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Leukemia biomarker

Ami N Shah, William J Gradishar
Anthracyclines have been a mainstay of breast cancer therapy for decades, with strong evidence demonstrating their impact on breast cancer survival. However, concerns regarding rare but serious long-term toxicities including cardiotoxicity and hematologic malignancies have driven interest in alternative adjuvant therapy options with more favorable toxicity profiles. This article provides an update of data that help inform clinicians of the role anthracyclines should play in adjuvant breast cancer therapy. Two recently reported large randomized trials-the Anthracycline in Early Breast Cancer and Western German Study Plan B studies-compared a taxane and cyclophosphamide regimen with an anthracycline, taxane, and cyclophosphamide regimen...
August 17, 2018: Oncologist
Yun Jung Choi, Hi-Jung Park, Hye Jin Park, Kyeong Cheon Jung, Jae-Il Lee
Peripheral CD4/CD8 double-positive (DP) T cells are associated with autoimmune disorders, cancer, and viral infection. However, the relationship between organ transplantation and DP T cells is unclear. Here, we examined the functional characteristics of peripheral DP T cells and analyzed their significance with respect to islet graft rejection in a nonhuman primate model of islet transplantation. DP T cells were functionally equivalent to conventional CD4 and CD8 T cells in terms of helper and cytotoxic activity, respectively...
2018: Journal of Immunology Research
Harinad B Maganti, Hani Jrade, Christopher Cafariello, Janet L Manias Rothberg, Christopher J Porter, Julien Yockell-Lelièvre, Hannah L Battaion, Safwat T Khan, Joel P Howard, Yuefeng Li, Adrian T Grzybowski, Elham Sabri, Alexander J Ruthenburg, F Jeffrey Dilworth, Theodore J Perkins, Mitchell Sabloff, Caryn Y Ito, William L Stanford
Deep sequencing has revealed that epigenetic modifiers are the most mutated genes in acute myeloid leukemia (AML). Thus, elucidating epigenetic dysregulation in AML is crucial to understand disease mechanisms. Here, we demonstrate that Metal Response Element Binding Transcription Factor 2/Polycomblike 2 (MTF2/PCL2) plays a fundamental role in the Polycomb repressive complex 2 (PRC2) and that its loss elicits an altered epigenetic state underlying refractory AML. Unbiased systems analyses identified the loss of MTF2-PRC2 repression of MDM2 as central to, and therefore a biomarker for, refractory AML...
August 16, 2018: Cancer Discovery
Xiaoqian Jing, Haoxuan Wu, Xi Cheng, Xianze Chen, Yaqi Zhang, Minmin Shi, Tao Zhang, Xiongjun Wang, Ren Zhao
OBJECTIVES: Colorectal cancer (CRC), one of the most aggressive gastrointestinal malignancies, is a frequently diagnosed life-threatening cancer worldwide. Most CRC patients have poor prognosis mainly because of frequent metastasis and recurrence. Thus, it is crucial to find out some new biomarkers and to show deeper insights into the mechanisms of CRC. MLLT10, Myeloid/lymphoid or mixed-lineage leukemia translocated to 10, also known as AF10, a recurrent MLL partner. In this study, we found that MLLT10 promotes CRC tumor invasion and metastasis both in vitro and in vivo...
August 13, 2018: Scandinavian Journal of Gastroenterology
Carina Intke, Sini Korpelainen, Sari Hämäläinen, Matti Vänskä, Irma Koivula, Esa Jantunen, Kari Pulkki, Auni Juutilainen
OBJECTIVE: The study aim was to compare the performance of interleukin-1 receptor antagonist (IL-1Ra) to C-reactive protein (CRP) and procalcitonin (PCT) in early prediction of the clinical course of febrile neutropenia. METHODS: The study population consisted of 86 consecutive patients with febrile neutropenia who received intensive chemotherapy for haematological malignancy between November 2009 and November 2012 at the adult haematology ward of Kuopio University Hospital...
August 12, 2018: European Journal of Haematology
Gunilla Enblad, Hannah Karlsson, Gustav Gammelgard, Jessica Wenthe, Tanja Lovgren, Rose-Marie Amini, Kristina I Wikstrom, Magnus Essand, Barbara Savoldo, Helene Hallbook, Martin Höglund, Gianpietro Dotti, Malcolm K Brenner, Hans Hagberg, Angelica Loskog
PURPOSE: CAR T cell therapy has been effective for patients with CD19+ B cell malignancies. Most studies have investigated second generation CARs with either CD28 or 4-1BB co-stimulatory domains in the CAR receptor. Here we describe the first clinical phase I/IIa trial using third generation CAR T cells targeting CD19 to evaluate safety and efficacy. EXPERIMENTAL DESIGN: Fifteen patients with B cell lymphoma or leukemia were treated with CAR T cells. The lymphoma patients received chemotherapy during CAR manufacture and eleven of fifteen were given low dose cyclophosphamide and fludarabine conditioning prior to CAR infusion...
