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https://www.readbyqxmd.com/read/29775689/biomarkers-for-checkpoint-inhibition-in-hematologic-malignancies
#1
REVIEW
Djordje Atanackovic, Tim Luetkens
In the past few years we have seen remarkable paradigm shifts in the treatment of many solid tumors due to the introduction of inhibitors targeting immune checkpoints such as PD-1/PD-L1 and CTLA-4. Recent results indicate that checkpoint inhibition also represents a very promising approach for certain types of hematologic malignancies. Unfortunately, treatment with checkpoint inhibitors is also associated with substantial toxicities and high costs and only a subset of patients appears to derive clinical benefit from these treatments...
May 15, 2018: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29756258/a-prospective-analysis-of-circulating-saturated-and-monounsaturated-fatty-acids-and-risk-of-non-hodgkin-lymphoma
#2
Yu-Han Chiu, Kimberly A Bertrand, Shumin Zhang, Francine Laden, Mara M Epstein, Bernard A Rosner, Stephanie Chiuve, Hannia Campos, Edward L Giovannucci, Jorge E Chavarro, Brenda M Birmann
Circulating saturated (SFA) and monounsaturated fatty acids (MUFA), which are predominantly derived from endogenous metabolism, may influence non-Hodgkin lymphoma (NHL) risk by modulating inflammation or lymphocyte membrane stability. However, few biomarker studies have evaluated NHL risk associated with these fats. We conducted a prospective study of 583 incident NHL cases and 583 individually matched controls with archived pre-diagnosis red blood cell (RBC) specimens in the Nurses' Health Study (NHS) and Health Professionals Follow-up Study (HPFS)...
May 14, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29736400/the-international-prognostic-index-for-patients-with-chronic-lymphocytic-leukemia-has-the-higher-value-in-predicting-overall-outcome-compared-with-the-barcelona-brno-biomarkers-only-prognostic-model-and-the-md-anderson-cancer-center-prognostic-index
#3
Carolina Muñoz-Novas, María Poza-Santaella, Isabel González-Gascón Y Marín, María Hernández-Sánchez, Ana-Eugenia Rodríguez-Vicente, María-Stefania Infante, Cecilia Heras, María-Ángeles Foncillas, Karen Marín, Jesús-María Hernández-Rivas, José-Ángel Hernández
In recent years, new prognostic indexes (PIs) for chronic lymphocytic leukemia (CLL), which include clinical, biological, and genetic variables, have been validated, highlighting the MD Anderson Cancer Center prognostic index (MDACC PI), the CLL-international prognostic index (CLL-IPI), and the Barcelona-Brno biomarkers only prognostic model. The aim of this study is to compare the utility of these PIs in a cohort of Spanish patients. A retrospective analysis of 696 unselected CLL patients newly diagnosed and previously untreated from different Spanish institutions was performed...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29715621/elevated-mir-20b-5p-expression-in-peripheral-blood-mononuclear-cells-a-novel-independent-molecular-biomarker-of-favorable-prognosis-in-chronic-lymphocytic-leukemia
#4
Sotirios G Papageorgiou, Christos K Kontos, Panagiotis Tsiakanikas, Georgia Stavroulaki, Anthi Bouchla, Diamantina Vasilatou, Efthymia Bazani, Afroditi Lazarakou, Andreas Scorilas, Vasiliki Pappa
MicroRNA-20b-5p (miR-20b-5p) is part of the miR-106a/363 cluster and a member of the cancer-related miR-17 family. miR-20b-5p regulates important transcription factors, including hypoxia-inducible factor 1 (HIF1) and signal transducer and activator of transcription 3 (STAT3). Recently, the dysregulation of miR-20b-5p expression has been observed in many B-cell lymphomas and T-cell leukemias. In this research study, we examined the putative prognostic value of miR-20b-5p in CLL. Therefore, total RNA was isolated from peripheral blood mononuclear cells (PBMCs) collected from 88 CLL patients; next, total RNA was polyadenylated and first-strand cDNA was synthesized, using an oligo-dT-adapter primer...
