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Fabrizio Rossi, Camille Stephan-Otto Attolini, Jose Luis Mosquera, Cayetano Gonzalez
Single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) are found at different rates in human cancer. To determine if these genetic lesions appear in Drosophila tumours we have sequenced the genomes of 17 malignant neoplasms caused by mutations in l(3)mbt, brat, aurA , or lgl We have found CNVs and SNPs in all the tumours. Tumour-linked CNVs range between 11 and 80 per sample, affecting between 92 and 1546 coding sequences. CNVs are in average less frequent in l(3)mbt than in brat lines. Nearly half of the CNVs fall within the 10 to 100Kb range, all tumour samples contain CNVs larger that 100 Kb and some have CNVs larger than 1Mb...
February 21, 2018: G3: Genes—Genomes—Genetics
Nahid Shahmarvand, Alexandra Nagy, Jahanbanoo Shahryari, Robert S Ohgami
In recent years, it has become clear that members of the signal transducer and activator of transcription (STAT) family of genes play an important role in cancer. The STAT family consists of six genes, STAT1-4, STAT5A/ STAT5B and STAT6, that are involved in regulating cellular proliferation, apoptosis, angiogenesis and the immune system response. Constitutive activation of STAT3, via mutational changes, has been shown to be important in oncogenesis in both solid and hematopoietic cancers. In the case of hematopoietic neoplasms, STAT3 driver mutations have been described in T-cell large granular lymphocytic leukemia (T-LGL) and chronic natural killer lymphoproliferative disorders (CLPD-NK) and are seen in 30-40% of T-LGL patients...
February 8, 2018: Cancer Science
Rebecca Stephens, Krystle Lim, Marta Portela, Marc Kvansakul, Patrick O Humbert, Helena E Richardson
The Scribble cell polarity module, comprising Scribbled (Scrib), Discs-large (Dlg) and Lethal-2-giant larvae (Lgl), has a tumor suppressive role in mammalian epithelial cancers. The Scribble module proteins play key functions in the establishment and maintenance of different modes of cell polarity, as well as in the control of tissue growth, differentiation and directed cell migration, and therefore are major regulators of tissue development and homeostasis. Whilst molecular details are known regarding the roles of Scribble module proteins in cell polarity regulation, their precise mode of action in the regulation of other key cellular processes remains enigmatic...
January 30, 2018: Journal of Molecular Biology
Tanu Goyal, Beenu Thakral, Sa A Wang, Carlos E Bueso-Ramos, Min Shi, Dragan Jevremovic, William G Morice, Qian-Yun Zhang, Tracy I George, Kathryn K Foucar, Siddharth Bhattacharyya, Adam Bagg, Heesun J Rogers, Juraj Bodo, Lisa Durkin, Eric D Hsi
Objective: T-cell large granular lymphocytic (T-LGL) leukemia is associated with B-cell lymphomas (BCLs), especially small BCLs. We aimed to explore and expand upon its association with BCLs. Methods: We retrospectively studied clinicopathologic features of T-LGL leukemia patients with coexisting BCL from January 2001 to December 2016. Results: Among 432 patients with T-LGL leukemia, 22 (5.1%) had an associated B-cell non-Hodgkin lymphoma...
January 20, 2018: American Journal of Clinical Pathology
Scott G Daniel, Atlantis D Russ, Kathryn M Guthridge, Ammad I Raina, Patricia S Estes, Linda M Parsons, Helena E Richardson, Joyce A Schroeder, Daniela C Zarnescu
Drosophila lethal giant larvae (lgl) encodes a conserved tumor suppressor with established roles in cell polarity, asymmetric division, and proliferation control. Lgl's human orthologs, HUGL1 and HUGL2, are altered in human cancers, however, its mechanistic role as a tumor suppressor remains poorly understood. Based on a previously established connection between Lgl and Fragile X protein (FMRP), a miRNA associated translational regulator, we hypothesized that Lgl may exert its role as a tumor suppressor by interacting with the miRNA pathway...
December 20, 2017: Biology Open
Zhiqiang Shu, Yi-Chun Huang, William H Palmer, Yoichiro Tamori, Gengqiang Xie, Hui Wang, Nan Liu, Wu-Min Deng
Despite their emergence as an important class of noncoding RNAs involved in cancer cell transformation, invasion, and migration, the precise role of microRNAs (miRNAs) in tumorigenesis remains elusive. To gain insights into how miRNAs contribute to primary tumor formation, we conducted an RNA sequencing (RNA-Seq) analysis of Drosophila wing disc epithelial tumors induced by knockdown of a neoplastic tumor-suppressor gene (nTSG) lethal giant larvae (lgl), combined with overexpression of an active form of oncogene Ras (RasV12 ), and identified 51 mature miRNAs that changed significantly in tumorous discs...
