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https://www.readbyqxmd.com/read/28054750/somatic-med12-nonsense-mutation-escapes-mrna-decay-and-reveals-a-motif-required-for-nuclear-entry
#1
Tuomas Heikkinen, Kati Kämpjärvi, Salla Keskitalo, Pernilla von Nandelstadh, Xiaonan Liu, Ville Rantanen, Esa Pitkänen, Matias Kinnunen, Heikki Kuusanmäki, Mika Kontro, Mikko Turunen, Netta Mäkinen, Jussi Taipale, Caroline Heckman, Kaisa Lehti, Satu Mustjoki, Markku Varjosalo, Pia Vahteristo
MED12 is a key component of the transcription-regulating Mediator complex. Specific missense and in-frame insertion/deletion mutations in exons 1 and 2 have been identified in uterine leiomyomas, breast tumors, and chronic lymphocytic leukemia. Here, we characterize the first MED12 5' end nonsense mutation (c.97G>T, p.E33X) identified in acute lymphoblastic leukemia and show that it escapes nonsense-mediated mRNA decay (NMD) by using an alternative translation initiation site. The resulting N-terminally truncated protein is unable to enter the nucleus due to the lack of identified nuclear localization signal (NLS)...
January 5, 2017: Human Mutation
https://www.readbyqxmd.com/read/28053192/mature-cd10-and-immature-cd10-neutrophils-present-in-g-csf-treated-donors-display-opposite-effects-on-t-cells
#2
Olivia Marini, Sara Costa, Dalila Bevilacqua, Federica Calzetti, Nicola Tamassia, Cecilia Spina, Donata De Sabata, Elisa Tinazzi, Claudio Lunardi, Maria T Scupoli, Chiara Cavallini, Elisa Zoratti, Ilaria Tinazzi, Antonio Marchetta, Aurora Vassanelli, Maurizio Cantini, Giorgio Gandini, Andrea Ruzzenente, Alfredo Guglielmi, Francesco Missale, William Vermi, Cristina Tecchio, Marco A Cassatella, Patrizia Scapini
The identification of discrete neutrophil populations, as well as the characterization of their immunoregulatory properties, is an emerging topic under extensive investigation. In such regard, the presence of circulating CD66b(+)-neutrophil populations, exerting either immunosuppressive or proinflammatory functions, has been described in several acute and chronic inflammatory conditions. However, due to the lack of specific markers, the precise phenotype and maturation status of these neutrophil populations remain unclear...
January 4, 2017: Blood
https://www.readbyqxmd.com/read/28050230/givinostat-a-type-ii-histone-deacetylase-inhibitor-induces-potent-caspase-dependent-apoptosis-in-human-lymphoblastic-leukemia
#3
Ying Li, Kevin Zhao, Chenjiao Yao, Samir Kahwash, Yan Tang, Guojiuan Zhang, Kara Patterson, Qi-En Wang, Weiqiang Zhao
Unlike chronic myeloid leukemia, patients with acute lymphoblastic leukemia (ALL) with Philadelphia chromosome (Ph+) do not respond well to Imatinib or tyrosine kinase inhibitors (TKI). In addition, TKI might induce resistant mutations in kinase domain (KD) of ABL in patients with relapsed diseases. Of the histone deacetylase (HDAC) inhibitors, suberoylanilide hydroxamic acid (SAHA) has shown to induce potent cytotoxicity on acute myeloid leukemia cell lines but Givinostat effect on acute lymphoblastic leukemia (ALL) has not been reported...
September 2016: Genes & Cancer
https://www.readbyqxmd.com/read/28032244/dasatinib-a-review-in-chronic-myeloid-leukaemia-and-ph-acute-lymphoblastic-leukaemia
#4
Gillian M Keating
Dasatinib (Sprycel(®)) is an orally administered, small molecule inhibitor of multiple tyrosine kinases. In the phase 3 DASISION trial, dasatinib 100 mg once daily resulted in deeper and faster cytogenetic and molecular responses than imatinib 400 mg once daily in patients with newly diagnosed, chronic-phase chronic myeloid leukaemia (CML), although there was no significant between-group difference in progression-free survival (PFS) or overall survival (OS) in the longer term. In the phase 3 CA180-034 trial, a regimen of dasatinib 100 mg once daily provided the most favourable benefit-risk profile in patients with imatinib-resistant or -intolerant chronic-phase CML...