April 26, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29713085/determinants-of-response-and-resistance-to-cd19-chimeric-antigen-receptor-car-t-cell-therapy-of-chronic-lymphocytic-leukemia
#5
Joseph A Fraietta, Simon F Lacey, Elena J Orlando, Iulian Pruteanu-Malinici, Mercy Gohil, Stefan Lundh, Alina C Boesteanu, Yan Wang, Roddy S O'Connor, Wei-Ting Hwang, Edward Pequignot, David E Ambrose, Changfeng Zhang, Nicholas Wilcox, Felipe Bedoya, Corin Dorfmeier, Fang Chen, Lifeng Tian, Harit Parakandi, Minnal Gupta, Regina M Young, F Brad Johnson, Irina Kulikovskaya, Li Liu, Jun Xu, Sadik H Kassim, Megan M Davis, Bruce L Levine, Noelle V Frey, Donald L Siegel, Alexander C Huang, E John Wherry, Hans Bitter, Jennifer L Brogdon, David L Porter, Carl H June, J Joseph Melenhorst
Tolerance to self-antigens prevents the elimination of cancer by the immune system1,2 . We used synthetic chimeric antigen receptors (CARs) to overcome immunological tolerance and mediate tumor rejection in patients with chronic lymphocytic leukemia (CLL). Remission was induced in a subset of subjects, but most did not respond. Comprehensive assessment of patient-derived CAR T cells to identify mechanisms of therapeutic success and failure has not been explored. We performed genomic, phenotypic and functional evaluations to identify determinants of response...
April 30, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29712993/development-of-a-quantitative-pcr-detecting-cunninghamella-bertholletiae-to-help-in-diagnosing-this-rare-and-aggressive-mucormycosis
#6
Anne-Pauline Bellanger, Ana Berceanu, Steffi Rocchi, Benoit Valot, Jean Fontan, Adrien Chauchet, Nicolas Belin, Emeline Scherer, Eric Deconinck, Jean-Christophe Navellou, Laurence Millon
Mucormycosis is an invasive mold infection, frequently fatal in immunocompromised patients. We report the case of a patient with chronic lymphocytic leukemia admitted to the hematology unit for febrile aplasia. Pulmonary lesions suggesting a fungal infection expanded/increased despite a combination of posaconazole and liposomal amphotericin B. The fungal biomarkers performed repeatedly were negative. At D65 after chemotherapy a bronchial biopsy was positive for Cunninghamella bertholletiae. The patient died despite appropriate antifungal management...
April 30, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29680229/zap-70-in-chronic-lymphocytic-leukemia-a-meta-analysis
#7
REVIEW
Yini Liu, Yangfeng Wang, Jule Yang, Yongyi Bi, Hong Wang
BACKGROUND: Recent studies have reported that zeta-chain-associated protein kinase 70 (ZAP-70) expression plays a prognostic role in chronic lymphocytic leukemia (CLL). However, these results remain controversial. Thus, we performed a meta-analysis to clarify the prognostic value of ZAP-70 expression in CLL. MATERIALS AND METHODS: Relevant studies were searched in PubMed, Embase, Cochrane library, and Web of Science up to January 2018. Clinicopathological features and prognostic data were extracted from the studies...
April 19, 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/29667176/pre-diagnostic-blood-immune-markers-incidence-and-progression-of-b-cell-lymphoma-and-multiple-myeloma-univariate-and-functionally-informed-multivariate-analyses
#8
Roel Vermeulen, Fatemeh Saberi Hosnijeh, Barbara Bodinier, Lützen Portengen, Benoît Liquet, Javiera Garrido-Manriquez, Henk Lokhorst, Ingvar A Bergdahl, Soterios A Kyrtopoulos, Ann-Sofie Johansson, Panagiotis Georgiadis, Beatrice Melin, Domenico Palli, Vittorio Krogh, Salvatore Panico, Carlotta Sacerdote, Rosario Tumino, Paolo Vineis, Raphaële Castagné, Marc Chadeau-Hyam
Recent prospective studies have shown that dysregulation of the immune system may precede the development of B-cell lymphomas (BCL) in immunocompetent individuals. However, to date, the studies were restricted to a few immune markers, which were considered separately. Using a nested case-control study within two European prospective cohorts, we measured plasma levels of 28 immune markers in samples collected a median of 6 years prior to diagnosis (range, 2.01-15.97) in 268 incident cases of BCL (including multiple myeloma) and matched controls...