August 10, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Madhvi Rajpurkar, Todd A Alonzo, Yi-Cheng Wang, Robert B Gerbing, Alan S Gamis, James H Feusner, John Gregory, Matthew A Kutny
Acute promyelocytic leukemia (APL) is characterized by a heightened risk of coagulopathy with significant morbidity and mortality. Here we report our evaluation of presenting white blood cell (WBC) and the International Society on Thrombosis and Haemostasis (ISTH) disseminated intravascular coagulation (DIC) scoring system as markers for early death and nonlethal coagulopathy in pediatric APL. We evaluated 79 pediatric patients treated on a Children's Oncology Group phase III clinical trial. There were 4 early deaths and 13 nonlethal, clinically significant (grade III to IV) coagulopathy events during induction...
August 8, 2018: Journal of Pediatric Hematology/oncology
Mara Simopoulou, Konstantinos Sfakianoudis, Nikolaos Antoniou, Evangelos Maziotis, Anna Rapani, Panagiotis Bakas, George Anifandis, Theodoros Kalampokas, Stamatis Bolaris, Agni Pantou, Konstantinos Pantos, Michael Koutsilieris
Assisted reproductive technology has evolved tremendously since the emergence of in vitro fertilization (IVF). In the course of the recent decade, there have been significant efforts in order to minimize multiple gestations, while improving percentages of singleton pregnancies and offering individualized services in IVF, in line with the trend of personalized medicine. Patients as well as clinicians and the entire IVF team benefit majorly from 'knowing what to expect' from an IVF cycle. Hereby, the question that has emerged is to what extent prognosis could facilitate toward the achievement of the above goal...
August 8, 2018: Systems Biology in Reproductive Medicine
Mette Dahl, Iben Daugaard, Maria Schertz Andersen, Thomas Birkballe Hansen, Kirsten Grønbæk, Jørgen Kjems, Lasse Sommer Kristensen
Circular RNAs (circRNAs) are covalently closed endogenous molecules with tissue- and disease-specific expression patterns, which have potential as diagnostic and prognostic biomarkers in cancer. The molecules are formed by a backsplicing event linking the 3'-end of an exon to the 5'-end of the same or an upstream exon, and they exert diverse regulatory functions important in carcinogenesis. The landscape of circRNA expression has not been characterized in B-cell malignancies, and current methods for circRNA quantification have several limitations that prevent development of clinically applicable assays...
August 7, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
Jialin Meng, Wanzhen Li, Meng Zhang, Zongyao Hao, Song Fan, Li Zhang, Chaozhao Liang
OBJECTIVE: Transporter associated with antigen processing protein (TAP) is a heterodimer protein consist of TAP1 and TAP2, act a pivotal part in the immune surveillance. In recent days, controversial relationships were reported between TAP polymorphisms and cancer risk, thus, a systematic meta-analysis was performed to resolve this discrepancy. METHODS: We searched the PubMed, EMbase, Web of Science, CNKI and Wanfang databases, the cited references were also manually searched again, covering all the papers published until March 25, 2018...
July 29, 2018: Pathology, Research and Practice
Huiqin Chen, Dihua Zhang, Guoping Zhang, Xiaofeng Li, Ying Liang, Mohan Vamsi Kasukurthi, Shengyu Li, Glen M Borchert, Jingshan Huang
BACKGROUND: Acute lymphoblastic leukemia is the most prevalent neoplasia among children. Despite the tremendous achievements of state-of-the-art treatment strategies, drug resistance is still a major cause of chemotherapy failure leading to relapse in pediatric acute lymphoblastic leukemia. The underlying mechanisms of such phenomenon are not yet clear and subject to further exploration. Prior research has shown that microRNAs can act as post-transcriptional regulators of many genes related to drug resistance...
July 23, 2018: BMC Medical Informatics and Decision Making
Yi-Xin Zou, Jia Qiao, Hua-Yuan Zhu, Rui-Nan Lu, Yi Xia, Lei Cao, Wei Wu, Hui Jin, Wen-Jie Liu, Jin-Hua Liang, Jia-Zhu Wu, Li Wang, Lei Fan, Wei Xu, Jian-Yong Li
Purpose: Chronic lymphocytic leukemia (CLL) is one of the most frequent type of B-cell chronic lymphoproliferative disorders and chronic inflammation takes part in the development of CLL. However, there has been no valid immune biomarker to predict the prognosis of untreated CLL patients. Materials and Methods: In this retrospective study, we analyzed the clinical correlations and prognostic value of albumin-to-fibrinogen ratio (AFR) detected at diagnosis in 191 CLL patients...
August 1, 2018: Cancer Research and Treatment: Official Journal of Korean Cancer Association
Miriam Marquis, Cyrielle Beaubois, Vincent-Philippe Lavallée, Michal Abrahamowicz, Coraline Danieli, Sébastien Lemieux, Imran Ahmad, Andrew Wei, Stephen B Ting, Shaun Fleming, Anthony Schwarer, David Grimwade, William Grey, Robert K Hills, Paresh Vyas, Nigel Russell, Guy Sauvageau, Josée Hébert
In acute myeloid leukemia (AML), risk stratification based on cytogenetics and mutation profiling is essential but remains insufficient to select the optimal therapy. Accurate biomarkers are needed to improve prognostic assessment. We analyzed RNA sequencing and survival data of 430 AML patients and identified HMGA2 as a novel prognostic marker. We validated a quantitative PCR test to study the association of HMGA2 expression with clinical outcomes in 358 AML samples. In this training cohort, HMGA2 was highly expressed in 22...
