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Dominic Gascho, Bettina Huber, Stephan A Bolliger, Michael J Thali, Sarah Schaerli
No abstract text is available yet for this article.
October 24, 2016: Forensic Science, Medicine, and Pathology
Annalisa Lonetti, Alessandra Cappellini, Alice Bertaina, Franco Locatelli, Andrea Pession, Francesca Buontempo, Camilla Evangelisti, Cecilia Evangelisti, Ester Orsini, Laura Zambonin, Luca Maria Neri, Alberto Maria Martelli, Francesca Chiarini
BACKGROUND: Although in recent years, the introduction of novel chemotherapy protocols has improved the outcome of T cell acute lymphoblastic leukemia (T-ALL) patients, refractory and/or relapsing disease remains a foremost concern. In this context, a major contribution was provided by the introduction of the nucleoside analog nelarabine, approved for salvage treatment of T-ALL patients with refractory/relapsed disease. However, nelarabine could induce a life-threatening, dose-dependent neurotoxicity...
October 24, 2016: Journal of Hematology & Oncology
Roderick J Finlayson, Atikun Thonnagith, Maria Francisca Elgueta, Jordi Perez, John-Paul B Etheridge, De Q H Tran
BACKGROUND AND OBJECTIVES: Novel multitined cannulae constitute an attractive option for ultrasound-guided radiofrequency neurotomy of cervical medial branches. The deployment tines increase the cannula's active area, thus altering its lesion size. Despite their theoretical benefits, multitined cannulae have not been assessed. In this bench study, we sought to investigate the lesions produced by a standard 18-gauge and 2 commercially available multitined deployment cannulae. We created ex vivo models to evaluate lesion morphology at a periosteal interface using approach angles likely to be encountered during an ultrasound-guided technique...
October 21, 2016: Regional Anesthesia and Pain Medicine
Charlotte V Cox, Paraskevi Diamanti, John P Moppett, Allison Blair
A significant number of children with T-lineage acute lymphoblastic leukemia (T-ALL) fail to respond to therapy and experience early relapse. CD99 has been shown to be overexpressed on T-ALL cells and is considered to be a reliable detector of the disease. However, the relevance of CD99 overexpression in ALL has not been investigated in a functional context. The aim of this study was to investigate the functional capacity of CD99+ cells in childhood ALL and determine the suitability of CD99 as a therapeutic target...
2016: PloS One
Jolanta Skalska-Sadowska, Małgorzata Dawidowska, Bronisława Szarzyńska-Zawadzka, Małgorzata Jarmuż-Szymczak, Joanna Czerwińska-Rybak, Ludomiła Machowska, Katarzyna Derwich
We report a pediatric case of acute T-lymphoblastic leukemia (T-ALL) with NOTCH1(wt) , FBXW7(wt) , STIL/TAL1, and PTEN (exons 2, 3, 4, 5) monoallelic deletions, biallelic CDKN2A/B deletion, and a minor t(8;14)(q24;q11)-positive subclone. Undetectable by a flow cytometric minimal residual disease assay, the t(8;14)(q24;q11) subclone expanded as detected by fluorescence in situ hybridization from 5% at diagnosis to 26% before consolidation and 100% at relapse bearing a monoallelic deletion (exons 2, 3) with a new frameshift mutation of PTEN and the same set of remaining molecular alterations...
October 19, 2016: Pediatric Blood & Cancer
Ying Wang, Bingyu Chen, Zhen Wang, Wei Zhang, Ke Hao, Yu Chen, Kaiqiang Li, Tongtong Wang, Yiwei Xie, Zhihui Huang, Xiangmin Tong
Marsdenia tenacissimae extraction (MTE) as a traditional Chinese herb has long been used to treat some diseases such as tumors in China. However, the potential effectiveness of MTE in leukemia has not yet been fully understood, and the related molecular mechanism is still unknown. In the present study, we aimed to evaluate the effects of MTE on the proliferation and apoptosis of Jurkat cells (T-ALL lines) and lymphocytes from T-ALL (T-cell acute lymphoblastic leukemia) patients. Firstly, CCK8 assays and flow cytometry assays revealed that MTE dose-dependently reduced the proliferation of Jurkat cells by arresting cell cycle at S phase...
October 14, 2016: Oncotarget
Edwin D Hawkins, Delfim Duarte, Olufolake Akinduro, Reema A Khorshed, Diana Passaro, Malgorzata Nowicka, Lenny Straszkowski, Mark K Scott, Steve Rothery, Nicola Ruivo, Katie Foster, Michaela Waibel, Ricky W Johnstone, Simon J Harrison, David A Westerman, Hang Quach, John Gribben, Mark D Robinson, Louise E Purton, Dominique Bonnet, Cristina Lo Celso
It is widely accepted that complex interactions between cancer cells and their surrounding microenvironment contribute to disease development, chemo-resistance and disease relapse. In light of this observed interdependency, novel therapeutic interventions that target specific cancer stroma cell lineages and their interactions are being sought. Here we studied a mouse model of human T-cell acute lymphoblastic leukaemia (T-ALL) and used intravital microscopy to monitor the progression of disease within the bone marrow at both the tissue-wide and single-cell level over time, from bone marrow seeding to development/selection of chemo-resistance...
