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https://www.readbyqxmd.com/read/29666622/chemotactic-cues-for-notch1-dependent-leukemia
#1
REVIEW
Erich Piovan, Valeria Tosello, Alberto Amadori, Paola Zanovello
The NOTCH signaling pathway is a conserved signaling cascade that regulates many aspects of development and homeostasis in multiple organ systems. Aberrant activity of this signaling pathway is linked to the initiation and progression of several hematological malignancies, exemplified by T-cell acute lymphoblastic leukemia (T-ALL). Interestingly, frequent non-mutational activation of NOTCH1 signaling has recently been demonstrated in B-cell chronic lymphocytic leukemia (B-CLL), significantly extending the pathogenic significance of this pathway in B-CLL...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29665899/-statins-regulate-the-proliferation-and-apoptosis-of-t-all-cells-through-the-inhibition-of-akt-pathway
#2
Jun-Jie Wang, Yu Tian, Kai-Lin Xu, Rui-Xue Fu, Ming-Shan Niu, Kai Zhao
OBJECTIVE: To investigate the effect of Statins on proliferation and apoptosis in human acute T lymphocytic leukemia (T-ALL) cells and its possible mechanism. METHODS: Jurkat and CCRF-CEM cells were cultured in different concentrations of Fluvastatin and Simvastatin for 24 h respectively. Then, the cell growth inhibition level was defected by CCK-8; the DNA replication was analyzed by EdU; the cell apoptosis was analyzed by Annexin V/7-AAD double labeling; the cell cycle changes were analyzed by flow cytometry; the expressions of Cyclin D1, p21, p27, BAX, BCL-2 and p-Akt were determined by Western blot...
April 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29662863/investigation-of-bax-and-bcl2-expression-and-apoptosis-in-a-resveratrol-and-prednisolone-treated-human-t-all-cell-line-ccrf-cem
#3
Taghi Khanzadeh, Majid Farshdousti Hagh, Mehdi Talebi, Bahman Yousefi, Ako Azimi, Abbas Ali Hossein Pour Feizi, Behzad Baradaran
Background: The numerous side effects and chemo-resistance of conventional chemical drugs in the treatment of malignancies have led to consideration of the anti-cancer properties of natural products. In the present study, we aimed to explore the apoptotic effect of two natural components, resveratrol and prednisolone, on the T acute lymphoblastic leukemia (ALL) cell line, CCRF-CEM. Our findings suggested the incorporation of these natural agents into drug regimens to treat patients with ALL...
March 2018: Blood Research
https://www.readbyqxmd.com/read/29643474/histone-deacetylase-6-controls-notch3-trafficking-and-degradation-in-t-cell-acute-lymphoblastic-leukemia-cells
#4
Marica Pinazza, Margherita Ghisi, Sonia Minuzzo, Valentina Agnusdei, Gianluca Fossati, Vincenzo Ciminale, Laura Pezzè, Yari Ciribilli, Giorgia Pilotto, Carolina Venturoli, Alberto Amadori, Stefano Indraccolo
Several studies have revealed that endosomal sorting controls the steady-state levels of Notch at the cell surface in normal cells and prevents its inappropriate activation in the absence of ligands. However, whether this highly dynamic physiologic process can be exploited to counteract dysregulated Notch signaling in cancer cells remains unknown. T-ALL is a malignancy characterized by aberrant Notch signaling, sustained by activating mutations in Notch1 as well as overexpression of Notch3, a Notch paralog physiologically subjected to lysosome-dependent degradation in human cancer cells...
April 12, 2018: Oncogene
https://www.readbyqxmd.com/read/29643030/-screening-and-verification-of-key-genes-in-t-cell-acute-lymphoblastic-leukemia
#5
Guang-Jie Jiang, Yan-Hua Chen, Wei Guo, Hang Zhang, Lin Zou
OBJECTIVE: To explore the key genes in T-cell acute lymphoblastic leukemia (T-ALL) using bioinformatics method to better understand the pathogenic mechanisms of T-ALL. METHODS: The gene expression profiles of GSE14317 were obtained from Gene Expression Omnibus database. The differentially expressed genes (DEGs) in T-ALL were analyzed using R package Limma. The online analysis tool DAVID was used to perform the functional and pathway enrichment analysis. The protein-protein interaction network was constructed by STRING and visualized by Cytoscape...
