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https://www.readbyqxmd.com/read/28076841/clonal-evolution-in-therapy-related-neoplasms
#1
Emiliano Fabiani, Giulia Falconi, Luana Fianchi, Marianna Criscuolo, Tiziana Ottone, Laura Cicconi, Stefan Hohaus, Simona Sica, Massimiliano Postorino, Antonino Neri, Marta Lionetti, Giuseppe Leone, Francesco Lo-Coco, Maria Teresa Voso
Therapy-related myeloid neoplasms (t-MN) may occur as a late effect of cytotoxic therapy for a primary malignancy or autoimmune diseases in susceptible individuals. We studied the development of somatic mutations in t-MN, using a collection of follow-up samples from 14 patients with a primary hematologic malignancy, who developed a secondary leukemia (13 t-MN and 1 t-acute lymphoblastic leukemia), at a median latency of 73 months (range 18-108) from primary cancer diagnosis.Using Sanger and next generation sequencing (NGS) approaches we identified 8 mutations (IDH1 R132H, ASXL1 Y591*, ASXL1 S689*, ASXL1 R693*, SRSF2 P95H, SF3B1 K700E, SETBP1 G870R and TP53 Y220C) in seven of thirteen t-MN patients (54%), whereas the t-ALL patient had a t(4,11) translocation, resulting in the KMT2A/AFF1 fusion gene...
January 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28074072/targeting-bet-proteins-improves-the-therapeutic-efficacy-of-bcl-2-inhibition-in-t-cell-acute-lymphoblastic-leukemia
#2
S Peirs, V Frismantas, F Matthijssens, W Van Loocke, T Pieters, N Vandamme, B Lintermans, M P Dobay, G Berx, B Poppe, S Goossens, B C Bornhauser, J-P Bourquin, P Van Vlierberghe
Inhibition of anti-apoptotic BCL-2 has recently emerged as a promising new therapeutic strategy for the treatment of a variety of human cancers, including leukemia. Here, we used T-cell acute lymphoblastic leukemia as a model system to identify novel synergistic drug combinations with the BH3 mimetic venetoclax (ABT-199). In vitro drug screening in primary leukemia specimens that were derived from patients with high risk of relapse or relapse and cell lines revealed synergistic activity between venetoclax and the BET bromodomain inhibitor JQ1...
January 11, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28074066/preclinical-targeting-of-aggressive-t-cell-malignancies-using-anti-cd5-chimeric-antigen-receptor
#3
K H Chen, M Wada, K G Pinz, H Liu, K-W Lin, A Jares, A E Firor, X Shuai, H Salman, M Golightly, F Lan, L Senzel, L-H Leung, X Jiang, Y Ma
The outlook for T-cell malignancies remain poor due to the lack of effective therapeutic options. Chimeric antigen receptor (CAR) immunotherapy has recently shown promise in clinical trials for B-cell malignancies, however, designing CARs for T-cell based disease remain a challenge due to the shared surface antigen pool between normal and malignant T-cells. Normal T-cells express CD5 but NK (natural killer) cells do not, positioning NK cells as attractive cytotoxicity cells for CD5CAR design. Additionally, CD5 is highly expressed in T cell acute lymphoblastic leukemia (T-ALL) and peripheral T cell lymphomas (PTCLs)...
January 11, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28069602/oncogenic-zeb2-activation-drives-sensitivity-towards-kdm1a-inhibition-in-t-cell-acute-lymphoblastic-leukemia
#4
Steven Goossens, Sofie Peirs, Wouter Van Loocke, Jueqiong Wang, Mina Takawy, Filip Matthijssens, Stefan E Sonderegger, Katharina Haigh, Thao Nguyen, Niels Vandamme, Magdaline Costa, Catherine Carmichael, Filip Van Nieuwerburgh, Dieter Deforce, Oded Kleifeld, David J Curtis, Geert Berx, Pieter Van Vlierberghe, Jody J Haigh
Elevated expression of the Zinc finger E-box binding homeobox transcription factor-2 (ZEB2) is correlated with poor prognosis and patient outcome in a variety of human cancer subtypes. Using a conditional gain-of-function mouse model, we recently demonstrated that ZEB2 is an oncogenic driver of immature T-cell acute lymphoblastic leukemia (T-ALL), a heterogenic subgroup of human leukemia characterized by a high incidence of remission failure or hematological relapse after conventional chemotherapy. Here, we identified the Lysine-specific demethylase KDM1A as a novel interaction partner of ZEB2 and demonstrated that mouse and human T-ALLs with increased ZEB2 levels critically depend on KDM1A activity for survival...
