A5026162080- Chronic Lymphocytic Leukemia Research
- Immunodeficiency and Autoimmune Disorders
- Lymphoma Diagnosis and Treatment
- Immune Cell Function and Interaction
- Monoclonal and Polyclonal Antibodies Research
- Glycosylation and Glycoproteins Research
- Galectins and Cancer Biology
- Acute Myeloid Leukemia Research
- Bioinformatics and Genomic Networks
- Immune Response and Inflammation
- RNA modifications and cancer
- Advanced Breast Cancer Therapies
- Cancer Genomics and Diagnostics
- Diabetes Treatment and Management
- Acute Lymphoblastic Leukemia research
- Epigenetics and DNA Methylation
- NF-κB Signaling Pathways
- Neuroendocrine Tumor Research Advances
- Genetic factors in colorectal cancer
- Viral-associated cancers and disorders
- Phagocytosis and Immune Regulation
- Biological Research and Disease Studies
- Cancer Immunotherapy and Biomarkers
- Ubiquitin and proteasome pathways
- PI3K/AKT/mTOR signaling in cancer
Centre for Research and Technology Hellas
2013-2022
Rabin Medical Center
2019
Uppsala University
2016-2018
Science for Life Laboratory
2016-2018
G. Papanikolaou General Hospital
2012-2016
China Philanthropy Research Institute
2013
Hellenic Agency for Local Development and Local Government
2013
National and Kapodistrian University of Athens
2010-2012
Aristotle University of Thessaloniki
2011
Abstract Cell-autonomous B-cell receptor (BcR)-mediated signalling is a hallmark feature of the neoplastic B lymphocytes in chronic lymphocytic leukaemia (CLL). Here we elucidate structural basis autonomous activation CLL cells, showing that BcR immunoglobulins initiate intracellular through homotypic interactions between epitopes are specific for each subgroup patients with homogeneous clinicobiological profiles. The molecular details BcR–BcR apparently dictate clinical course disease,...
Background Signaling through the B-cell receptor appears to be a major contributor pathogenesis of chronic lymphocytic leukemia. Toll-like receptors bridge innate and adaptive immune responses by acting as co-stimulatory signals for B cells. The available data on expression in leukemia are limited derive from small series patients.Design Methods We profiled genes associated with signaling pathways 192 cases explored potential associations molecular features clonotypic receptors.Results...
Histone methyltransferases (HMTs) are important epigenetic regulators of gene transcription and disrupted at the genomic level in a spectrum human tumours including haematological malignancies. Using high-resolution single nucleotide polymorphism (SNP) arrays, we identified recurrent deletions SETD2 locus 3% (8/261) chronic lymphocytic leukaemia (CLL) patients. Further validation two independent cohorts showed that were associated with loss TP53, complexity chromothripsis. With...
Subgroups of patients with chronic lymphocytic leukemia (CLL) have distinct expression profiles Toll-like receptor (TLR) pathway-associated genes. To test the hypothesis that signaling through innate immunity receptors may influence behavior malignant clone, we investigated functional response triggered by stimulation TLRs and NOD2 in 67 CLL cases assigned to different subgroups on basis immunoglobulin heavy variable (IGHV) gene usage, IGHV mutational status or B-cell (BcR) stereotypy....
Abstract Critical processes of B-cell physiology, including immune signaling through the receptor (BcR) and/or Toll-like receptors (TLRs), are targeted by microRNAs. With this in mind and also given important role BcR TLR microRNAs chronic lymphocytic leukemia (CLL), we investigated whether could be implicated shaping behavior CLL clones with distinct molecular functional profiles. To end, examined 79 cases for expression 33 microRNAs, selected on following criteria: (a) deregulated versus...
The chromatin modifier EZH2 is overexpressed and associated with inferior outcome in mantle cell lymphoma (MCL). Recently, we demonstrated preferential DNA methylation of HOX genes MCL compared chronic lymphocytic leukemia (CLL), despite these not being expressed either entity. Since has been shown to regulate gene expression, gain further insight into its possible role differential silencing vs. CLL, performed detailed epigenetic characterization using representative lines primary samples....
Chronic lymphocytic leukemia (CLL) can be divided into prognostic subgroups based on the IGHV gene mutational status, and is further characterized by multiple subsets of cases with quasi-identical or stereotyped B cell receptors that also share clinical biological features. We recently reported differential DNA methylation profiles in IGHV-mutated IGHV-unmutated CLL subgroups. For first time, we here explore global different prognosis, applying high-resolution arrays samples from three major...