March 20, 2018: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/29642663/association-of-leptin-tlr4-and-cxcr1-snps-with-fertility-traits-in-czech-fleckvieh-cattle
#6
Katerina Jecminkova, Uwe Müller, Jitka Kyselova, Zuzana Sztankoova, Ludmila Zavadilova, Miloslava Stipkova, Ivan Majzlik
Objective: The use of genetic markers can help to enhance reproduction in cattle, which is a very important trait for profitability in dairy production systems. This study evaluated the association between genotypes of Leptin (LEP), Toll-like receptor 4 (TLR4), and Chemokine receptor of interleukin 8 C-X-C motif (CXCR1) genes and fertility traits in Czech Fleckvieh cattle. Methods: Phenotypic data from 786 Czech Fleckvieh cows raised on 5 farms in the Czech Republic were used, along with information from the 1st three parities...
April 12, 2018: Asian-Australasian Journal of Animal Sciences
https://www.readbyqxmd.com/read/29642462/new-challenges-in-targeting-signaling-pathways-in-acute-lymphoblastic-leukemia-by-ngs-approaches-an-update
#7
REVIEW
Adrián Montaño, Maribel Forero-Castro, Darnel Marchena-Mendoza, Rocío Benito, Jesús María Hernández-Rivas
The identification and study of genetic alterations involved in various signaling pathways associated with the pathogenesis of acute lymphoblastic leukemia (ALL) and the application of recent next-generation sequencing (NGS) in the identification of these lesions not only broaden our understanding of the involvement of various genetic alterations in the pathogenesis of the disease but also identify new therapeutic targets for future clinical trials. The present review describes the main deletions, amplifications, sequence mutations, epigenetic lesions, and new structural DNA rearrangements detected by NGS in B-ALL and T-ALL and their clinical importance for therapeutic procedures...
April 7, 2018: Cancers
https://www.readbyqxmd.com/read/29629541/clinical-and-pathologic-findings-of-korean-patients-with-ryr1-related-congenital-myopathy
#8
Ha Neul Jeong, Hyung Jun Park, Jung Hwan Lee, Ha Young Shin, Se Hoon Kim, Seung Min Kim, Young Chul Choi
BACKGROUND AND PURPOSE: This study was designed to investigate clinical and pathologic characteristics of five Korean patients with RYR1-related congenital myopathy (CM). METHODS: Five patients from unrelated families were diagnosed with RYR1-related CM via direct or targeted sequencing of RYR1. Their clinical, mutational, and pathologic findings were then analyzed. RESULTS: Seven different mutations were identified, including two novel mutations: c...
January 2018: Journal of Clinical Neurology
https://www.readbyqxmd.com/read/29589281/treatment-outcome-of-children-with-acute-lymphoblastic-leukemia-the-tokyo-children-s-cancer-study-group-tccsg-study-l04-16
#9
Hiroyuki Takahashi, Ryosuke Kajiwara, Motohiro Kato, Daisuke Hasegawa, Daisuke Tomizawa, Yasushi Noguchi, Kazutoshi Koike, Daisuke Toyama, Hiromasa Yabe, Michiko Kajiwara, Junya Fujimura, Manabu Sotomatsu, Setsuo Ota, Miho Maeda, Hiroaki Goto, Yoko Kato, Tetsuya Mori, Takeshi Inukai, Hiroyuki Shimada, Keitaro Fukushima, Chitose Ogawa, Atsushi Makimoto, Takashi Fukushima, Kentaro Ohki, Katsuyoshi Koh, Nobutaka Kiyokawa, Atsushi Manabe, Akira Ohara
The survival rate of children with acute lymphoblastic leukemia (ALL) has increased to approximately 90% after substantial progress in risk-oriented treatment strategies. Between 2005 and 2013, the Tokyo Children's Cancer Study Group (TCCSG) conducted a risk-oriented, non-randomized study, L04-16. The principal aim of this study was to assemble background characteristics and treatment outcomes, and gather genetic information on leukemic cells under central diagnosis. This report outlines the background characteristics and treatment outcomes of 1033 children with ALL treated according to a TCCSG platform...
March 27, 2018: International Journal of Hematology
https://www.readbyqxmd.com/read/29575419/forty-nine-cases-of-acute-lymphoblastic-leukaemia-lymphoma-in-pleural-and-pericardial-effusions-a-cytological-histological-correlation
#10
J Li, W Zhang, W Wang, Y Jiang, S Zhao, W Liu, G Li, N Liu, Q Li, X Su
INTRODUCTION: Acute lymphoblastic leukaemia/lymphoma (ALL/LBL) is an aggressive entity of precursor lymphoid neoplasm and may cause malignant serous effusion (SE). The current study aimed to analyse the characteristics of SE cytology of ALL/LBL including cytomorphology, immunophenotyping, clonality and evaluate the effectiveness of SE cytology as a diagnostic method for ALL/LBL. METHODS: SE specimens with final diagnosis of ALL/LBL from 2006 to 2016 were reviewed for clinical data, cytomorphological features and ancillary studies...