January 9, 2017: Blood
https://www.readbyqxmd.com/read/28045622/use-of-minimal-residual-disease-assessment-to-redefine-induction-failure-in-pediatric-acute-lymphoblastic-leukemia
#5
David O'Connor, Anthony V Moorman, Rachel Wade, Jeremy Hancock, Ronald M R Tan, Jack Bartram, John Moppett, Claire Schwab, Katharine Patrick, Christine J Harrison, Rachael Hough, Nick Goulden, Ajay Vora, Sujith Samarasinghe
Purpose Our aim was to determine the role of end-of-induction (EOI) minimal residual disease (MRD) assessment in the identification and stratification of induction failure in patients with pediatric acute lymphoblastic leukemia (ALL) and to identify genetic abnormalities that drive disease in these patients. Patients and Methods Analysis included 3,113 patients who were treated in the Medical Research Council UKALL2003 multicenter randomized trial (NCT00222612) between 2003 and 2011. MRD was measured by using standardized real-time quantitative PCR...
January 3, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28028313/aberrant-activation-of-the-gimap-enhancer-by-oncogenic-transcription-factors-in-t-cell-acute-lymphoblastic-leukemia
#6
W-S Liau, S H Tan, P C T Ngoc, C Q Wang, V Tergaonkar, H Feng, Z Gong, M Osato, A T Look, T Sanda
The transcription factor TAL1/SCL is one of the most prevalent oncogenes in T-cell acute lymphoblastic leukemia (T-ALL), a malignant disorder resulting from leukemic transformation of thymus T-cell precursors. TAL1 is normally expressed in hematopoietic stem cells (HSCs) but is silenced in immature thymocytes. We hypothesize that TAL1 contributes to leukemogenesis by activating genes that are normally repressed in immature thymocytes. Herein, we identified a novel TAL1-regulated super-enhancer controlling the GIMAP locus, which resides within an insulated chromosomal locus in T-ALL cells...
December 28, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28027553/effect-of-radiation-and-non-radiation-environmental-factors-on-children-hematopoietic-system
#7
V G Bebeshko, K M Bruslova, V V Stankevych, N M Tsvietkova, L O Lyashenko, S G Galkina, T I Pushkaryova, V I Kolos, O Ye Kuznetsova, L O Honchar, S M Yatsemyrskii, Y M Samson
OBJECTIVE: Identification of impact of radiation and non radiation environmental factors on development of hematopoi etic abnormalities in children and justification of criteria for the increased risk groups of hematologic diseases. MATERIALS AND METHODS: The results of clinical and hematological survey of 1465 children living in Kyiv, Zhytomyr and Chernihiv regions for the period from 2008 to 2014 were presented. There were 777 children with anemia, 466 with changes in hemogram, 191 with acute leukemia...
December 2016: Problemy Radiat︠s︡iĭnoï Medyt︠s︡yny Ta Radiobiolohiï
https://www.readbyqxmd.com/read/28027552/state-of-erythroid-granulocyte-and-platelet-branches-of-hematopoiesis-on-stages-of-chemotherapy-in-children-with-acute-lymphoblastic-leukemia-who-were-exposed-to-ionizing-radiation-after-the-chornobyl-npp-accident
#8
V G Bebeshko, K M Bruslova, T I Pushkareva, N M Tsvyetkova, L O Lyashenko, O Ye Kuznyetsova, V F Kuzmenko, L O Gonchar, S M Yaatsemyrskyy
OBJECTIVE: Evaluation of proliferation and differentiation processes of progenitor cells in bone marrow by the com position of elements of erythroid, granulocyte and platelet branches of hematopoiesis on the treatment stages in children with acute lymphoblastic leukemia (ALL), who were exposed to radiation from the Chornobyl NPP accident. MATERIALS AND METHODS: The 46 children with ALL were studied, who lived in Kyiv, Zhytomyr and Chernihiv regions. Studies were conducted before the start of chemotherapy (ChT), on the 33 day of ChT (phase I), and after the com pletion of ChT (phase II)...
December 2016: Problemy Radiat︠s︡iĭnoï Medyt︠s︡yny Ta Radiobiolohiï
https://www.readbyqxmd.com/read/28024476/-clinical-characteristics-and-prognosis-of-21-cases-of-acute-lymphoblastic-leukemia-with-central-nervous-system-leukemia
#9
Xiang-Shu Jin, Lan Yang, Bian-Hong Wang, Hong-Hua Li, Li Yu, Yu Jing
OBJECTIVE: To investigate the clinical characteristics, therapeutic efficacy survival and prognosis of patients with adult acute lymphoblastic leukemia (ALL) accompanied by central nervous system leukemia (CNSL). METHODS: The clinical and cerebrospinal fluid (CSF) features, diagnosis and treatment, therapeutic efficacy and survival rate of 21 cases of acute lymphoblastic leukemia (ALL) with central nervous system involvement (CNSL) were analyzed retrospectively...
