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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...
March 7, 2018: Expert Review of Molecular Diagnostics
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 with89 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
Kosmas Daskalakis, Olov Norlen, Andreas Karakatsanis, Per Hellman, Rolf Larsson, Peter Nygren, Peter Stalberg
Small intestinal endocrine tumours (SI-NETs) are generally considered resistant to systemic treatment. To date, predictive markers for drug activity are lacking. Tumour 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 clinico-pathological variables and pre-treatment biomarkers...
February 12, 2018: Endocrine-related Cancer
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
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
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
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
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
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
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...
November 20, 2017: Cell Cycle
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
Ayed O Ayed, Sameer A Parikh
The past two decades have witnessed a paradigm shift in the management of patients with chronic lymphocytic leukemia (CLL), particularly with the introduction of targeted therapies to clinical practice. Ibrutinib is an irreversible inhibitor of Bruton's tyrosine kinase (BTK) and has shown significant efficacy and tolerability, even in heavily treated patients. Despite improvement in outcomes, patients do ultimately relapse. Those who develop disease progression on ibrutinib are a particularly high-risk population with poor outcomes...
November 8, 2017: Leukemia & Lymphoma
Saeid Taghiloo, Esmaeil Allahmoradi, Reza Ebadi, Mohsen Tehrani, Zahra Hosseini-Khah, Ghasem Janbabaei, Ramin Shekarriz, Hossein Asgarian-Omran
Background: Deviation of host immune response by engagement of inhibitory receptors is one of the well-known mechanisms of tumor cells for immune evasion and survival. PD-1/PD-L1 and Tim-3/Gal-9 axes are two major pathways in this area which their contribution has been documented in a variety of malignancies. In this study, Gal-9 and PD-L1 expression was investigated in leukemic cells from patients with Chronic Lymphocytic Leukemia (CLL). Methods: Peripheral blood mononuclear cells (PBMCs) were obtained from 25 untreated CLL patients and 15 sex- and age-matched healthy controls...
August 27, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
Alexander W MacFarlane, Mowafaq Jillab, Mitchell R Smith, R Katherine Alpaugh, Marion E Cole, Samuel Litwin, Michael M Millenson, Tahseen Al-Saleem, Adam D Cohen, Kerry S Campbell
A prospective analysis of natural killer (NK) cell phenotype and function was performed on fresh peripheral blood samples from untreated patients with B-cell chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Compared to healthy controls, CD56(dim) NK cells in CLL patients displayed reduced expression of the NKG2D activating receptor and increased CD27 expression, which indicates declines in mature cells. In addition, NK cells from CLL patients showed reduced degranulation responses toward transformed B cells alone or with rituximab and were more sensitive to activation-induced cell death...
2017: Oncoimmunology
Yunfeng Zhang, Jinbo Lin, Wenjie Huang, Yong Cao, Yi Liu, Tieqiang Wang, Weiyi Zhong, Dongli Wang, Rongrong Mao, Xiaoliang Chen
PURPOSE: Abnormal expression of miR-223 in cancerous tissue has confirmed it as an important player in tumorigenesis of cancers, such as hepatocellular carcinoma, colorectal carcinoma, osteosarcoma, gastric cancer, and chronic lymphocytic leukemia. The present meta-analysis aimed to explore the association between circulating miR-223 and prognosis of cancers. METHODS: The studies were accessed by an electronic search of multiple databases. RevMan5.3 and STATA14...
2017: OncoTargets and Therapy
Larion Santiago, Garrett Daniels, Dongwen Wang, Fang-Ming Deng, Peng Lee
Transcription factors are regulatory proteins that either activate or repress the transcription of genes via binding to DNA regulatory sequences and regulating recruitment of transcriptional complexes. Lymphoid enhancer-binding factor 1 (LEF1), a member of the T-cell Factor (TCF)/LEF1 family of high-mobility group transcription factors, is a downstream mediator of the Wnt/β-catenin signaling pathway, but can also modulate gene transcription independently. LEF1 is essential in stem cell maintenance and organ development, especially in its role in epithelial-mesenchymal transition (EMT) by activating the transcription of hallmark EMT effectors including N-Cadherin, Vimentin, and Snail...
2017: American Journal of Cancer Research
Arantza Onaindia, L Jeffrey Medeiros, Keyur P Patel
Genomic profiling studies have provided new insights into the pathogenesis of mature B-cell neoplasms and have identified markers with prognostic impact. Recurrent mutations in tumor-suppressor genes (TP53, BIRC3, ATM), and common signaling pathways, such as the B-cell receptor (CD79A, CD79B, CARD11, TCF3, ID3), Toll-like receptor (MYD88), NOTCH (NOTCH1/2), nuclear factor-κB, and mitogen activated kinase signaling, have been identified in B-cell neoplasms. Chronic lymphocytic leukemia/small lymphocytic lymphoma, diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, Burkitt lymphoma, Waldenström macroglobulinemia, hairy cell leukemia, and marginal zone lymphomas of splenic, nodal, and extranodal types represent examples of B-cell neoplasms in which novel molecular biomarkers have been discovered in recent years...
October 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Kadry M Sadek, Mohamed A Lebda, Tarek K Abouzed, Sherif M Nasr, Moustafa Shoukry
Cadmium (Cd) exposure leads to production of reactive oxygen species (ROS), which are associated with Cd-induced neurotoxicity and nephrotoxicity. Selenium nanoparticles (Se-NPs) have high bioavailability and antioxidant activities so it attracted wide spread attention. The present study examined the possible ameliorative effect of Se-NPs with diameters of 3-5 nm and 10-20 nm against cadmium chloride (CdCl2)-induced neuro- and nephrotoxicity in rats. Rats were treated with Se-NPs (0 or 0.5 mg/kg BW, s.c...
June 28, 2017: Metabolic Brain Disease
Tatiane Vieira Braga, Fernanda Cristina Gontijo Evangelista, Lorena Caixeta Gomes, Sérgio Schusterschitz da Silva Araújo, Maria das Graças Carvalho, Adriano de Paula Sabino
Chronic lymphocytic leukemia (CLL) is a B lineage neoplasm, characterized by the accumulation of B lymphocytes of great longevity, and usually develops as a result of the inhibition of apoptosis. Clinical evolution is extremely variable amongst affected individuals with survival ranging from a few months in aggressive cases, to a few decades in cases of indolent CLL. The identification of new prognostic factors, apart from clinical staging, has been an important research topic aiming at a better understanding of CLL...
August 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Jennifer Crombie, Matthew S Davids
As the therapeutic landscape for chronic lymphocytic leukemia (CLL) continues to expand, biological predictors of response to therapy are becoming increasingly important. One such predictive biomarker is the mutational status of the variable region of the immunoglobulin heavy chain (IGHV) gene, which is a powerful predictor of duration of response and overall survival with chemoimmunotherapy (CIT). As this test may influence choice of therapy between CIT and novel agents, it is critical that providers understand how mutational status is determined and the limitations of testing...
December 2017: American Journal of Hematology
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