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Qiuyun Fang, Tian Yuan, Yan Li, Juan Feng, Xiaoyuan Gong, Qinghua Li, Xingli Zhao, Kaiqi Liu, Kejing Tang, Zheng Tian, Qi Zhang, Ying Wang, Bingcheng Liu, Min Wang, Kun Ru, Jianxiang Wang, Yingchang Mi
The multiplex ligation-dependent probe amplification (MLPA) method was used to detect the copy number alterations (CNAs) of IKAROS family zinc finger 1 ( IKZF1 ), paired box 5 ( PAX5 ), ETS variant 6 ( ETV6 ), RB transcriptional corepressor 1 ( RB1 ), BTG anti-proliferation factor 1 ( BTG1 ), early B-cell factor 1 ( EBF1 ), cyclin dependent kinase inhibitor 2A/2B ( CDKN2A/2B ) and cytokine receptor like factor 2 ( CRLF2 ) genes in 87 adults with acute lymphoblastic leukemia (ALL) in China. The effects of CNAs on prognosis were analyzed...
April 2018: Oncology Letters
Fatemeh Izadpanah Qeshmi, Ahmad Homaei, Pedro Fernandes, Sedigheh Javadpour
The marine environment is a rich source of biological and chemical diversity. It covers more than 70% of the Earth's surface and features a wide diversity of habitats, often displaying extreme conditions, where marine organisms thrive, offering a vast pool for microorganisms and enzymes. Given the dissimilarity between marine and terrestrial habitats, enzymes and microorganisms, either novel or with different and appealing features as compared to terrestrial counterparts, may be identified and isolated. L-asparaginase (E...
March 2018: Microbiological Research
F Yang, J Zhang, H Y Qiu, Q Wu, D Q Kong, J J Han, J Q Qi, Y Han, D P Wu
No abstract text is available yet for this article.
January 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
Maria Maruffi, Richard Sposto, Matthew J Oberley, Lynn Kysh, Etan Orgel
The rarity of mixed-phenotype acute leukemia (MPAL) has resulted in diffuse literature consisting of small case series, thus precluding a consensus treatment approach. We conducted a meta-analysis and systematic review to investigate the association of treatment type (acute lymphoblastic leukemia [ALL], acute myeloid leukemia [AML], or "hybrid" regimens), disease response, and survival. We searched seven databases from inception through June 2017 without age or language restriction. Included studies reported sufficient treatment detail for de novo MPAL classified according to the well-established European Group for Immunological Characterization of Acute Leukemias (EGIL) or World Health Organization (WHO2008) criteria...
February 27, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Asaf D Yanir, Caridad A Martinez, Ghadir Sasa, Kathryn Leung, Stephen Gottschalk, Bilal Omer, Nabil Ahmed, Meenakshi Hegde, Jo Eunji, Hao Liu, Helen E Heslop, Malcolm K Brenner, Robert A Krance, Swati Naik
Hematopoietic stem cell transplantation (HSCT) is the only curative option for a subset of patients with high-risk or relapsed Acute Lymphoblastic Leukemia (ALL). Given evolving practices, it is important to continually evaluate outcomes for pediatric ALL following HSCT. Outcomes after HSCT are influenced by the type of donor used as this determines the degree and method of T-cell depletion used, and consequently, specific transplant-related morbidities. We retrospectively analyzed HSCT data from our center for transplants performed between January 2008 and May 2016, comparing outcomes between different donor types...
March 14, 2018: Biology of Blood and Marrow Transplantation
Maro Ohanian, Ana Tari Ashizawa, Guillermo Garcia-Manero, Naveen Pemmaraju, Tapan Kadia, Elias Jabbour, Farhad Ravandi, Gautam Borthakur, Michael Andreeff, Marina Konopleva, Miranda Lim, Sherry Pierce, Susan O'Brien, Yesid Alvarado, Srdan Verstovsek, William Wierda, Hagop Kantarjian, Jorge Cortes
BACKGROUND: Activating mutations of tyrosine kinases are common in leukaemias. Oncogenic tyrosine kinases use the growth factor receptor-bound protein 2 (Grb2) for signal transduction, leading to activation of mitogen-activated protein kinase (MAPK) 1 and MAPK3 (ERK2 and ERK1). We hypothesised that inhibition of Grb2 would suppress ERK1 and ERK2 activation and inhibit leukaemia progression. To inhibit Grb2, a liposome-incorporated antisense oligodeoxynucleotide that blocks Grb2 protein expression, BP1001, was developed...
March 14, 2018: Lancet Haematology
Priscila Pini Zenatti, Natacha Azussa Migita, Nathália Moreno Cury, Rosângela Aparecida Mendes-Silva, Fabio Cesar Gozzo, Pedro Otavio de Campos-Lima, José Andrés Yunes, Silvia Regina Brandalise
The drug l-asparaginase is a cornerstone in the treatment of acute lymphoblastic leukemia (ALL). The native E. colil-asparaginase used in Brazil until recently has been manufactured by Medac/Kyowa. Then a decision was taken by the Ministry of Health in 2017 to supply the National Health System with a cheaper alternative l-asparaginase manufactured by Beijing SL Pharmaceutical, called Leuginase®. As opposed to Medac, the asparaginase that has been in use in Brazil under the trade name of Aginasa®, it was not possible to find a single entry with the terms Leuginase in the Pubmed repository...