January 2017: Drugs
https://www.readbyqxmd.com/read/28024490/-allogeneic-hematopoietic-stem-cell-transplantation-for-treatment-of-t-cell-lymphoblastic-lymphoma-clinical-observation-of-10-cases
#5
Fang Gong, Heng Chen, Lin-Yan Zhao, Tong Wang, Ri Zhang, De-Pei Wu
OBJECTIVE: To analyze the result of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for treatment of patients with T cell Lymphoblastic lymphoma(T-LBL). METHODS: The engraftment, graft versus host disease (GVHD), infection, relapse and survival of 10 T-LBL patients received allo-HSCT was observed. The clinical outcome of allo-HSCT for T-LBL patients was analyzed. RESULTS: The median age of patients was 25 years old, 10 (6 males and 4 females) T-LBL patients received allo-HSCT including 3 from HLA-matched unrelated donors, 3 from HLA-matched sibling donors, 2 from HLA haploidentical sibling donors, and 2 from haploidentical related donors...
December 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28013106/cpx-351-exhibits-potent-and-direct-ex-vivo-cytotoxicity-against-aml-blasts-with-enhanced-efficacy-for-cells-harboring-the-flt3-itd-mutation
#6
Max J Gordon, Paul Tardi, Marc M Loriaux, Stephen E Spurgeon, Elie Traer, Tibor Kovacsovics, Lawrence D Mayer, Jeffrey W Tyner
PURPOSE: Identify AML patients most likely to respond to CPX-351, a nano-scale liposome formulation containing cytarabine and daunorubicin co-encapsulated at a 5:1 molar ratio. METHODS: We examined the ex vivo cytotoxic activity of CPX-351 against leukemic cells isolated from 53 AML patients and an additional 127 samples including acute lymphoblastic leukemia, myelodysplastic syndrome/myeloproliferative neoplasms, or chronic lymphocytic leukemia/lymphoma. We assessed activity with respect to common molecular lesions and used flow cytometry to assess CPX-351 cellular uptake...
December 12, 2016: Leukemia Research
https://www.readbyqxmd.com/read/27983886/graft-versus-host-disease-in-adolescents-and-young-adults-15-24-years-old-after-allogeneic-hematopoietic-stem-cell-transplantation-for-acute-leukemia-in-first-complete-remission
#7
Marguerite Vignon, Annalisa Andreoli, Nathalie Dhédin, Etienne Lengliné, Emeline Masson, Marie Robin, Clémence Granier, Jérôme Larghero, Marie-Hélène Schlageter, Régis Peffault de Latour, Gérard Socié, Nicolas Boissel
PURPOSE: Adolescents and young adults (AYAs) with cancer are a unique group of patients in terms of disease incidence and biology, outcome, and psychosocial needs. This study aims to correlate the risk of graft-versus-host disease (GvHD) and age in a population of children and young adults with acute leukemia undergoing hematopoietic stem cell transplantation (HSCT) in first complete remission (CR). METHODS: We analyzed the outcome of 153 consecutive children (<15 years), AYAs (15-24 years), and adults (25-35 years) with lymphoblastic or myeloid acute leukemia in first CR who underwent HSCT with matched donors after myeloablative conditioning...