July 19, 2018: Blood Cancer Journal
Ann Vander Borght, Mieke Duysinx, Jos L V Broers, Monique Ummelen, Frank W Falkenberg, Christine Hahnel, Bernard A M van der Zeijst
Background: The Neural Cell Adhesion Molecule (NCAM) is a glycoprotein expressed as 120, 140 and/or 180 kDa isoforms, all derived through alternative splicing of a single gene. NCAM 120 contains no intracellular domain, whereas NCAM 140 and 180 have different intracellular domains determined by alternative splicing of exon 18. NCAM has been described as a biomarker to discriminate small cell lung cancer (SCLC) from non-SCLC (NSCLC). However, peripheral blood mononuclear cells (PBMC) also express NCAM...
June 2018: Translational Lung Cancer Research
Abdulraouf M Ramadan, Etienne Daguindau, Jason C Rech, Krishnapriya Chinnaswamy, Jilu Zhang, Greg L Hura, Brad Griesenauer, Zachary Bolten, Aaron Robida, Martha Larsen, Jeanne A Stuckey, Chao-Yie Yang, Sophie Paczesny
Soluble cytokine receptors function as decoy receptors to attenuate cytokine-mediated signaling and modulate downstream cellular responses. Dysregulated overproduction of soluble receptors can be pathological, such as soluble ST2 (sST2), a prognostic biomarker in cardiovascular diseases, ulcerative colitis, and graft-versus-host disease (GVHD). Although intervention using an ST2 antibody improves survival in murine GVHD models, sST2 is a challenging target for drug development because it binds to IL-33 via an extensive interaction interface...
July 25, 2018: JCI Insight
Ali Foroughi Pour, Lori Dalton
Optimal Bayesian Filtering (OBF) is a fast and memory-efficient algorithm that optimally identifies markers with distributional differences between treatment groups under Gaussian models. Here, we study the performance and robustness of OBF for biomarker discovery. Our contributions are twofold: (1) we examine how OBF performs on data that violates modeling assumptions, and (2) we provide guidelines on how to set input parameters for robust performance. Contribution (1) addresses an important, relevant and commonplace problem in computational biology, where it is often impossible to validate an algorithm's core assumptions...
July 23, 2018: IEEE/ACM Transactions on Computational Biology and Bioinformatics
Brandon L Pierce, Peter Kraft, Chenan Zhang
Purpose of review: In this paper, we summarize prior studies that have used Mendelian Randomization (MR) methods to study the effects of exposures, lifestyle factors, physical traits, and/or biomarkers on cancer risk in humans. Many such risk factors have been associated with cancer risk in observational studies, and the MR approach can be used to provide evidence as to whether these associations represent causal relationships. MR methods require a risk factor of interest to have known genetic determinants that can be used as proxies for the risk factor (i...
June 2018: Current Epidemiology Reports
Laura Cicconi, Pierre Fenaux, Hagop Kantarjian, Martin Tallman, Miguel A Sanz, Francesco Lo-Coco
Acute promyelocytic leukemia (APL) is a subtype of acute leukemia characterized by a unique t(15;17) translocation generating the PML/RARA fusion gene and hybrid oncoprotein. Besides its critical role in leukemogenesis, this genetic aberration serves as a disease-specific biomarker for rapid diagnosis and monitoring of minimal residual disease (MRD). Moreover, PML/RARA is specifically targeted by All-trans retinoic acid (ATRA) and arsenic trioxide (ATO), two agents that synergistically act to induce degradation of the oncoprotein...
July 19, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Tasia M Taxis, Marcus E Kehrli, Rui D'Orey-Branco, Eduardo Casas
Bovine leukemia virus (BLV) affects cattle health and productivity worldwide, causing abnormal immune function and immunosuppression. Transfer RNA fragments (tRFs) are known to be involved in inhibition of gene expression and have been associated with stress and immune response, tumor growth, and viral infection. The objective of this study was to identify tRFs associated with antibody response to BLV in Holstein cattle. Sera from 14 animals were collected to establish IgG reactivity to BLV by ELISA. Seven animals were seropositive (positive group) and seven were seronegative (negative group) for BLV exposure...
2018: Frontiers in Genetics
Vineeta Gupta, Sunil Kumar Singh, Vikas Agrawal, Tej Bali Singh
BACKGROUND: Several measures including drugs have been tried to reduce anthracycline cardiotoxicity. The lack of randomized trials prompted this study to assess the role of an angiotensin converting enzyme (ACE) inhibitor (enalapril) in anthracycline-induced cardiotoxicity in children with hematological malignancies. METHODS: A randomized, double-blind, placebo-controlled trial was conducted on 84 patients with leukemia (41) and lymphoma (43) who received anthracyclines (doxorubicin and/or daunorubicin) at cumulative dose ≥200 mg/m2 ...
July 15, 2018: Pediatric Blood & Cancer
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