temperature growth optima 30-32 °C). Isolates MCF10(T) and MCF40(T) grew at pH lower (<3.0) than previously reported for all other acidobacteria...
February 22, 2017: Extremophiles: Life Under Extreme Conditions
https://www.readbyqxmd.com/read/28225168/correlations-between-epstein-barr-virus-and-acute-leukemia
#2
Hongzai Guan, Hongxia Miao, Na Ma, Wei Lu, Bing Luo
Infection with Epstein-Barr virus (EBV) may be correlated to the onset of acute leukemia (AL). Studies were performed to investigate the relationship between EBV infection and immunophenotyping of acute lymphoblastic leukemia (ALL) and chromosome aberrations. Additionally, the effects of EBV on clinical prognosis were described. Fluorescence quantitative polymerase chain reaction (FQ-PCR) was used to detect EBV-DNA copy numbers from bone marrow in 110 cases of patients with ALL, 75 cases of patients with myeloid leukemia (AML) and 37 cases of hematologically healthy control subjects...
February 22, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28211568/targeted-therapies-for-t-cell-acute-lymphoblastic-leukaemia-t-all-what-makes-t-all-tyk
#3
EDITORIAL
David J Curtis
No abstract text is available yet for this article.
February 17, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28195849/detection-and-alterations-of-acetylcarnitine-in-human-skeletal-muscles-by-1h-mrs-at-7-t
#4
Radka Klepochová, Ladislav Valkovič, Martin Gajdošík, Thomas Hochwartner, Harald Tschan, Michael Krebs, Siegfried Trattnig, Martin Krššák
OBJECTIVES: The aims of this study were to detect the acetylcarnitine resonance line at 2.13 ppm in the human vastus lateralis and soleus muscles, assess T1 and T2 relaxation times, and investigate the diurnal and exercise-related changes in absolute concentration noninvasively, using proton magnetic resonance spectroscopy at 7 T. MATERIALS AND METHODS: All measurements were performed on a 7 T whole-body Magnetom MR system with a 28-channel knee coil. Five healthy, moderately trained volunteers participated in the assessment of the detectability, repeatability, and relaxation times of acetylcarnitine...
February 10, 2017: Investigative Radiology
https://www.readbyqxmd.com/read/28179281/scl-tal1-a-multi-faceted-regulator-from-blood-development-to-disease
#5
Catherine Porcher, Hedia Chagraoui, Maiken S Kristiansen
SCL/TAL1 is an essential transcription factor in normal and malignant hematopoiesis. It is required for specification of the blood program during development, adult hematopoietic stem cell (HSC) survival and quiescence, and terminal maturation of select blood lineages. Following ectopic expression, SCL contributes to oncogenesis in T-cell acute lymphoblastic leukemia (T-ALL). Remarkably, SCL's activities are all mediated through nucleation of a core quaternary protein complex (SCL:E-protein:LMO2:LDB1) and dynamic recruitment of conserved combinatorial associations of additional regulators in a lineage- and stage-specific context...
February 8, 2017: Blood
https://www.readbyqxmd.com/read/28174276/synergistic-antileukemic-therapies-in-notch1-induced-t-all
#6
Marta Sanchez-Martin, Alberto Ambesi-Impiombato, Yue Qin, Daniel Herranz, Mukesh Bansal, Tiziana Girardi, Elisabeth Paietta, Martin S Tallman, Jacob M Rowe, Kim De Keersmaecker, Andrea Califano, Adolfo A Ferrando
The Notch1 gene is a major oncogenic driver and therapeutic target in T-cell acute lymphoblastic leukemia (T-ALL). However, inhibition of NOTCH signaling with γ-secretase inhibitors (GSIs) has shown limited antileukemic activity in clinical trials. Here we performed an expression-based virtual screening to identify highly active antileukemic drugs that synergize with NOTCH1 inhibition in T-ALL. Among these, withaferin A demonstrated the strongest cytotoxic and GSI-synergistic antileukemic effects in vitro and in vivo...
February 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28171800/epigenetic-drug-combination-overcomes-osteoblast-induced-chemoprotection-in-pediatric-acute-lymphoid-leukemia
#7
Anthony Quagliano, Anilkumar Gopalakrishnapillai, Sonali P Barwe
Although there has been much progress in the treatment of acute lymphoblastic leukemia (ALL), decreased sensitivity to chemotherapy remains a significant issue. Recent studies have shown how interactions with the bone marrow microenvironment can protect ALL cells from chemotherapy and allow for the persistence of the disease. Epigenetic drugs have been used for the treatment of ALL, but there are no reports on whether these drugs can overcome bone marrow-induced chemoprotection. Our study investigates the ability of the DNA methyltransferase inhibitor azacitidine and the histone deacetylase inhibitor panobinostat to overcome chemoprotective effects mediated by osteoblasts...