October 17, 2016: Nature
Joy Benadiba, Celia Rosilio, Marielle Nebout, Vera Heimeroth, Zouhour Neffati, Alexandra Popa, Didier Mary, Emmanuel Griessinger, Véronique Imbert, Nicolas Sirvent, Jean-François Peyron
Iron is an essential nutrient, acting as a catalyst for metabolic reactions that are fundamental to cell survival and proliferation. Iron complexed to transferrin is delivered to the metabolism after endocytosis via the CD71 surface receptor. We found that transformed cells from a murine PTEN-deficient T-cell lymphoma model and from T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/T-LL) cell lines overexpress CD71. As a consequence, the cells developed an addiction toward iron whose chelation by deferoxamine (DFO) dramatically affected their survival to induce apoptosis...
October 13, 2016: Leukemia & Lymphoma
Xianjin Zhu, Yanfang Song, Conglian Wu, Chuxi Pan, Pingxia Lu, Meihua Wang, Peizheng Zheng, Rongfen Huo, Chenqing Zhang, Wanting Li, Yulin Lin, Yingping Cao, Ningli Li
Cyr61 (CCN1) is the product of a growth factor-inducible immediate early gene and is involved in cell adhesion, survival, proliferation, and differentiation. Cyr61 is overexpressed in human tumors and is involved in the development of tumors. However, the role that Cyr61 plays in acute lymphoblastic leukemia (ALL) cells remains undetermined. The aim of this study was to identify the role of Cyr61 in regulating ALL cell survival. Here, we found that the level of Cyr61 was increased in the plasma and bone marrow (BM) from ALL patients compared with samples from normal control patients...
October 11, 2016: Scientific Reports
Mareike Doerrenberg, Andreas Kloetgen, Kebria Hezaveh, Wilhelm Wössmann, Kirsten Bleckmann, Martin Stanulla, Martin Schrappe, Alice C McHardy, Arndt Borkhardt, Jessica I Hoell
For reasons not yet understood, nearly all infants with acute lymphoblastic leukemia (ALL) are diagnosed with the B-cell type, with T-ALL in infancy representing a very rare exception. Clinical and molecular knowledge about infant T-ALL is still nearly completely lacking and it is also still unclear whether it represents a distinct disease compared to childhood T-ALL. To address this, we performed exome sequencing of three infant cases, which enabled the detection of mutations in NOTCH2, NOTCH3, PTEN, and KRAS...
September 26, 2016: Genes, Chromosomes & Cancer
David J Torres, Judy L Cannon, Ulises M Ricoy, Christopher Johnson
Microarrays are a powerful tool for studying differential gene expression. However, lists of many differentially expressed genes are often generated, and unraveling meaningful biological processes from the lists can be challenging. For this reason, investigators have sought to quantify the statistical probability of compiled gene sets rather than individual genes. The gene sets typically are organized around a biological theme or pathway. We compute correlations between different gene set tests and elect to use Fisher's self-contained method for gene set analysis...
2016: PloS One
Nameeta P Richard, Raffaella Pippa, Megan M Cleary, Alka Puri, Deanne Tibbitts, Shawn Mahmood, Dale J Christensen, Sophia Jeng, Shannon McWeeney, A Thomas Look, Bill H Chang, Jeffrey W Tyner, Michael P Vitek, María D Odero, Rosalie Sears, Anupriya Agarwal
Recent evidence suggests that inhibition of protein phosphatase 2A (PP2A) tumor suppressor activity via the SET oncoprotein contributes to the pathogenesis of various cancers. Here we demonstrate that both SET and c-MYC expression are frequently elevated in T-ALL cell lines and primary samples compared to healthy T cells. Treatment of T-ALL cells with the SET antagonist OP449 restored the activity of PP2A and reduced SET interaction with the PP2A catalytic subunit, resulting in a decrease in cell viability and c-MYC expression in a dose-dependent manner...
October 1, 2016: Oncotarget
Guo-Hua Zhang, Tao Wu, Faizan A Sadiq, Huan-Yi Yang, Tong-Jie Liu, Hui Ruan, Guo-Qing He
Aroma of Chinese steamed bread (CSB) is one of the important parameters that determines the overall quality attributes and consumer acceptance. However, the aroma profile of CSB still remains poorly understood, mainly because of relying on only a single method for aroma extraction in previous studies. Therefore, the objective of this study was to determine the volatile aroma compounds of five different samples of CSB using three different aroma extraction methods, namely solid-phase microextraction (SPME), simultaneous distillation-extraction (SDE), and purge and trap (P&T)...