December 12, 2017: Oncotarget
Amin T Turki, Jassin Rashidi-Alavijeh, Jan Dürig, Guido Gerken, Peter-Michael Rath, Oliver Witzke
BACKGROUND: Invasive aspergillosis involving patients with neutropenia or severe immunosuppression, such as patients with hematologic malignancies is associated with high mortality. Patients with T-cell large granular lymphocytic leukemia (T-LGL) on the other hand are considered to be less vulnerable for severe opportunistic fungal infection as their course of disease is chronic and marked by less violent cytopenia then in e.g. Aplastic Anemia. Only neutropenia is regarded as independent risk factor for severe opportunistic infection in T-LGL patients...
December 28, 2017: BMC Infectious Diseases
Chen-Yuan Tseng, Hwei-Jan Hsu
Snail, a zinc-finger transcription factor, controls the process of epithelial-mesenchymal transition, and ectopic expression of this protein may produce cells with stem cell properties. Because the effect of Snail expression in ovarian epithelial cells remains unclear, we generated Drosophila ovarian follicle stem cells (FSCs) with homozygous Scutoid (Sco) mutation. The Sco mutation is a reciprocal transposition that is known to induce ectopic Snail activity. We found that Sco mutant FSCs showed excess proliferation and high competitiveness for niche occupancy, and the descendants of this lineage formed outgrowths that failed to enter the endocycle...
2017: PloS One
Heikki Kuusanmäki, Olli Dufva, Elina Parri, Arjan J van Adrichem, Hanna Rajala, Muntasir M Majumder, Bhagwan Yadav, Alun Parsons, Wing C Chan, Krister Wennerberg, Satu Mustjoki, Caroline A Heckman
Constitutive JAK/STAT3 signaling contributes to disease progression in many lymphoproliferative disorders. Recent genetic analyses have revealed gain-of-function STAT3 mutations in lymphoid cancers leading to hyperactivation of STAT3, which may represent a potential therapeutic target. Using a functional reporter assay, we screened 306 compounds with selective activity against various target molecules to identify drugs capable of inhibiting the cellular activity of STAT3. Top hits were further validated with additional models including STAT3-mutated natural killer (NK)-cell leukemia/lymphoma cell lines and primary large granular lymphocytic (LGL) leukemia cells to assess their ability to inhibit STAT3 phosphorylation and STAT3 dependent cell viability...
November 14, 2017: Oncotarget
Tal Gazitt, Thomas P Loughran
This section reviews the diagnostic criteria and pathogenesis of large granular lymphocyte (LGL) leukemia. There is a particular focus on the overlap of LGL leukemia and rheumatoid arthritis (Felty's syndrome). Current understanding of the mechanisms of neutropenia in these disorders is discussed. Finally, treatment indications and therapeutic recommendations are outlined.
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
Emma I Andersson, Alessandro Coppe, Stefania Bortoluzzi
No abstract text is available yet for this article.
November 7, 2017: Oncotarget
Michal Milgrom-Hoffman, Patrick O Humbert
Since the first identification of the Scribble polarity module proteins as a new class of tumour suppressors that regulate both cell polarity and proliferation, an increasing amount of evidence has uncovered a broader role for Scribble, Dlg and Lgl in the control of fundamental cellular functions and their signalling pathways. Here, we review these findings as well as discuss more specifically the role of the Scribble module in PCP signalling.
November 22, 2017: Seminars in Cell & Developmental Biology
Ram Prakash Gupta, Anjali Bajpai, Pradip Sinha
During animal development, selector genes determine identities of body segments and those of individual organs. Selector genes are also misexpressed in cancers, although their contributions to tumor progression per se remain poorly understood. Using a model of cooperative tumorigenesis, we show that gain of selector genes results in tumor cooperation, but in only select developmental domains of the wing, haltere and eye-antennal imaginal discs of Drosophila larva. Thus, the field selector, Eyeless (Ey), and the segment selector, Ultrabithorax (Ubx), readily cooperate to bring about neoplastic transformation of cells displaying somatic loss of the tumor suppressor, Lgl, but in only those developmental domains that express the homeo-box protein, Homothorax (Hth), and/or the Zinc-finger protein, Teashirt (Tsh)...
November 15, 2017: Biology Open
Zhi-Yuan Qiu, Guang-Yu Tian, Zhao Zhang, Ye-Qing Zhang, Wei Xu, Jian-Yong Li
Post-transplant lymphoproliferative disorders (PTLD) represent a heterogeneous group of diseases that occur following transplantation. Large granular lymphocytic (LGL) lymphocytosis is one type of PTLD, ranging from reactive polyclonal self-limited expansion to oligo/monoclonal lymphocytosis or even to overt leukaemia. LGL lymphocytosis in transplant recipients may present as a relatively indolent version of the condition and may be more common than reported, but its natural history and clinical course have not been well described, and the lack of a reliable classification system has limited studies on this disease...