January 27, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28159681/the-dual-specificity-pi3k-mtor-inhibitor-pki-587-displays-efficacy-against-t-cell-acute-lymphoblastic-leukemia-t-all
#8
Mohiuddin Gazi, Sausan A Moharram, Alissa Marhäll, Julhash U Kazi
Although significant improvements have been made in the treatment of acute lymphoblastic leukemia (ALL), there is a substantial subset of high-risk T-cell ALL (T-ALL) patients with relatively poor prognosis. Like in other leukemia types, alterations of the PI3K/mTOR pathway are predominant in ALL which is also responsible for treatment failure and relapse. In this study, we show that relapsed T-ALL patients display an enrichment of the PI3K/mTOR pathway. Using a panel of inhibitors targeting multiple components of the PI3K/mTOR pathway, we observed that the dual-specific PI3K/mTOR inhibitor PKI-587 was the most selective inhibitor for T-ALL cells dependent on the PI3K/mTOR pathway...
February 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28157215/identification-of-a-genetically-defined-ultra-high-risk-group-in-relapsed-pediatric-t-lymphoblastic-leukemia
#9
P Richter-Pechańska, J B Kunz, J Hof, M Zimmermann, T Rausch, O R Bandapalli, E Orlova, G Scapinello, J C Sagi, M Stanulla, M Schrappe, G Cario, R Kirschner-Schwabe, C Eckert, V Benes, J O Korbel, M U Muckenthaler, A E Kulozik
In the search for genes that define critical steps of relapse in pediatric T-cell acute lymphoblastic leukemia (T-ALL) and can serve as prognostic markers, we performed targeted sequencing of 313 leukemia-related genes in 214 patients: 67 samples collected at the time of relapse and 147 at initial diagnosis. As relapse-specific genetic events, we identified activating mutations in NT5C2 (P=0.0001, Fisher's exact test), inactivation of TP53 (P=0.0007, Fisher's exact test) and duplication of chr17:q11.2-24.3 (P=0...
February 3, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28156199/influence-of-test-distance-on-stereoacuity-in-intermittent-exotropia
#10
Yukari Seki, Akemi Wakayama, Rika Takahashi, Ikumi Umebara, Fumi Tanabe, Kosuke Abe, Yoshikazu Shimomura
AIMS: To investigate influence of test distance on stereoacuity in intermittent exotropia (X[T]) using the same test conditions for both near and far distances. METHODS: Subjects were 38 consecutive patients with X(T). All the patients were between ages 6 and 15 years and had decimal visual acuity of 1.0 or better. Another inclusion criterion was presence of phoric condition at near and far distances. Stereoacuity was measured at a near distance of 40 cm and at a far distance of 5 m...
February 3, 2017: Strabismus
https://www.readbyqxmd.com/read/28152513/propiece-il-1%C3%AE-facilitates-the-growth-of-acute-t-lymphocytic-leukemia-cells-through-the-activation-of-nf-%C3%AE%C2%BAb-and-sp1
#11
Yinsheng Zhang, Xiao Yu, Dandan Lin, Lei Lei, Bo Hu, Fengzhang Cao, Yu Mei, Depei Wu, Haiyan Liu
Interleukin 1α (IL-1α) is a pro-inflammatory cytokine that possesses multiple immune-regulatory functions. It is mainly expressed as the cell-associated form and not actively secreted in healthy tissues. The intracellular IL-1α has been shown to be a chromatin-associated cytokine and can affect transcription. There are spontaneous expressions of IL-1α in acute lymphocytic leukemia (ALL) blasts. However, the role of nuclear-localized IL-1α in ALL is not clear. Here we showed that overexpression of the nuclear form of IL-1α (propiece IL-1α) could promote proliferation and reduce apoptosis of T-ALL cells...