December 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28009354/rsk-mediated-nuclear-accumulation-of-the-cold-shock-y-box-protein-1-controls-proliferation-of-t-cells-and-t-all-blasts
#10
Steffi Gieseler-Halbach, Stefan Meltendorf, Mandy Pierau, Soenke Weinert, Florian H Heidel, Thomas Fischer, Juliane Handschuh, Ruediger C Braun-Dullaeus, Martin Schrappe, Jonathan A Lindquist, Peter R Mertens, Ulrich Thomas, Monika C Brunner-Weinzierl
Deregulated proliferation is key to tumor progression. Although unrestricted proliferation of solid tumor cells correlates with the cold-shock protein Y-box (YB)-binding protein-1 accumulation in the nuclei, little is known about its expression and function in hematopoietic malignancies, such as T-cell acute lymphoblastic leukemia (T-ALL). Here we show that YB-1 protein is highly enriched in the nuclei of activated T cells and malignant human T-ALL cell lines but not in resting T cells. YB-1 S(102) mutations that either mimic (S102D) or prevent phosphorylation (S102N) led to accumulation of YB-1 in the nucleus of T cells or strictly excluded it, respectively...
December 23, 2016: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28007943/fasting-inhibits-the-initiation-and-progression-of-b-all-and-t-all
#11
(no author information available yet)
Fasting upregulates the leptin receptor (LEPR) to block development of B-ALL and T-ALL, but not AML.
December 22, 2016: Cancer Discovery
https://www.readbyqxmd.com/read/28007775/beating-the-clock-in-t-cell-acute-lymphoblastic-leukemia
#12
William L Carroll, Iannis Aifantis, Elizabeth A Raetz
CDK4/6 inhibition was synergistic with dexmethasome and everolimus but antagonistic with conventional chemotherapy in T-cell acute lymphoblastic leukemia (T-ALL) pre-clinical models. Cyclin dependent kinase inhibition in combination with glucocorticoids and mTOR inhibition offers a unique therapeutic opportunity in T-ALL.
December 22, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28003999/synergistic-cytotoxic-effect-of-l-asparaginase-combined-with-decitabine-as-a-demethylating-agent-in-pediatric-t-all-with-specific-epigenetic-signature
#13
Salvatore Serravalle, Salvatore N Bertuccio, Annalisa Astolfi, Fraia Melchionda, Andrea Pession
T-Acute Lymphoblastic Leukemia (T-ALL) remains a subgroup of pediatric ALL, with a lower response to standard chemotherapy. Some recent studies established the fundamental role of epigenetic aberrations such as DNA hypermethylation, to influence patients' outcome and response to chemotherapy. Moreover, L-asparaginase is an important chemotherapeutic agent for treatment of ALL and resistance to this drug has been linked to ASNS expression, which can be silenced through methylation. Therefore, we tested whether the sensitivity of T-ALL cell lines towards L-asparaginase is correlated to the epigenetic status of ASNS gene and whether the sensitivity can be modified by concurrent demethylating treatment...
2016: BioMed Research International
https://www.readbyqxmd.com/read/28000876/mir-196b-mir-1290-participate-in-the-antitumor-effect-of-resveratrol-via-regulation-of-igfbp3-expression-in-acute-lymphoblastic-leukemia
#14
Wei Zhou, Shunqing Wang, Yi Ying, Ruiqing Zhou, Ping Mao
MicroRNAs play critical roles in the progression of acute lymphoblastic leukemia (ALL). Previous studies have indicated that miR-196b and miR-1290 play critical roles in T-cell ALL (T-ALL) and B-cell ALL (B-ALL), respectively. Resveratrol, a natural edible polyphenolic phytoalexin, possesses certain anticancer activities. Nevertheless, the mechanism involved in the regulation of ALL by resveratrol is still poorly understood. The present study aimed to reveal the potential mechanism underlying the antitumor effect of resveratrol in ALL focusing on miRNAs...