April 18, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29567785/dna-polymerase-%C3%AE-gene-expression-influences-fludarabine-resistance-in-chronic-lymphocytic-leukemia-independently-from-p53-status
#9
Srdana Grgurevic, Patricia Montilla-Perez, Alice Bradbury, Julia Gilhodes, Sophie Queille, Sandrine Pelofy, Aurélien Bancaud, Thomas Filleron, Loïc Ysebaert, Christian Récher, Guy Laurent, Jean-Jacques Fournié, Christophe Cazaux, Anne Quillet-Mary, Jean-Sébastien Hoffmann
Alteration in the DNA Replication, Repair or Recombination processes is a highly relevant mechanism of genomic instability. Despite genomic aberrations manifested in haematological malignancies, such a defect as a source of biomarkers has been underexplored. Here, we investigated prognostic value of expression of 82 genes involved in DNA Replication-Repair-Recombination in a series of 99 patients with chronic lymphocytic leukaemia without detected 17p deletion or TP53 mutation. We unveiled that expression of the POLN gene, encoding the specialized DNA polymerase ν (Polν) correlates with time to relapse after the first-line therapy with fludarabine...
March 22, 2018: Haematologica
https://www.readbyqxmd.com/read/29504446/the-clinical-significance-of-b-cell-maturation-antigen-as-a-therapeutic-target-and-biomarker
#10
Eric Sanchez, Edward J Tanenbaum, Saurabh Patil, Mingjie Li, Camilia M Soof, Aleksandra Vidisheva, Gabriel N Waterman, Tara Hekmati, George Tang, Cathy S Wang, Haiming Chen, James Berenson
B-cell maturation antigen (BCMA) is a cell membrane bound tumor necrosis factor receptor family member that is expressed exclusively on late stage normal and malignant B-cells and plasma cells. Addition of two of its ligands, B-cell activating factor and a proliferation inducting ligand, to normal B-cells cause B-cell proliferation and antibody production. Serum BCMA is elevated among patients with multiple myeloma (MM) and chronic lymphocytic leukemia (CLL), and is a prognostic and monitoring tool for these patients...
April 2018: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/29450576/immunopet-imaging-of-cd38-in-murine-lymphoma-models-using-89-zr-labeled-daratumumab
#11
Lei Kang, Dawei Jiang, Christopher G England, Todd E Barnhart, Bo Yu, Zachary T Rosenkrans, Rongfu Wang, Jonathan W Engle, Xiaojie Xu, Peng Huang, Weibo Cai
PURPOSE: CD38 is considered a potential biomarker for multiple myeloma (MM) and has shown a strong link with chronic lymphocytic leukemia due to high and uniform expression on plasma cells. In vivo evaluation of CD38 expression may provide useful information about lesion detection and prognosis of treatment in MM. In this study, immunoPET imaging with 89 Zr-labeled daratumumab was used for differentiation of CD38 expression in murine lymphoma models to provide a potential non-invasive method for monitoring CD38 in the clinic...
February 15, 2018: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/29440231/-ex-vivo-activity-of-cytotoxic-drugs-and-targeted-agents-in-small-intestinal-neuroendocrine-tumors
#12
Kosmas Daskalakis, Olov Norlén, Andreas Karakatsanis, Per Hellman, Rolf Larsson, Peter Nygren, Peter Stålberg
Small intestinal neuroendocrine tumors (SI-NETs) are generally considered resistant to systemic treatment. To date, predictive markers for drug activity are lacking. Tumor samples from 27 patients with SI-NETs were analyzed ex vivo for sensitivity to a panel of cytotoxic drugs and targeted agents using a short-term total cell kill assay. Samples of renal cancer, colorectal cancer (CRC), ovarian cancer and chronic lymphocytic leukemia (CLL) were included for comparison. For the SI-NET subset, drug sensitivity was analyzed in relation to clinicopathological variables and pre-treatment biomarkers...