February 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28151996/nkl-homeobox-gene-activities-in-hematopoietic-stem-cells-t-cell-development-and-t-cell-leukemia
#12
Stefan Nagel, Claudia Pommerenke, Michaela Scherr, Corinna Meyer, Maren Kaufmann, Karin Battmer, Roderick A F MacLeod, Hans G Drexler
T-cell acute lymphoblastic leukemia (T-ALL) cells represent developmentally arrested T-cell progenitors, subsets of which aberrantly express homeobox genes of the NKL subclass, including TLX1, TLX3, NKX2-1, NKX2-5, NKX3-1 and MSX1. Here, we analyzed the transcriptional landscape of all 48 members of the NKL homeobox gene subclass in CD34+ hematopoietic stem and progenitor cells (HSPCs) and during lymphopoiesis, identifying activities of nine particular genes. Four of these were expressed in HSPCs (HHEX, HLX1, NKX2-3 and NKX3-1) and three in common lymphoid progenitors (HHEX, HLX1 and MSX1)...
2017: PloS One
https://www.readbyqxmd.com/read/28151717/synergistic-drug-combinations-with-a-cdk4-6-inhibitor-in-t-cell-acute-lymphoblastic-leukemia
#13
Yana Pikman, Gabriela Alexe, Giovanni Roti, Amy Saur Conway, Andrew Furman, Emily S Lee, Andrew E Place, Sunkyu Kim, Chitra Saran, Rebecca Modiste, David M Weinstock, Marian Harris, Andrew L Kung, Lewis B Silverman, Kimberly Stegmaier
PURPOSE: While significant progress has been made in the treatment of T-cell acute lymphoblastic leukemia (T-ALL), many patients will require additional therapy for relapsed/refractory disease. Cyclin D3 (CCND3) and CDK6 are highly expressed in T-ALL and have been effectively targeted in mutant NOTCH1-driven mouse models of this disease with a CDK4/6 small-molecule inhibitor. Combination therapy, however, will be needed for the successful treatment of human disease. EXPERIMENTAL DESIGN: We performed preclinical drug testing using a panel of T-ALL cell lines first with LEE011, a CDK4/6 inhibitor, and next with the combination of LEE011 with a panel of drugs relevant to T-ALL treatment...
November 9, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28143869/stabilization-of-notch1-by-the-hsp90-chaperon-is-crucial-for-t-cell-leukemogenesis
#14
Zhaojing Wang, Yufeng Hu, Daibiao Xiao, Jingchao Wang, Chuntao Liu, Yisheng Xu, Xiaomeng Shi, Peng Jiang, Liang Huang, Peng Li, Hudan Liu, Guoliang Qing
PURPOSE: Notch1 deregulation is assuming a focal role in T-cell acute lymphoblastic leukemia (T-ALL). Despite tremendous advances in our understanding of Notch1 transcriptional programs, the mechanisms by which Notch1 stability and turnover are regulated remain obscure. The goal of the present study is to identify intracellular Notch1 (ICN1, the activated form of Notch1) binding partner(s) regulating its stability and activity. EXPERIMENTAL DESIGN: We employed immunoaffinity purification to identify ICN1-associating partner and used co-immunoprecipitation to verify the endogenous protein interaction...
January 31, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28142295/identification-of-a-tumor-suppressor-network-in-t-cell-leukemia
#15
Stefan Nagel, Claudia Pommerenke, Corinna Meyer, Maren Kaufmann, Roderick A F MacLeod, Hans G Drexler
To identify novel cancer-related genes targeted by copy number alterations, we performed genomic profiling of T-cell acute lymphoblastic leukemia (T-ALL) cell lines. In 3/8, we identified a shared deletion at chromosomal position 2p16.3-p21. Within the minimally deleted region, we recognized several candidate tumor suppressor (TS) genes, including FBXO11 and FOXN2. An additional deletion at chromosome 14q23.2-q32.11 included FOXN3, highlighting this class of FOX genes as potential TS. Quantitative expression analyses of FBXO11, FOXN2, and FOXN3 confirmed reduced transcript levels in the identified cell lines...
January 31, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28123582/ets-related-gene-is-a-novel-prognostic-factor-in-childhood-acute-lymphoblastic-leukemia
#16
Hai-Zhao Zhao, Ming Jia, Ze-Bin Luo, Xiao-Jun Xu, Si-Si Li, Jing-Ying Zhang, Xiao-Ping Guo, Yong-Min Tang
The ETS-related gene (ERG) has been demonstrated to be associated with overall survival in cytogenetically normal acute myeloid leukemia and acute T cell-lymphoblastic leukemia (T-ALL) in adult patients. However, there are no data available regarding the impact of ERG expression on childhood ALL. In the present study, ERG expression levels were analyzed in bone marrow samples from 119 ALL pediatric patients. ALL patients demonstrated higher ERG expression compared with the controls (P<0.0001). In addition, low ERG expression identified a group of patients with higher white blood cell counts (P=0...
