Search results for "Chronic Lymphocytic Leukemia"
showing 10 items of 93 documents
Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia
2013
Genome-wide association studies (GWAS) have previously identified 13 loci associated with risk of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL). To identify additional CLL susceptibility loci, we conducted the largest meta-analysis for CLL thus far, including four GWAS with a total of 3,100 individuals with CLL (cases) and 7,667 controls. In the meta-analysis, we identified ten independent associated SNPs in nine new loci at 10q23.31 (ACTA2 or FAS (ACTA2/FAS), P = 1.22 × 10-14), 18q21.33 (BCL2, P = 7.76 × 10-11), 11p15.5 (C11orf21, P = 2.15 × 10 -10), 4q25 (LEF1, P = 4.24 × 10-10), 2q33.1 (CASP10 or CASP8 (CASP10/CASP8), P = 2.50 × 10-9), 9p21.3 (CDKN2B-AS1, P = 1.27 × 10…
Chronic lymphocytic leukemia nurse-like cells express hepatocyte growth factor receptor (c-MET) and indoleamine 2,3-dioxygenase and display features …
2014
Hepatocyte growth factor, produced by stromal and follicular dendritic cells, and present at high concentrations in the sera of patients with chronic lymphocytic leukemia, prolongs the survival of leukemic B cells by interacting with their receptor, c-MET. It is, however, unknown whether hepatocyte growth factor influences microenvironmental cells, such as nurse-like cells, which deliver survival signals to the leukemic clone. We evaluated the expression of c-MET on nurse-like cells and monocytes from patients with chronic lymphocytic leukemia and searched for phenotypic/functional features supposed to be influenced by the hepatocyte growth factor/c-MET interaction. c-MET is expressed at hi…
CCL3 and CCL4, the Major Chemokines Produced by CD38+ Chronic Lymphocytic Leukemia Cells, Facilitate Microenvironmental Interactions of Neoplastic Ce…
2008
Abstract CD38, a negative prognostic marker for patients with CLL, has been demonstrated to be a key molecule in the interactions occurring in the context of tumor microenvironment, mediating both survival and migratory signals for CLL cells. By taking advantage of gene expression profiling studies (GEP) comparing 11 CD38pos (CD38>30%) and 15 CD38neg (CD38<10%) CLLs, we identified as over-expressed in CD38pos CLL cells: i) genes for the two C-C chemokines CCL3 and CCL4 (median-log difference, MLD-CCL3= 3.5; MLD-CCL4=4.4); real-time quantitative PCR (RTQ-PCR) of selected cases confirmed GEP results; ii) the gene for CD49d (MLD=4.4); a high correlation between CD38 and CD49d pro…
NFATc1 Is Transcriptionally Activated in Chronic Lymphocytic Leukemia (CLL) By Promotor DNA-Hypomethylation Which Correlates with in-Vitro Vulnerabil…
2014
Abstract Chronic lymphocytic leukemia (CLL), the most frequent adult leukemia in Western countries, is characterized by progressive accumulation of mature, monoclonal B lymphocytes in blood, bone marrow, and lymphoid tissues. In the pathogenesis and treatment of CLL, B cell receptor (BCR) signaling plays a crucial role, and aberrations in downstream pathways that become activated in CLL need to be better defined. One downstream target of BCR signaling is NFATc1, a transcription factor with a high oncogenic and transforming potential. Employing a genome-wide comparative DNA methylation analysis the NFATc1 5’ region was identified to be DNA hypomethylated in CLL patient samples. The pilot ser…
Detection of Immunoglobulin Heavy Chain Gene Clonality By High-Throughput Sequencing for Minimal Residual Disease Monitoring in Chronic Lymphocytic L…
2019
Introduction: The negative minimal residual disease (MRD) after treatment has been recently accepted as endpoint for Chronic Lymphocytic Leukaemia (CLL) clinical trials. Conventionally, MRD can be detected by using multi-color Flow Cytometry (FC) with high sensitivity. Determination of the clonal immunoglobulin gene rearrangement can be a useful monitoring marker in a broad range of B-cell lymphoproliferative neoplasms. Moreover, the mutational status of immunoglobulin heavy chain variable (IgHV) rearrangement is considered one of the most important prognostic factors in CLL. Therefore, the identification of the IgHV rearrangement can be a useful marker both at diagnostic and as monitoring …
CD49d Expression Identifies a Chronic Lymphocytic Leukemia (CLL) Subset with High Levels of Circulating CD34 +Cells Co-Expressing Endothelial Cell Ma…
2009
Abstract Abstract 2329 Poster Board II-306 Introduction: In chronic lymphocytic leukemia (CLL), CD49d, often in association with CD38, has been shown to mark a disease subset with poor prognosis. Functionally, both molecules act as counter-receptors for surface structures (i.e. VCAM-1/CD106 and CD31) usually expressed by the endothelial/stromal component of tumor micro-environment. We have recently identified a micro-environmental circuitry which involves CD38 triggering, and eventually determines an enrichment of the VCAM-1/CD106-expressing endothelial component detected in the context of CLL infiltrates found in bone marrow biopsies. Data was also provided that CD49d/VCAM-1 interactions a…
Angiopoietin-2 plasma dosage predicts time to first treatment and overall survival in chronic lymphocytic leukemia.