March 9, 2018: EBioMedicine
Fabiën N Belle, Juliane Wenke-Zobler, Eva Cignacco, Ben D Spycher, Roland A Ammann, Claudia E Kuehni, Karin Zimmermann
BACKGROUND: Childhood cancer patients (CCP) have been reported to be at increased risk of becoming overweight during treatment. We assessed prevalence of overweight in CCP at diagnosis and at the end of treatment, determined risk factors, and identified weight change during treatment by type of cancer. METHODS: In a multicentre cohort study, we collected height and weight measurements of CCP at diagnosis and repeatedly during treatment. We calculated age- and sex-adjusted BMI Z-scores using references of the International Obesity Taskforce for children...
March 2, 2018: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
Reibán-Espinoza Esteban, Bourlon Christianne, Aguayo Alvaro, Demichelis-Gómez Roberta
INTRODUCTION: The expression of the CD20 on adult B-cell acute lymphoblastic leukemia (ALL-B) has generally been associated with a poor prognosis, and several studies have explored the incorporation of rituximab into the therapeutic regimen for adult ALL-B patients, with a positive effect on event-free survival (EFS). PATIENTS AND METHODS: We analyzed the prognostic value of CD20 expression and the effect of rituximab for the treatment of Hispanic adult ALL-B patients...
February 26, 2018: Clinical Lymphoma, Myeloma & Leukemia
Hamid Reza Mirzaei, Hossein Pourghadamyari, Majid Rahmati, Abbas Mohammadi, Javid Sadri Nahand, Abbas Rezaei, Hamed Mirzaei, Jamshid Hadjati
Recently clinical trials utilizing genetically engineered T cells expressing a chimeric antigen receptor (CAR) that is half monoclonal antibody and half T-cell receptor have demonstrated remarkable response in patients with advanced cancers like relapsed or refractory acute lymphoblastic leukemia (ALL) and lymphoma. Moreover, emerging chimeric genome editing tools such as zinc-finger nucleases (ZNFs), transcription activator-like effector nucleases (TALENs) and clustered regulatory interspaced short palindromic repeat (CRISPR)/Cas composed of sequence-specific DNA binding module(s) linked to a non-specific DNA cleavage domain have made possible to dramatically expand the ability to manipulate cells aim to treat and/or study a wide range of diseases including cancer...
March 12, 2018: Cancer Letters
Li-Na Zhang, Yongping Song, Delong Liu
The prognosis of adults with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) remains dismal even at this day and age. With salvage chemotherapy, only 29% (range 18 to 44%) of the patients with R/R ALL can be induced into complete remission (CR), with a median overall survival (OS) of 4 months (range 2-6 months). Blinatumomab and inotuzumab ozogamycin (IO) are immunotherapeutic agents that increased CR to 80% and extended survival to 7.7 months in this high-risk population of patients. In the last few years, chimeric antigen receptor (CAR)--engineered T cells have led to major progress in cancer immunotherapy...
March 15, 2018: Journal of Hematology & Oncology
Qingkai Dai, Xiaojuan Liu, Hui Yang, Siqi Guo, Yuefang Wang, Luyun Peng, Lei Ye, Lan Chen, Chunqi Lai, Qi Chen, Ge Zhang, Yongmei Jiang
Detection of aberrant antigen expression in acute lymphoblastic leukemia (ALL) by flow cytometric is proposed for the quantification of minimal residual disease (MRD). There are few studies that investigate the stability of the antigen expression in children with B lineage ALL at the end of remission induction therapy and determine its prognostic impact. Between 2010 and 2015, 691 bone marrow specimens of childhood ALL were sent at diagnosis for immunophenotypic characterization, and follow-up samples for MRD were analyzed on day 33...
March 2, 2018: Leukemia Research
Natthakan Thongon, Chiara Zucal, Vito Giuseppe D'Agostino, Toma Tebaldi, Silvia Ravera, Federica Zamporlini, Francesco Piacente, Ruxanda Moschoi, Nadia Raffaelli, Alessandro Quattrone, Alessio Nencioni, Jean-Francois Peyron, Alessandro Provenzani
Background: Inhibitors of nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in NAD+ biosynthesis from nicotinamide, exhibit anticancer effects in preclinical models. However, continuous exposure to NAMPT inhibitors, such as FK866, can induce acquired resistance. Methods: We developed FK866-resistant CCRF-CEM (T cell acute lymphoblastic leukemia) and MDA MB231 (breast cancer) models, and by exploiting an integrated approach based on genetic, biochemical, and genome wide analyses, we annotated the drug resistance mechanisms...