2016: Journal of Zhejiang University. Science. B
Lisa M Greene, Seema M Nathwani, Daniela M Zisterer
T-cell acute lymphoblastic leukemia (T-ALL) is a rare and aggressive hematopoietic malignancy prone to relapse and drug resistance. Half of all T-ALL patients exhibit mutations in Notch1, which leads to aberrant Notch1 associated signaling cascades. Notch1 activation is mediated by the γ-secretase cleavage of the Notch1 receptor into the active intracellular domain of Notch1 (NCID). Clinical trials of γ-secretase small molecule inhibitors (GSIs) as single agents for the treatment of T-ALL have been unsuccessful...
October 2016: Oncology Letters
Zheng Ge, Min Li, Gang Zhao, Lichan Xiao, Yan Gu, Xilian Zhou, Michael D Yu, Jianyong Li, Sinisa Dovat, Chunhua Song
Genetic mutations on signaling pathways are found in patients with T-cell acute lymphoblastic leukemia (T-ALL) and act as markers of high-risk leukemia. Mutations in dynamin 2 (DNM2) have been reported in T-ALL, particularly in early T-cell precursor-ALL. In the present study, DNM2 mutations were screened by sequencing DNM2 exons obtained by polymerase chain reaction amplification and gel purification in adult T-ALL patients. A total of 4 novel DNM2 mutations were identified in adult T-ALL patients, with a mutation rate of 9...
October 2016: Oncology Letters
S R Oruganti, D J Torres, S Krebsbach, F Asperti-Boursin, J Winters, K Matlawska-Wasowska, S S Winter, C Halsey, J L Cannon
No abstract text is available yet for this article.
October 21, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Antonis Dagklis, Sofie Demeyer, Jolien De Bie, Enrico Radaelli, Daphnie Pauwels, Sandrine Degryse, Olga Gielen, Carmen Vicente, Roel Vandepoel, Ellen Geerdens, Anne Uyttebroeck, Nancy Boeckx, Charles E de Bock, Jan Cools
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive childhood leukemia that is caused by the accumulation of multiple genomic lesions resulting in transcriptional deregulation and increased cell proliferation and survival. Through analysis of gene expression data, we provide evidence that the hedgehog pathway is activated in 20% of T-ALL samples. Hedgehog pathway activation is associated with ectopic expression of the hedgehog ligands SHH or IHH, and with upregulation of the transcription factor GLI1...
September 30, 2016: Blood
Haluk Yuzugullu, Thanh Von, Lauren M Thorpe, Sarah R Walker, Thomas M Roberts, David A Frank, Jean J Zhao
Loss of PTEN, a negative regulator of the phosphoinositide 3-kinase signaling pathway, is a frequent event in T-cell acute lymphoblastic leukemia, suggesting the importance of phosphoinositide 3-kinase activity in this disease. Indeed, hyperactivation of the phosphoinositide 3-kinase pathway is associated with the disease aggressiveness, poor prognosis and resistance to current therapies. To identify a molecular pathway capable of cooperating with PTEN deficiency to drive oncogenic transformation of leukocytes, we performed an unbiased transformation screen with a library of tyrosine kinases...
2016: Cell Discovery
Mark Y Chiang, Qing Wang, Anna C Gormley, Sarah J Stein, Lanwei Xu, Olga Shestova, Jon C Aster, Warren S Pear
Activating NOTCH1 mutations are frequent in human T-cell acute lymphoblastic leukemia (T-ALL) and Notch inhibitors (gamma-secretase inhibitors or GSI) have produced responses in patients with relapsed, refractory disease. However, sustained responses, while reported, are uncommon, suggesting other pathways can substitute for Notch in T-ALL. To address this possibility, we first generated Kras(G12D) transgenic mice with T-cell specific expression of the pan-Notch inhibitor, DNMAML. These mice developed leukemia, but instead of accessing alternative oncogenic pathways, the tumor cells acquired Notch1 mutations and subsequently deleted DNMAML, reinforcing the notion that activated Notch1 is particularly transforming within the context of T-cell progenitors...
September 26, 2016: Blood
Lu Qian, Wanggang Zhang, Bo Lei, Aili He, Lianhong Ye, Xingzhou Li, Xin Dong
The present study aimed to investigate the role of microRNA (miR)-101 in acute lymphoblastic leukemia progression and chemoresistance. Furthermore, a novel target gene of miR-101 was identified. Here, we confirmed that miR-101 was significantly downregulated in the blood samples of patients with T-cell acute lymphoblastic leukemia (T-ALL) compared with the healthy controls, as determined by reverse transcription quantitative polymerase chain reaction (RTqPCR) analysis. The in vitro experiments demonstrated that miR-101 significantly repressed the proliferation and invasion, and induced potent apoptosis in Jurkat cells, as determined by CCK-8, flow cytometer and cell invasion assays...
September 21, 2016: Oncology Reports
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