April 2018: Cytopathology: Official Journal of the British Society for Clinical Cytology
https://www.readbyqxmd.com/read/29574603/nationwide-survey-of-therapy-related-leukemia-in-childhood-in-japan
#11
Toshihiko Imamura, Takashi Taga, Masatoshi Takagi, Hirohide Kawasaki, Katsuyoshi Koh, Tomohiko Taki, Souichi Adachi, Atsushi Manabe, Yasushi Ishida
Therapy-related leukemia (t-leukemia) is associated with dismal prognosis. Published pediatric t-leukemia data are somewhat outdated and may not reflect recent advances in treatment. We report a retrospective nationwide survey of patients diagnosed between 2000 and 2013 in Japan. We identified 43 patients with pediatric t-leukemia; 33 had t-acute myeloid leukemia (t-AML), eight had t-acute lymphoblastic leukemia (t-ALL) and two had t-acute undifferentiated leukemia. Median age at onset and latency were 12 years and 3...
March 24, 2018: International Journal of Hematology
https://www.readbyqxmd.com/read/29556024/the-subclonal-complexity-of-stil-tal1-t-cell-acute-lymphoblastic-leukaemia
#12
Caroline L Furness, Marcela B Mansur, Victoria J Weston, Luca Ermini, Frederik W van Delft, Sarah Jenkinson, Rosemary Gale, Christine J Harrison, Maria S Pombo-de-Oliveira, Marta Sanchez-Martin, Adolfo A Ferrando, Pamela Kearns, Ian Titley, Anthony M Ford, Nicola E Potter, Mel Greaves
Single-cell genetics were used to interrogate clonal complexity and the sequence of mutational events in STIL-TAL1+ T-ALL. Single-cell multicolour FISH was used to demonstrate that the earliest detectable leukaemia subclone contained the STIL-TAL1 fusion and copy number loss of 9p21.3 (CDKN2A/CDKN2B locus), with other copy number alterations including loss of PTEN occurring as secondary subclonal events. In three cases, multiplex qPCR and phylogenetic analysis were used to produce branching evolutionary trees recapitulating the snapshot history of T-ALL evolution in this leukaemia subtype, which confirmed that mutations in key T-ALL drivers, including NOTCH1 and PTEN, were subclonal and reiterative in distinct subclones...
March 20, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29535432/saracatinib-impairs-maintenance-of-human-t-all-by-targeting-the-lck-tyrosine-kinase-in-cells-displaying-high-level-of-lipid-rafts
#13
Anne Buffière, Théo Accogli, Laetitia Saint-Paul, Géraldine Lucchi, Benjamin Uzan, Paola Ballerini, Jean-Noël Bastie, Laurent Delva, Françoise Pflumio, Ronan Quéré
No abstract text is available yet for this article.
February 28, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29527929/notch-signaling-as-a-therapeutic-target-for-acute-lymphoblastic-leukemia
#14
Diana Bellavia, Rocco Palermo, Maria Pia Felli, Isabella Screpanti, Saula Checquolo
Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. Although the therapy of ALL has significantly improved, the heterogeneous genetic landscape of the disease often causes relapse, which is difficult to treat. Achieving a positive outcome for patients with relapsed or refractory ALL remains a challenging issue. The high prevalence of NOTCH-activating mutations in T-cell acute lymphoblastic leukemia (T-ALL) and the central role of NOTCH signaling in regulating cell survival and growth of ALL provide a rationale for the development of Notch signaling-targeted strategies in this disease...
March 12, 2018: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29516189/dft-study-of-geometrical-and-vibrational-features-of-a-3-5-deoxydisugar-monophosphate-ddsmp-dna-model-in-the-presence-of-counterions-and-solvent
#15
Alain Minguirbara, Mama Nsangou
The B3LYP/6-31++G* theoretical level was used to study the influence of various hexahydrated monovalent (Li+ , Na+ , K+ ) and divalent (Mg2+ ) metal counterions in interaction with the charged PO2 - group, on the geometrical and vibrational characteristics of the DNA fragments of 3',5'-dDSMP, represented by four conformers (g+ g+ , g+ t, g- g- and g- t). All complexes were optimized through two solvation models [the explicit model (6H2 O) and the hybrid model (6H2 O/Continuum)]. The results obtained established that, in the hybrid model, counterions (Li+ , Na+ , K+ , Mg2+ ) always remain in the bisector plane of the O1-P-O2 angle...