January 2017: Oncology Letters
https://www.readbyqxmd.com/read/28122742/ex-vivo-drug-response-profiling-detects-recurrent-sensitivity-patterns-in-drug-resistant-all
#17
Viktoras Frismantas, Maria Pamela Dobay, Anna Rinaldi, Joelle Tchinda, Samuel H Dunn, Joachim Kunz, Paulina Richter-Pechanska, Blerim Marovca, Orrin Pail, Silvia Jenni, Ernesto Diaz-Flores, Bill H Chang, Timothy J Brown, Robert H Collins, Sebastian Uhrig, Gnana P Balasubramanian, Obul R Bandapalli, Salome Higi, Sabrina Eugster, Pamela Voegeli, Mauro Delorenzi, Gunnar Cario, Mignon L Loh, Martin Schrappe, Martin Stanulla, Andreas E Kulozik, Martina U Muckenthaler, Vaskar Saha, Julie A Irving, Roland Meisel, Thomas Radimerski, Arend Von Stackelberg, Cornelia Eckert, Jeffrey W Tyner, Peter Horvath, Beat C Bornhauser, Jean-Pierre Bourquin
Drug sensitivity and resistance testing on diagnostic leukemia samples should provide important functional information to guide actionable target and biomarker discovery. We provide proof of concept data by profiling 60 drugs on 68 acute lymphoblastic leukemia (ALL) samples mostly from resistant disease in co-cultures on bone marrow stromal cells. Patient-derived xenografts retained the original pattern of mutations found in the matched patient material. Stromal co-culture did not prevent leukemia cell cycle activity, while a specific sensitivity profile to cell cycle related drugs identified samples with higher cell proliferation both in vitro and in vivo as leukemia xenografts...
January 25, 2017: Blood
https://www.readbyqxmd.com/read/28122332/the-homeoprotein-dlx5-drives-murine-t-cell-lymphomagenesis-by-directly-transactivating-notch-and-upregulating-akt-signaling
#18
Yinfei Tan, Eleonora Sementino, Jinfei Xu, Jianming Pei, Zemin Liu, Timothy K Ito, Kathy Q Cai, Suraj Peri, Andres J P Klein-Szanto, David L Wiest, Joseph R Testa
Homeobox genes play a critical role in embryonic development, but they have also been implicated in cancer through mechanisms that are largely unknown. While not expressed during normal T-cell development, homeobox transcription factor genes can be reactivated via recurrent chromosomal rearrangements in human T-cell acute leukemia/lymphoma (T-ALL), a malignancy often associated with activated Notch and Akt signaling. To address how epigenetic reprogramming via an activated homeobox gene might contribute to T-lymphomagenesis, we investigated a transgenic mouse model with thymocyte-specific overexpression of the Dlx5 homeobox gene...
January 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28115373/the-genetics-and-molecular-biology-of-t-all
#19
Tiziana Girardi, Carmen Vicente, Jan Cools, Kim De Keersmaecker
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy caused by the accumulation of genomic lesions that affect the development of T-cells. Since many years, it has been established that deregulated expression of transcription factors, impairment of the CDKN2A/2B cell cycle regulators and hyperactive NOTCH1 signaling play prominent roles in the pathogenesis of this leukemia. In the past decade, systematic screening of T-ALL genomes by high resolution copy number arrays and next- generation sequencing technologies has revealed that T-cell progenitors accumulate additional mutations affecting JAK/STAT signaling, protein translation and epigenetic control, providing novel attractive targets for therapy...
January 23, 2017: Blood
https://www.readbyqxmd.com/read/28115368/the-notch1-myc-highway-towards-t-cell-acute-lymphoblastic-leukemia
#20
Marta Sanchez-Martin, Adolfo Ferrando
T cell acute lymphoblastic leukemia (T-ALL) is a highly proliferative hematologic malignancy resulting from the transformation of immature T-cell progenitors. Aberrant cell growth and proliferation in T-ALL lymphoblasts are sustained by activation of strong oncogenic drivers promoting cell anabolism and cell cycle progression. Oncogenic NOTCH signaling, which is activated in over 65% of T-ALL cases by activating mutations in the NOTCH1 gene, has emerged as a major regulator of leukemia cell growth and metabolism...
January 23, 2017: Blood
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