December 15, 2016: Oncology Reports
https://www.readbyqxmd.com/read/28000658/evaluation-of-left-ventricular-ejection-fractions-in-breast-cancer-patients-undergoing-long-term-trastuzumab-treatment
#15
Yong Sun, Tao Li, Yuanpeng Zhang, Qiwen Zhang
BACKGROUND The aim of this study was to assess the long-term clinical tolerance and cardiac safety during trastuzumab treatment for patients diagnosed as having breast cancer with human epidermal growth factor receptor 2 (HER2) overexpression. MATERIAL AND METHODS A total 105 female cases diagnosed as having breast cancer with high expression of Her2, were treated with trastuzumab (T). All of them underwent electrocardiography monitoring in the process of T treatment. Left ventricular ejection fractions (LVEFs) were estimated using echocardiography before the T treatment and every 3 months...
December 21, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/27997540/il-7-receptor-mutations-and-steroid-resistance-in-pediatric-t-cell-acute-lymphoblastic-leukemia-a-genome-sequencing-study
#16
Yunlei Li, Jessica G C A M Buijs-Gladdines, Kirsten Canté-Barrett, Andrew P Stubbs, Eric M Vroegindeweij, Willem K Smits, Ronald van Marion, Winand N M Dinjens, Martin Horstmann, Roland P Kuiper, Rogier C Buijsman, Guido J R Zaman, Peter J van der Spek, Rob Pieters, Jules P P Meijerink
BACKGROUND: Pediatric acute lymphoblastic leukemia (ALL) is the most common childhood cancer and the leading cause of cancer-related mortality in children. T cell ALL (T-ALL) represents about 15% of pediatric ALL cases and is considered a high-risk disease. T-ALL is often associated with resistance to treatment, including steroids, which are currently the cornerstone for treating ALL; moreover, initial steroid response strongly predicts survival and cure. However, the cellular mechanisms underlying steroid resistance in T-ALL patients are poorly understood...
December 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27941793/fasting-selectively-blocks-development-of-acute-lymphoblastic-leukemia-via-leptin-receptor-upregulation
#17
Zhigang Lu, Jingjing Xie, Guojin Wu, Jinhui Shen, Robert Collins, Weina Chen, Xunlei Kang, Min Luo, Yizhou Zou, Lily Jun-Shen Huang, James F Amatruda, Tamra Slone, Naomi Winick, Philipp E Scherer, Cheng Cheng Zhang
New therapeutic approaches are needed to treat leukemia effectively. Dietary restriction regimens, including fasting, have been considered for the prevention and treatment of certain solid tumor types. However, whether and how dietary restriction affects hematopoietic malignancies is unknown. Here we report that fasting alone robustly inhibits the initiation and reverses the leukemic progression of both B cell and T cell acute lymphoblastic leukemia (B-ALL and T-ALL, respectively), but not acute myeloid leukemia (AML), in mouse models of these tumors...
January 2017: Nature Medicine
https://www.readbyqxmd.com/read/27941168/wogonoside-exerts-growth-suppressive-effects-against-t-acute-lymphoblastic-leukemia-through-the-stat3-pathway
#18
R Xiao, M Gan, T Jiang
Wogonoside is the main flavonoid of the traditional Chinese medicinal herb Scutellaria baicalensis Georgi and has been found to induce growth suppression in myelogenous leukemia cells. However, its activity in T acute lymphoblastic leukemia (T-ALL) is still unclear. In this study, T-ALL cell lines MOLT-3 and Jurkat were exposed to different concentrations of wogonoside for 48 h, and cell viability, cell cycle distribution, and apoptosis were measured. The involvement of signal transducers and activators of transcription 3 (STAT3) signaling in the activity of wogonoside was checked...
December 9, 2016: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/27936393/suppression-of-protein-tyrosine-phosphatase-ptpn22-gene-induces-apoptosis-in-t-cell-leukemia-cell-line-jurkat-through-the-akt-and-erk-pathways
#19
Elham Baghbani, Behzad Baradaran, Fatemeh Pak, Leila Mohammadnejad, Daryoush Shanehbandi, Behzad Mansoori, Vahid Khaze, Noushin Montazami, Ali Mohammadi, Parviz Kokhaei
The aim of this study was to investigate the effect of specific PTPN22 small interfering RNAs (siRNAs) on the viability and induction of apoptosis in Jurkat cells and to evaluate apoptosis signaling pathways. In this study, Jurkat cells were transfected with specific PTPN22 siRNA. Relative PTPN22 mRNA expression was measured by Quantitative Real-time PCR. Western blotting was performed to determine the protein levels of PTPN22, AKT, P-AKT, ERK, and P-ERK. The cytotoxic effects of PTPN22 siRNA were determined using the MTT assay...
December 6, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27932323/targeting-hedgehog-in-t-all
#20
Shai Izraeli
No abstract text is available yet for this article.
December 8, 2016: Blood
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