December 16, 2016: Journal of Adolescent and Young Adult Oncology
https://www.readbyqxmd.com/read/27981789/comparison-of-abnormal-cell-flagging-of-the-hematology-analyzers-sysmex-xn-and-sysmex-xe-5000-in-oncohematologic-patients
#8
J R Furundarena, M Sainz, A Uranga, L Cuevas, I Lopez, J Zubicaray, A Bizjak, N Robado, M Araiz
INTRODUCTION: Hematology analyzers should optimize flagging while minimizing false-negative results and unnecessary microscopic reviews. METHODS: We compared flagging performance of Sysmex XE-5000 and XN analyzers in oncohematologic patients. Differential counts were performed by Cellavision digital system (100 cells) and a hematologist (another 100 cells). RESULTS: First, we included 292 samples (86 with blasts): 28 acute lymphoblastic leukemia, 88 acute myeloid leukemia, 91 myelodysplastic syndromes, 45 chronic myeloproliferative neoplasms, and 40 chronic myelomonocytic leukemia...
December 16, 2016: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/27977050/the-promise-of-chimeric-antigen-receptor-t-cells-carts-in-leukaemia
#9
REVIEW
Robert J Orlowski, David L Porter, Noelle V Frey
The success of genetically engineered T cells that express chimeric antigen receptors (CARTs) has been a momentous step forward in harnessing the potent cancer fighting abilities of the immune system. The efficacy seen in relapsed/refractory (r/r) acute lymphoblastic leukaemia (ALL), not only by inducing remission, but also in maintaining long-term disease control, has been unprecedented. While the foundation for this approach has been firmly set in place, continued development will improve the efficacy, toxicity and applicability to other malignancies of this new class of 'living drugs'...
December 15, 2016: British Journal of Haematology
https://www.readbyqxmd.com/read/27934561/various-regimens-of-total-body-irradiation-for-hematopoietic-stem-cell-transplant
#10
Naoya Ishibashi, Toshiya Maebayashi, Takuya Aizawa, Masakuni Sakaguchi, Osamu Abe, Kazuyoshi Sakanishi, Yuji Endoh, Tsutomu Saito, Jiro Kawamori, Yoshiaki Tanaka
OBJECTIVES: We aimed to evaluate the safety of total body irradiation before bone marrow transplant. MATERIALS AND METHODS: We analyzed 110 patients (65 male, 45 female) who underwent total body irradiation for hematopoietic stem cell transplant between May 1998 and March 2013. Median age at total body irradiation was 17 years (range, 1-62 y). Median observation time was 777 days (range, 31-5494 d). Initial diagnoses were acute lymphoblastic leukemia (24 patients), acute myeloid leukemia (26 patients), chronic myeloid leukemia (7 patients), myelodysplastic syndrome (8 patients), malignant lymphoma (13 patients), mucopolysaccharidosis (12 patients), neuroblastoma (10 patients), and other diseases (10 patients)...
December 2016: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/27932188/successful-single-lung-transplant-for-severe-lung-graft-versus-host-disease-two-years-after-sibling-allograft-for-acute-lymphoblastic-leukemia-a-case-report
#11
M R Irhimeh, M Musk, J P Cooney
Bone marrow transplantation (BMT) has been performed as a successful life-saving treatment for hematological and neoplastic diseases. Despite the predictable long-term survival rates in BMT, pulmonary complications reduce the survival rates significantly mainly because of chronic graft-versus-host disease (GVHD). This report briefly discusses a successful lung transplantation case for severe lung GVHD after allograft for acute lymphoblastic leukemia. This case report supports the scarce evidence in the literature for the importance of lung transplantation as a therapeutic option for patients who develop respiratory failure secondary to BMT...
November 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27906795/factors-determining-the-outcome-of-hematopoietic-stem-cell-transplantation-in-patients-with-acute-lymphoblastic-leukemia-at-king-faisal-specialist-hospital-and-research-center-riyadh-saudi-arabia
#12
Suleimman Al-Sweedan, Amal Al-Seraihy, Ali Al-Ahmari, Abdullah Al-Jefri, Viqaruddin Mohammed, Rafat Jafri, Khawar Siddiqui, Mouhab Ayas
Medical records of 82 patients with acute lymphoblastic leukemia (ALL) who underwent hematopoietic cell transplantation (HCT) at our institution from 2005 to 2011 were reviewed. Forty-five patients were male (54.8%). The median age at HCT was 7.46 years (range, 0.98 to 14.31 y), the median time to HCT after diagnosis was 12.56 months. Ten patients were below the age of 1 year (12%). All patients were in complete remission at the time of HCT. In 83 transplants, 64 patients received HCT from human leukocyte antigen-identical-related donors and 19 from other donors...