October 6, 2017: Oncotarget
Takashi Kumagai, Chiaki Nakaseko, Kaichi Nishiwaki, Chikashi Yoshida, Kazuteru Ohashi, Naoki Takezako, Hina Takano, Yasuji Kouzai, Tadashi Murase, Kosei Matsue, Satoshi Morita, Junichi Sakamoto, Hisashi Wakita, Hisashi Sakamaki, Koiti Inokuchi
Tyrosine kinase inhibitors (TKI) improve the prognosis of patients with chronic myelogenous leukemia (CML) by inducing substantial deep molecular responses (DMR); some patients have successfully discontinued TKI therapy after maintaining DMR for ≥1 year. In this cessation study, we investigated the optimal conditions for dasatinib discontinuation in patients who maintained DMR for ≥2 years. This study included 54 patients with CML who were enrolled in a D-STOP multicenter prospective trial, had achieved DMR, and had discontinued dasatinib after 2-year consolidation...
January 2018: Cancer Science
Antonella Teramo, Gregorio Barilà, Giulia Calabretto, Chiara Ercolin, Thierry Lamy, Aline Moignet, Mikael Roussel, Cédric Pastoret, Matteo Leoncin, Cristina Gattazzo, Anna Cabrelle, Elisa Boscaro, Sara Teolato, Elisa Pagnin, Tamara Berno, Elena De March, Monica Facco, Francesco Piazza, Livio Trentin, Gianpietro Semenzato, Renato Zambello
STAT3 mutations have been described in 30-40% of T-large granular lymphocyte (T-LGL) leukemia patients, leading to STAT3 pathway activation. Considering the heterogeneity of the disease and the several immunophenotypes that LGL clone may express, the aim of this work was to evaluate whether STAT3 mutations might be associated with a distinctive LGL immunophenotype and/or might be indicative for specific clinical features. Our series of cases included a pilot cohort of 101 T-LGL leukemia patients (68 CD8+/CD4- and 33 CD4+/CD8±) from Padua Hematology Unit (Italy) and a validation cohort of additional 20 patients from Rennes Hematology Unit (France)...
September 22, 2017: Oncotarget
Hai-Fang Zhang, Zhen-Dong Huang, Xue-Run Wu, Qian Li, Zhi-Feng Yu
AIMS: This study aims to compare the proportion of peripheral blood T lymphocyte subsets and related blood cell and bone marrow cytology indexes between patients with aplastic anemia (AA) and hypoplastic myelodysplastic syndrome (hypo-MDS), and investigate the clinical identification significance. MATERIALS AND METHODS: A total of 41 patients with AA and 46 patients with hypo-MDS were collected, and the proportions of peripheral blood T lymphocyte subsets, CD3(-)CD16/CD56(+)NK cells, CD3(+)CD57(+)T-LGL cells and CD19(+)B lymphocytes were detected by flow cytometry...
November 15, 2017: Life Sciences
Chengwei Wang, Yunhui Gong, Jiaqi Dai, Lei Zhang, Hua Xie, Glenn Pastel, Boyang Liu, Eric Wachsman, Howard Wang, Liangbing Hu
The garnet-based solid state electrolyte (SSE) is considered a promising candidate to realize all solid state lithium (Li) metal batteries. However, critical issues require additional investigation before practical applications become possible, among which high interfacial impedance and low interfacial stability remain the most challenging. In this work, neutron depth profiling (NDP), a nondestructive and uniquely Li-sensitive technique, has been used to reveal the interfacial behavior of garnet SSE in contact with metallic Li through in situ monitoring of Li plating-stripping processes...
October 11, 2017: Journal of the American Chemical Society
Christopher Bragg, Ben Desbrow, Susan Hall, Christopher Irwin
OBJECTIVE: Monotonous driving involves low levels of stimulation and high levels of repetition and is essentially an exercise in sustained attention and vigilance. The aim of this study was to determine the effects of consuming a high or low glycemic load meal on prolonged monotonous driving performance. The effect of consuming caffeine with a high glycemic load meal was also examined. METHOD: Ten healthy, non-diabetic participants (7 males, age 51±7yrs, mean±SD) completed a repeated measures investigation involving 3 experimental trials...
November 1, 2017: Physiology & Behavior
Uroosa Ibrahim, Sara Parylo, Shiksha Kedia, Shafinaz Hussein, Jean Paul Atallah
Large granular lymphocytic (LGL) leukemia is a rare form of low grade leukemia characterized by large cytotoxic T cells or natural killer cells on morphological examination. Immunosuppressive therapy is employed as first-line therapy. Treatment options in refractory cases include the anti-CD52 antibody alemtuzumab and purine analogues. We report a rare case that responded to the anti-CD20 monoclonal antibody rituximab. A 77-year-old female presented with complaints of fatigue, fever, and chills of 3 months' duration...
2017: Case Reports in Hematology
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