2018: Cancer & Metabolism
Yimei Ma, Xizhou An, Xianmin Guan, Qinglin Kong, Yanzhen Wang, Pengfei Li, Yan Meng, Yinghui Cui, Xianhao Wen, Yuxia Guo, Yali Shen, Jie Yu
Phosphoribosyl pyrophosphate synthetase 1 (PRPS1) is closely associated with a number of diseases; however, its influence in B-cell acute lymphoblastic leukemia (B-ALL) and the potential molecular mechanisms involved remain unclear. The present study aimed to evaluate the expression of PRPS1 in Chinese children with B-ALL and to investigate the mechanism of action of PRPS1 in this disease. A Cell Counting Kit-8 (CCK-8) assay was performed to examine the proliferation of B-ALL Sup-B15 and Raji cells, and flow cytometric analysis was conducted to determine the cell cycle distribution and rate of apoptosis...
April 2018: Oncology Letters
Amara Gul, Sadia Zafar
The objective of the current study was to compare cognitive flexibility and emotion regulation between childhood survivors of Acute Lymphoblastic Leukaemia (ALL) and healthy control subjects. Twenty-five childhood survivors of ALL treated with intrathecal chemotherapy between 2013 to 2016 from Shaukat Khanum Memorial Cancer Hospital, Children Hospital and Jinnah Hospital Lahore and twenty-five healthy demographically matched children (control group) participated in the study. Participants performed task switching experiment as a measure of cognitive flexibility and emotion regulation questionnaire for children and adolescents...
March 2018: JPMA. the Journal of the Pakistan Medical Association
Lisa M Ebert, Wenbo Yu, Tessa Gargett, Michael P Brown
Chimeric antigen receptor (CAR)-T cell therapy has been clinically validated as a curative treatment for the difficult to treat malignancies of relapsed/refractory B-cell acute lymphoblastic leukaemia and lymphoma. Here, the CAR-T cells are re-directed towards a single antigen, CD19, which is recognised as a virtually ideal CAR target antigen because it has strong, uniform expression on cancer cells, and is otherwise expressed only on healthy B cells, which are 'dispensable'. Notwithstanding the clinical success of CD19-CAR-T cell therapy, its single specificity has driven therapeutic resistance in 30% or more of cases with CD19-negative leukaemic relapses...
March 14, 2018: Biochemical Society Transactions
Heng Xu, Yang Shu
Treatment outcomes for acute lymphoblastic leukemia (ALL), especially pediatric ALL, have greatly improved due to the risk-adapted therapy. Combination of drug development, clinical practice, as well as basic genetic researches has brought the survival rate of ALL from less than 10% to more than 90% today, not only increasing the treatment efficacy but also limiting adverse drug reactions (ADRs). In this review, we summarized the landscape identification of ALL genetic alterations, which provided the opportunity to increase the survival rate and especially minimize the relapse risk of ALL, and highlighted the importance of the development of new technologies of genomic investigation for translational medicine...
2018: Methods in Molecular Biology
Aleš Hnízda, Milan Fábry, Takaya Moriyama, Petr Pachl, Michael Kugler, Vítězslav Brinsa, David B Ascher, William L Carroll, Petr Novák, Markéta Žaliová, Jan Trka, Pavlína Řezáčová, Jun J Yang, Václav Veverka
Activating mutations in NT5C2, a gene encoding cytosolic purine 5'-nucleotidase (cN-II), confer chemoresistance in relapsed acute lymphoblastic leukemia. Here we show that all mutants became independent of allosteric effects of ATP and thus constitutively active. Structural mapping of mutations described in patients demonstrates that 90% of leukemia-specific allelles directly affect two regulatory hotspots within the cN-II molecule-the helix A region: residues 355-365, and the intersubunit interface: helix B (232-242) and flexible interhelical loop L (400-418)...
February 25, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Sarah D Cramer, Julie A Hixon, Caroline Andrews, Ross J Porter, Gisele O L Rodrigues, Xiaolin Wu, Tim Back, Kelli Czarra, Helen Michael, Maggie Cam, Jack Chen, Dominic Esposito, Emilee Senkevitch, Vijay Negi, Peter D Aplan, Wenqing Li, Scott K Durum
No abstract text is available yet for this article.
February 15, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Paweł Borowiecki, Patrycja Wińska, Maria Bretner, Małgorzata Gizińska, Mirosława Koronkiewicz, Monika Staniszewska
Three out of 16 newly synthesized 1,3-dimethylxanthine derivatives (proxyphylline analogues) exhibited consistencies between antifungal and anticancer properties. Proxyphylline possessing 1-(10H-phenothiazin-10-yl)propan-2-yl (6) and polybrominated benzimidazole (41) or benzotriazole moiety (42) remained selectively cidal against Candida albicans (lg R ≥ 3 at conc. of 31, 36 and 20 μM, respectively) however not against normal mammalian Vero cell line in vitro (IC50  ≥ 280 μM) and Galleria mellonella in vivo...
February 27, 2018: European Journal of Medicinal Chemistry
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