January 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/27903673/combining-anti-mir-155-with-chemotherapy-for-the-treatment-of-lung-cancers
#13
Katrien Van Roosbroeck, Francesca Fanini, Tetsuro Setoyama, Cristina Ivan, Cristian Rodriguez-Aguayo, Enrique Fuentes-Mattei, Lianchun Xiao, Ivan Vannini, Roxana Redis, Lucilla D'Abundo, Xinna Zhang, Milena S Nicoloso, Simona Rossi, Vianey Gonzalez-Villasana, Rajesha Rupaimoole, Manuela Ferracin, Fortunato Morabito, Antonino Neri, Peter Ruvolo, Vivian R Ruvolo, Chad V Pecot, Dino Amadori, Lynne Aruzzo, Steliana Calin, Xuemei Wang, M James You, Alessandra Ferrajoli, Robert Z Orlowski, William Plunkett, Tara Lichtenberg, Ramana V Davuluri, Ioana Berindan-Neagoe, Massimo Negrini, Ignacio I Wistuba, Kantarjian Hagop, Anil K Sood, Gabriel Lopez-Berestein, Michael J Keating, Muller Fabbri, George A Calin
Purpose The oncogenic miR-155 is upregulated in many human cancers and its expression is increased in more aggressive and therapy resistant tumors, but the molecular mechanisms underlying miR-155-induced therapy resistance are not fully understood. The main objectives of this study were to determine the role of miR-155 in resistance to chemotherapy and to evaluate anti-miR-155 treatment to chemosensitize tumors. Experimental Design We performed in vitro studies on cell lines to investigate the role of miR-155 in therapy resistance...
November 30, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27899971/the-targetable-role-of-herpes-virus-associated-ubiquitin-specific-protease-hausp-in-p190-bcr-abl-leukemia
#14
Giovanna Carrà, Cristina Panuzzo, Sabrina Crivellaro, Deborah Morena, Riccardo Taulli, Angelo Guerrasio, Giuseppe Saglio, Alessandro Morotti
Philadelphia chromosome-positive (Ph(+)) acute lymphoblastic leukemia (ALL) is driven by the p190 breakpoint cluster region (BCR)-ABL isoform. Although effectively targeted by BCR-ABL tyrosine kinase inhibitors (TKIs), ALL is associated with a less effective response to TKIs compared with chronic myeloid leukemia. Therefore, the identification of additional genes required for ALL maintenance may provide possible therapeutic targets to aid the eradication of this cancer. The present study demonstrated that p190 BCR-ABL is able to interact with the deubiquitinase herpesvirus-associated ubiquitin-specific protease (HAUSP), which in turn affects p53 protein stability...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27899822/mir-150-exerts-antileukemia-activity-in-vitro-and-in-vivo-through-regulating-genes-in-multiple-pathways
#15
Zhi Hong Fang, Si Li Wang, Jin Tao Zhao, Zhi Juan Lin, Lin Yan Chen, Rui Su, Si Ting Xie, Bing Z Carter, Bing Xu
MicroRNAs, a class of small noncoding RNAs, have been implicated to regulate gene expression in virtually all important biological processes. Although accumulating evidence demonstrates that miR-150, an important regulator in hematopoiesis, is deregulated in various types of hematopoietic malignancies, the precise mechanisms of miR-150 action are largely unknown. In this study, we found that miR-150 is downregulated in samples from patients with acute lymphoblastic leukemia, acute myeloid leukemia, and chronic myeloid leukemia, and normalized after patients achieved complete remission...