April 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29394974/proteomic-profile-of-lymphoid-leukemia
#13
Amer Abdulrahman Almaiman
Lymphoid (or lymphocytic/lymphoblastic) leukemia, one of two major types of leukemias (lymphoid and myeloid), is divided into two subtypes, acute lymphoid leukemia (ALL) and chronic lymphocytic leukemia (CLL), depending on the maturation stage and speed of multiplication of the bone marrow lymphocytes. Early diagnosis and treatment can make the difference between life and death. Advancements in the field of proteomics may allow the development of early biomarkers and more effective agents to combat both these types of cancer, and to better understand the underlying mechanisms of the disease...
February 2018: Journal of the College of Physicians and Surgeons—Pakistan: JCPSP
https://www.readbyqxmd.com/read/29371889/cytogenetic-mutation-profile-of-chronic-lymphocytic-leukemia-malignant-melanoma-collision-tumors-of-the-skin
#14
Roberta La Starza, Tiziana Pierini, Lorenza Pastorino, Elisa Albi, Caterina Matteucci, Barbara Crescenzi, Paolo Sportoletti, Piero Covarelli, Franca Falzetti, Giovanni Roti, Stefano Ascani, Cristina Mecucci
Background: Collision tumors are rare entities that consist of two histologically distinct tumor types arising in the same anatomic site. An association between chronic lymphocytic leukemia (CLL) and malignant melanoma (MM) has been already described. Up to now, they have been documented only at positive regional lymph nodes while we focused on collision tumor in a skin lesion. Case presentation: We characterized the genomic profile of a skin CLL/MM collision tumor in a patient with a 9-years story of CLL...
2018: Molecular Cytogenetics
https://www.readbyqxmd.com/read/29360924/neopepsee-accurate-genome-level-prediction-of-neoantigens-by-harnessing-sequence-and-amino-acid-immunogenicity-information
#15
S Kim, H S Kim, E Kim, M G Lee, E Shin, S Paik, S Kim
Background: Tumor-specific mutations form novel immunogenic peptides called neoantigens. Neoantigens can be used as a biomarker predicting patient response to cancer immunotherapy. Although a predicted binding affinity (IC50) between peptide and major histocompatibility complex class I (MHC-I) is currently used for neoantigen prediction, large number of false-positives exist. Materials and methods: We developed Neopepsee, a machine learning-based neoantigen prediction program for next-generation sequencing data...
January 19, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29317636/the-expression-of-inhibitor-of-bruton-s-tyrosine-kinase-gene-is-progressively-up-regulated-in-the-clinical-course-of-chronic-lymphocytic-leukaemia-conferring-resistance-to-apoptosis
#16
Francesco Albano, Federico Chiurazzi, Selena Mimmi, Eleonora Vecchio, Arianna Pastore, Clementina Cimmino, Camilla Frieri, Enrico Iaccino, Antonio Pisano, Gaetanina Golino, Giuseppe Fiume, Massimo Mallardo, Giuseppe Scala, Ileana Quinto
Chronic lymphocytic leukaemia (CLL) is the most common B-cell malignancy with a variable clinical outcome. Biomarkers of CLL progression are required for optimising prognosis and therapy. The Inhibitor of Bruton's tyrosine kinase-isoform α (IBTKα) gene encodes a substrate receptor of Cullin 3-dependent E3 ubiquitin ligase, and promotes cell survival in response to the reticulum stress. Searching for novel markers of CLL progression, we analysed the expression of IBTKα in the peripheral blood B-cells of CLL patients, before and after first line therapy causing remission...