Purpose: We sought to investigate whether B cell receptor immunoglobulin (BcR IG) stereotypy is associated with particular clinicobiological features among chronic lymphocytic leukemia (CLL) patients expressing mutated BcR IG (M-CLL) encoded by the IGHV4-34 gene, and also ascertain these associations could refine prognostication.Experimental Design: In a series of 19,907 CLL cases available immunogenetic information, we identified 339 IGHV4-34-expressing assigned one four largest stereotyped...
// Nikos Papakonstantinou 1,2,* , Stavroula Ntoufa Elisavet Chartomatsidou 1 Konstantia Kotta Andreas Agathangelidis 3 Lefki Giassafaki Tzeni Karamanli Panagiota Bele Theodoros Moysiadis Panagiotis Baliakas 2 Lesley Ann Sutton Niki Stavroyianni 4 Achilles Anagnostopoulos Antonios M. Makris Paolo Ghia Richard Rosenquist and Kostas Stamatopoulos 1,2,4 Institute of Applied Biosciences, Center for Research Technology Hellas, Thessaloniki, Greece Department Immunology, Genetics Pathology, Science...
Abstract Chronic lymphocytic leukemia (CLL) patients assigned to stereotyped subset #4 (mutated IGHV4-34/IGKV2-30 BCR Ig) display a particularly indolent disease course. Immunogenetic studies of the clonotypic Ig CLL suggested resemblance with B cells rendered anergic through chronic autoantigenic stimulation. In this article, we provide experimental evidence that show low IgG levels, constitutive ERK1/2 activation, and fail either release intracellular Ca2+ or activate MAPK signaling after...
We recently reported that chronic lymphocytic leukemia (CLL) subgroups with distinct clonotypic BCRs present discrete patterns of TLR expression, function, and/or tolerance. In this study, to explore whether specific types BCR/TLR collaboration exist in CLL, we studied the effect single versus concomitant BCR stimulation on CLL cells from mutated (M-CLL) and unmutated (U-CLL) cases. stimulated negatively isolated by using anti-IgM, imiquimod, CpG oligodeoxynucleotide for BCR, TLR7, TLR9,...
Chronic lymphocytic leukemia (CLL) stereotyped subsets #6 and #8 include cases expressing unmutated B cell receptor immunoglobulin (BcR IG) (U-CLL). Subset (IGHV1-69/IGKV3-20) is less aggressive compared to subset (IGHV4-39/IGKV1(D)-39) which has the highest risk for Richter's transformation among all CLL. The underlying reasons this divergent clinical behavior are not fully elucidated. To gain insight into issue, here we focused on epigenomic signatures their links with gene expression,...
Recent studies of chronic lymphocytic leukemia (CLL) have reported recurrent mutations in the RPS15 gene, which encodes ribosomal protein S15 (RPS15), a component 40S subunit. Despite some evidence about role mutant (mostly obtained from analysis cell lines), precise impact on translational program primary CLL cells remains largely unexplored. Here, using RNA sequencing and ribosome profiling, technique that involves measuring efficiency, we sought to obtain global insight into changes...
Recent studies on splenic marginal zone lymphoma identified distinct mutations in genes belonging to the B-cell receptor and Toll-like signaling pathways, thus pointing their potential implication biology of disease. However, limited data is available regarding exact role TLRs. We aimed at characterizing expression pattern TLRs cells functional impact activation, proliferation viability malignant vitro. Cells expressed significant levels TLR1, TLR6, TLR7, TLR8, TLR9 TLR10 mRNA; TLR2 TLR4...
Key Points Microenvironmental stimuli affect EZH2 expression and function in CLL. Combined B-cell signaling inhibition showed synergistic effects on primary CLL cells.
Toll interleukin-1 receptor 8 (also known as TIR8, SIGIRR, or IL1R8) is a transmembrane that inhibits inflammation. Accordingly, genetic inactivation of this protein exacerbates chronic inflammation and inflammation-associated tumors in mice. In particular, lack TIR8 triggers leukemia progression mouse model lymphocytic (CLL), supporting its role novel tumor restrainer. The aim study was to measure the amount mRNA CLL cells, analyze regulation expression. Circulating leukemic cells expressed...
It has been proposed that vitamin D may play a role in prevention and treatment of cancer while epidemiological studies have linked insufficiency to adverse disease outcomes various B cell malignancies, including chronic lymphocytic leukemia (CLL). In this study, we sought obtain deeper biological insight into the its receptor (VDR) pathophysiology CLL. To end, performed expression analysis pathway molecules; complemented by RNA-Sequencing primary CLL cells were treated vitro with...