September 22, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27881582/the-expanding-role-of-the-bcl6-oncoprotein-as-a-cancer-therapeutic-target
#16
Mariano G Cardenas, Erin Oswald, Wenbo Yu, Fengtian Xue, Alexander D MacKerell, Ari M Melnick
BCL6 was initially discovered as an oncogene in B-cell lymphomas, where it drives the malignant phenotype by repressing proliferation and DNA damage checkpoints and blocking B-cell terminal differentiation. BCL6 mediates its effects by binding to hundreds of target genes, and then repressing these genes by recruiting several different chromatin modifying corepressor complexes. Structural characterization of BCL6-corepressor complexes suggested that BCL6 might be a druggable target. Accordingly a number of compounds have been designed to bind to BCL6 and block corepressor recruitment...
November 23, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27880933/immunological-effects-of-nilotinib-prophylaxis-after-allogeneic-stem-cell-transplantation-in-patients-with-advanced-chronic-myeloid-leukemia-or-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia
#17
Nira Varda-Bloom, Ivetta Danylesko, Roni Shouval, Shiran Eldror, Atar Lev, Jacqueline Davidson, Esther Rosenthal, Yulia Volchek, Noga Shem-Tov, Ronit Yerushalmi, Avichai Shimoni, Raz Somech, Arnon Nagler
Allogeneic stem cell transplantation remains the standard treatment for resistant advanced chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia. Relapse is the major cause of treatment failure in both diseases. Post-allo-SCT administration of TKIs could potentially reduce relapse rates, but concerns regarding their effect on immune reconstitution have been raised. We aimed to assess immune functions of 12 advanced CML and Ph+ ALL patients who received post-allo-SCT nilotinib...
November 18, 2016: Oncotarget
https://www.readbyqxmd.com/read/27875673/recent-advances-in-engineered-t-cell-therapies-targeting-b-cell-malignancies
#18
Nathan Singh
Immunotherapy using engineered autologous T cells has been attempted for decades, but clinical trials have only recently demonstrated efficacy. The combination of enhanced manufacturing techniques, highly efficient engineering, appropriate target selection and synthetic receptors with potent T cell activating domains has led to the development of highly-active cellular therapy products. B-cell malignancies have served as the paradigmatic diseases to initially evaluate and subsequently hone engineered T cells targeting cancer...
October 2016: Discovery Medicine
https://www.readbyqxmd.com/read/27870504/chronic-licl-pretreatment-suppresses-thrombin-stimulated-intracellular-calcium-mobilization-through-trpc3-in-astroglioma-cells
#19
Takuji Uemura, Marty Green, Jerry J Warsh
OBJECTIVES: Transient receptor potential canonical type 3 (TRPC3) channels are activated in B lymphoblast cell lines from patients with bipolar disorder (BD), and its expression is reduced by chronic lithium treatment, implicating TRPC3 in the intracellular calcium (Ca(2+) ) dyshomeostasis of BD. Thrombin, via a protease-activated receptor, moderates Ca(2+) signaling and TRPC3 in astrocytes, and also cell proliferation. We examined whether lithium pretreatment attenuates thrombin-stimulated TRPC3 expression and function in astrocytes, and levels of the calcium-binding peptide, S100B, which is expressed mainly in these cells...
November 2016: Bipolar Disorders
https://www.readbyqxmd.com/read/27865176/adoptive-immunotherapy-for-hematological-malignancies-current-status-and-new-insights-in-chimeric-antigen-receptor-t-cells
#20
REVIEW
Alessandro Allegra, Vanessa Innao, Demetrio Gerace, Doriana Vaddinelli, Caterina Musolino
Hematological malignancies frequently express cancer-associated antigens that are shared with normal cells. Such tumor cells elude the host immune system because several T cells targeted against self-antigens are removed during thymic development, and those that persist are eliminated by a regulatory population of T cells. Chimeric antigen receptor-modified T cells (CAR-Ts) have emerged as a novel modality for tumor immunotherapy due to their powerful efficacy against tumor cells. These cells are created by transducing genes-coding fusion proteins of tumor antigen-recognition single-chain Fv connected to the intracellular signaling domains of T cell receptors, and are classed as first-, second- and third-generation, differing on the intracellular signaling domain number of T cell receptors...
November 2016: Blood Cells, Molecules & Diseases
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