January 9, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29227286/drug-perturbation-based-stratification-of-blood-cancer
#17
Sascha Dietrich, Małgorzata Oleś, Junyan Lu, Leopold Sellner, Simon Anders, Britta Velten, Bian Wu, Jennifer Hüllein, Michelle da Silva Liberio, Tatjana Walther, Lena Wagner, Sophie Rabe, Sonja Ghidelli-Disse, Marcus Bantscheff, Andrzej K Oleś, Mikołaj Słabicki, Andreas Mock, Christopher C Oakes, Shihui Wang, Sina Oppermann, Marina Lukas, Vladislav Kim, Martin Sill, Axel Benner, Anna Jauch, Lesley Ann Sutton, Emma Young, Richard Rosenquist, Xiyang Liu, Alexander Jethwa, Kwang Seok Lee, Joe Lewis, Kerstin Putzker, Christoph Lutz, Davide Rossi, Andriy Mokhir, Thomas Oellerich, Katja Zirlik, Marco Herling, Florence Nguyen-Khac, Christoph Plass, Emma Andersson, Satu Mustjoki, Christof von Kalle, Anthony D Ho, Manfred Hensel, Jan Dürig, Ingo Ringshausen, Marc Zapatka, Wolfgang Huber, Thorsten Zenz
As new generations of targeted therapies emerge and tumor genome sequencing discovers increasingly comprehensive mutation repertoires, the functional relationships of mutations to tumor phenotypes remain largely unknown. Here, we measured ex vivo sensitivity of 246 blood cancers to 63 drugs alongside genome, transcriptome, and DNA methylome analysis to understand determinants of drug response. We assembled a primary blood cancer cell encyclopedia data set that revealed disease-specific sensitivities for each cancer...
January 2, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29222275/the-mutational-landscape-of-chronic-lymphocytic-leukemia-and-its-impact-on-prognosis-and-treatment
#18
REVIEW
Gianluca Gaidano, Davide Rossi
The typical genome of chronic lymphocytic leukemia (CLL) carries ∼2000 molecular lesions. Few mutations recur across patients at a frequency >5%, whereas a large number of biologically and clinically uncharacterized genes are mutated at lower frequency. Approximately 80% of CLL patients carry at least 1 of 4 common chromosomal alterations, namely deletion 13q14, deletion 11q22-23, deletion 17p12, and trisomy 12. Knowledge of the CLL genome has translated into the availability of molecular biomarkers for prognosis and treatment prediction...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29157092/single-agent-and-synergistic-combinatorial-efficacy-of-first-in-class-small-molecule-imipridone-onc201-in-hematological-malignancies
#19
Varun V Prabhu, Mala K Talekar, Amriti R Lulla, C Leah B Kline, Lanlan Zhou, Junior Hall, A Pieter J Van den Heuvel, David T Dicker, Jawad Babar, Stephan A Grupp, Mathew J Garnett, Ultan McDermott, Cyril H Benes, Jeffrey J Pu, David F Claxton, Nadia Khan, Wolfgang Oster, Joshua E Allen, Wafik S El-Deiry
ONC201, founding member of the imipridone class of small molecules, is currently being evaluated in advancer cancer clinical trials. We explored single agent and combinatorial efficacy of ONC201 in preclinical models of hematological malignancies. ONC201 demonstrated (GI50 1-8 µM) dose- and time-dependent efficacy in acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML), chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), Burkitt's lymphoma, anaplastic large cell lymphoma (ALCL), cutaneous T-cell lymphoma (CTCL), Hodgkin's lymphoma (nodular sclerosis) and multiple myeloma (MM) cell lines including cells resistant to standard of care (dexamethasone in MM) and primary samples...
2018: Cell Cycle
https://www.readbyqxmd.com/read/29118007/pd-1-expression-and-clinical-pd-1-blockade-in-b-cell-lymphomas
#20
REVIEW
Zijun Y Xu-Monette, Jianfeng Zhou, Ken H Young
Programmed cell death protein 1 (PD-1) blockade targeting the PD-1 immune checkpoint has demonstrated unprecedented clinical efficacy in the treatment of advanced cancers including hematologic malignancies. This article reviews the landscape of PD-1/programmed death-ligand 1 (PD-L1) expression and current PD-1 blockade immunotherapy trials in B-cell lymphomas. Most notably, in relapsed/refractory classical Hodgkin lymphoma, which frequently has increased PD-1+ tumor-infiltrating T cells, 9p24.1 genetic alteration, and high PD-L1 expression, anti-PD-1 monotherapy has demonstrated remarkable objective response rates (ORRs) of 65% to 87% and durable disease control in phase 1/2 clinical trials...
January 4, 2018: Blood
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