2010
Abstract The clinical relevance of angiopoietin-2 (Ang2) in chronic lymphocytic leukemia (CLL) was previously suggested by the association between high Ang2, and shorter progression-free survival reported in small series of patients. Here, we evaluated Ang2 glycoprotein levels in plasma samples collected from a multicentric cohort of CLL patients (n = 316) using an enzyme-linked immunosorbent assay method, and we investigated its prognostic role in relation to time to first treatment (TTFT) and overall survival. Based on a cutoff equal to 2459 pg/mL, we divided our cohort in 2 subsets (high and low Ang2) composing 100 (31.6%) and 216 (68.4%) patients, respectively. High Ang2 was predictive …
Molecular Remission Can Be Attained in Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL) and Follicular Lymphomas after Reduced Intensity Con…
2004
Abstract RIC followed by allo-SCT is an effective salvage treatment for some relapsed hematologic malignancies due to the postulated graft versus tumour (GVT) effect. In order to evaluate the quality of the clinical response, we have investigated the molecular status of patients receiving allo-SCT for relapsed disease. Forty-four patients (19 chronic lymphocytic leukemias (CLL), 21 follicular lymphomas (FCL) and 4 small lymphocytic lymphomas (SLL)) were enrolled in a prospective phase II study. The median age was 54 years (range: 32–69 years). The median number of previous chemotherapy regimens was 2 (range: 1–5) and 23% of patients had already failed an auto-SCT. Before transplant 34% of p…
High-Dose Therapy and Autologous Hematopoietic Stem Cell Transplantation (ASCT) Has a Significant but Transient Impact on Quality of Life: Lessons Fr…
2011
Abstract Abstract 1989 Objective: High-dose therapy (HDT) and ASCT is the standard of care in a variety of hematologic malignancies. Whereas for some indications a survival advantage for HDT and ASCT has been demonstrated, a benefit only in terms of better progression-free survival has been shown for CLL. Because of this the quality of life (QoL) deserves particular attention. QoL assessment was a major focus of a randomized controlled EBMT-Intergroup trial on the value of HDT compared to observation in first or second remission of CLL (Michallet, Blood, 2011). Methods: 222 patients were enrolled into the study and allocated to either ASCT or observation. In the transplant arm, 72% received…
Outcomes of Mismatched Related Allogeneic Stem Cell Transplantation for Chronic Lymphocytic Leukemia: A Retrospective Study on Behalf of the Chronic …
2016
Abstract Introduction: Allogeneic hematopoietic stem cell transplantation (HCT) is a treatment for CLL that can give long disease control. Even with the availability of kinase and BCL2 inhibitors, HCT is still performed in fit patients (pts) with high-risk CLL. Almost exclusively, outcomes on matched related and unrelated donor transplantations in CLL have been published. Recently, mismatched related donors are gaining interest because of the better outcome of haploidentical HCT with post-transplantation cyclophosphamide (PTCY). Methods: All pts with CLL who received a first allogeneic HCT with a mismatched related donor and whose data were available in the EBMT registry were analyzed. Medi…