March 7, 2018: Journal of Molecular Modeling
https://www.readbyqxmd.com/read/29515258/akr1c-enzymes-sustain-therapy-resistance-in-paediatric-t-all
#16
Roberta Bortolozzi, Silvia Bresolin, Elena Rampazzo, Maddalena Paganin, Francesca Maule, Elena Mariotto, Daniele Boso, Sonia Minuzzo, Valentina Agnusdei, Giampietro Viola, Geertruy Te Kronnie, Giovanni Cazzaniga, Giuseppe Basso, Luca Persano
BACKGROUND: Despite chemotherapy intensification, a subgroup of high-risk paediatric T-cell acute lymphoblastic leukemia (T-ALL) patients still experience treatment failure. In this context, we hypothesised that therapy resistance in T-ALL might involve aldo-keto reductase 1C (AKR1C) enzymes as previously reported for solid tumors. METHODS: Expression of NRF2-AKR1C signaling components has been analysed in paediatric T-ALL samples endowed with different treatment outcomes as well as in patient-derived xenografts of T-ALL...
March 8, 2018: British Journal of Cancer
https://www.readbyqxmd.com/read/29496700/-dar-ing-to-target-cd38-in-t-all
#17
Joseph Wynne, Wendy Stock
No abstract text is available yet for this article.
March 1, 2018: Blood
https://www.readbyqxmd.com/read/29496689/characterization-of-camptothecin-induced-genomic-changes-in-the-camptothecin-resistant-t-all-derived-cell-line-cpt-k5
#18
Eigil Kjeldsen, Christine J F Nielsen, Amit Roy, Cinzia Tesauro, Ann-Katrine Jakobsen, Magnus Stougaard, Birgitta R Knudsen
Acquisition of resistance to topoisomerase I (TOP1)-targeting camptothecin (CPT) derivatives is a major clinical problem. Little is known about the underlying chromosomal and genomic mechanisms. We characterized the CPT-K5 cell line expressing mutant CPT-resistant TOP1 and its parental T-cell derived acute lymphoblastic leukemia CPT-sensitive RPMI-8402 cell line by karyotyping and molecular genetic methods, including subtractive oligo-based array comparative genomic hybridization (soaCGH) analysis. Karyotyping revealed that CPT-K5 cells had acquired additional structural aberrations and a reduced modal chromosomal number compared to RPMI-8402...
March 2018: Cancer Genomics & Proteomics
https://www.readbyqxmd.com/read/29483708/an-off-the-shelf-fratricide-resistant-car-t-for-the-treatment-of-t-cell-hematologic-malignancies
#19
Matthew L Cooper, Jaebok Choi, Karl Staser, Julie K Ritchey, Jessica M Devenport, Kayla Eckardt, Michael P Rettig, Bing Wang, Linda G Eissenberg, Armin Ghobadi, Leah N Gehrs, Julie L Prior, Samuel Achilefu, Christopher A Miller, Catrina C Fronick, Julie O'Neal, Feng Gao, David M Weinstock, Alejandro Gutierrez, Robert S Fulton, John F DiPersio
T cell malignancies represent a group of hematologic cancers with high rates of relapse and mortality in patients for whom no effective targeted therapies exist. The shared expression of target antigens between chimeric antigen receptor (CAR) T cells and malignant T cells has limited the development of CAR-T because of unintended CAR-T fratricide and an inability to harvest sufficient autologous T cells. Here, we describe a fratricide-resistant "off-the-shelf" CAR-T (or UCART7) that targets CD7+ T cell malignancies and, through CRISPR/Cas9 gene editing, lacks both CD7 and T cell receptor alpha chain (TRAC) expression...
February 20, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29472723/flow-cytometric-vs-morphologic-assessment-of-remission-in-childhood-acute-lymphoblastic-leukemia-a-report-from-the-children-s-oncology-group-cog
#20
Sumit Gupta, Meenakshi Devidas, Mignon L Loh, Elizabeth A Raetz, Si Chen, Cindy Wang, Patrick Brown, Andrew J Carroll, Nyla A Heerema, Julie M Gastier-Foster, Kimberly P Dunsmore, Eric C Larsen, Kelly W Maloney, Leonard A Mattano, Stuart S Winter, Naomi J Winick, William L Carroll, Stephen P Hunger, Michael J Borowitz, Brent L Wood
Minimal residual disease (MRD) after initial therapy is integral to risk stratification in B-precursor and T-precursor acute lymphoblastic leukemia (B-ALL, T-ALL). Although MRD determines depth of remission, remission remains defined by morphology. We determined the outcomes of children with discordant assessments of remission by morphology vs. flow cytometry using patients age 1-30.99 years enrolled on Children's Oncology Group ALL trials who underwent bone marrow assessment at the end of induction (N = 9350)...
February 23, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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