Search results for "Chronic Lymphocytic Leukemia"
showing 10 items of 93 documents
The cumulative amount of serum-free light chain is a strong prognosticator in chronic lymphocytic leukemia.
2011
AbstractIdentification of patients at risk of early disease progression is the mainstay of tailored management in chronic lymphocytic leukemia (CLL). Although application of established biomarkers is limited by intrinsic detection/readout complexities, abnormality of κ and λ serum-free light chain ratio [sFLC (κ/λ)] was proposed as a straightforward prognosticator in CLL. By analyzing 449 therapy-naive patients, we show that an abnormal sFLC(κ/λ), along with CD38, ZAP-70, IGHV mutations, cytogenetics and stage, independently predicts treatment-free survival (TFS) but becomes prognostically irrelevant if the cumulative amount of clonal and nonclonal FLCs [sFLC(κ + λ)], a variable associated …
Increased Oxidative Damage Associated with Unfavorable Cytogenetic Subgroups in Chronic Lymphocytic Leukemia
2014
Oxidative stress contributes to genomic instability in chronic lymphocytic leukemia (CLL), but its relationship with the acquisition of specific chromosomal abnormalities is unknown. We recruited 55 untreated CLL patients and assessed 8-oxo-2′-deoxyguanosine (8-oxo-dG), glutathione, and malondialdehyde (MDA) levels, and we compared them among the cytogenetic subgroups established using fluorescence in situ hybridization (FISH). Significant increases in 8-oxo-dG and/or MDA were observed in patients with unfavorable cytogenetic aberrations (17p and 11q deletions) compared to the 13q deletion group.TP53deletion patients exhibited a diminished DNA repair efficiency. Finally, cases with normal F…
Baseline Characteristics Predicting Very Good Outcome of Allogeneic Hematopoietic Cell Transplantation in Young Patients With High Cytogenetic Risk C…
2017
Patients with chronic lymphocytic leukemia with del(17p) or del(11q) have poor long-term prognosis with targeted therapies. Conversely, this retrospective European Society for Blood and Marrow Transplantation registry study shows that young high cytogenetic risk responsive patients with human leukocyte antigen-matched donors have a high 8-year progression-free survival and low 2-year non-relapse mortality after allogeneic stem cell transplantation. This treatment then may compare favorably with targeted therapies for younger high cytogenetic risk patients.Background: Patients with genetically high-risk relapsed/refractory chronic lymphocytic leukemia have shorter median progression-free sur…
Identification of novel, clonally stable, somatic mutations targeting transcription factors PAX5 and NKX2-3, the epigenetic regulator LRIF1, and BRAF…
2021
Diagnosis of B-cell chronic lymphocytic leukemia (B-CLL) is usually straightforward, involving clinical, immunophenotypic (Matutes score), and (immuno)genetic analyses (to refine patient prognosis for treatment). CLL cases with atypical presentation (e.g., Matutes ≤ 3) are also encountered, and for these diseases, biology and prognostic impact are less clear. Here we report the genomic characterization of a case of atypical B-CLL in a 70-yr-old male patient; B-CLL cells showed a Matutes score of 3, chromosomal translocation t(14;18)(q32;q21) (BCL2/IGH), mutated IGHV, deletion 17p, and mutations in BCL2, NOTCH1 (subclonal), and TP53 (subclonal). Quite strikingly, a novel PAX5 mutation that w…
Antioxidant enzyme activities and the production of MDA and 8-oxo-dG in chronic lymphocytic leukemia.
2001
Abstract Chronic lymphocytic leukemia (CLL) is a neoplastic disease susceptible to antioxidant enzyme alterations and oxidative stress. We have examined the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), and the oxidized/reduced glutathione (GSSG/GSH) ratio together with the levels of malondialdehyde (MDA) and 8-oxo-2′-deoxyguanosine (8-oxo-dG) in lymphocytes of CLL patients and compared them with those of normal subjects of the same age. SOD and CAT activity decreased in CLL lymphocytes while GPx activity increased. GSH content of CLL lymphocytes also increased, and GSSG concentration remained constant. Thus, a reduced GSSG/GSH ratio was obtaine…
Chemoimmunotherapy with O-FC in previously untreated patients with chronic lymphocytic leukemia
2011
We conducted an international phase 2 trial to evaluate 2 dose levels of ofatumumab, a human CD20 mAb, combined with fludarabine and cyclophosphamide (O-FC) as frontline therapy for chronic lymphocytic leukemia (CLL). Patients with active CLL were randomized to ofatumumab 500 mg (n = 31) or 1000 mg (n = 30) day 1, with fludarabine 25 mg/m2 and cyclophosphamide 250 mg/m2 days 2-4, course 1; days 1-3, courses 2-6; every 4 weeks for 6 courses. The first ofatumumab dose was 300 mg for both cohorts. The median age was 56 years; 13% of patients had a 17p deletion; 64% had β2-microglobulin > 3.5 mg/L. Based on the 1996 National Cancer Institute Working Group (NCI-WG) guidelines, the complete respo…
MiR-146b-5p regulates IL-23 receptor complex expression in chronic lymphocytic leukemia cells
2022
Abstract Chronic lymphocytic leukemia (CLL) cells express the interleukin-23 receptor (IL-23R) chain, but the expression of the complementary IL-12Rβ1 chain requires cell stimulation via surface CD40 molecules (and not via the B-cell receptor [BCR]). This stimulation induces the expression of a heterodimeric functional IL-23R complex and the secretion of IL-23, initiating an autocrine loop that drives leukemic cell expansion. Based on the observation in 224 untreated Binet stage A patients that the cases with the lowest miR-146b-5p concentrations had the shortest time to first treatment (TTFT), we hypothesized that miR-146b-5p could negatively regulate IL-12Rβ1 side chain expression and clo…
Sepsis due to Erysipelothrix rhusiopathiae in a Patient with Chronic Lymphocytic Leukemia Associated with Bronchopneumonia due to PSeudomonas aerugin…
2015
Erysipelothrix rhusiopathiae infections can typically be attributed to exposure to animal products; thus, these infections are more common among farmers, butchers and veterinarians, among others. This article describes a case involving a 54-year-old man who had relative neutropenia subsequent to treatment for chronic lymphocytic leukemia. The patient developed E rhusiopathiae bacteremia with concomitant pneumonia. The author of this article suggests a likely route of infection, which is atypical considering the patient did not report exposure to animal products.
Defective stromal remodeling and neutrophil extracellular traps in lymphoid tissues favor the transition from autoimmunity to lymphoma
2013
Abstract Altered expression of matricellular proteins can become pathogenic in the presence of persistent perturbations in tissue homeostasis. Here, we show that autoimmunity associated with Fas mutation was exacerbated and transitioned to lymphomagenesis in the absence of SPARC (secreted protein acidic rich in cysteine). The absence of SPARC resulted in defective collagen assembly, with uneven compartmentalization of lymphoid and myeloid populations within secondary lymphoid organs (SLO), and faulty delivery of inhibitory signals from the extracellular matrix. These conditions promoted aberrant interactions between neutrophil extracellular traps and CD5+ B cells, which underwent malignant …
Proteomic Profile Study of Chronic Lymphocytic Leukemia-B Patients with IGVH and BCL6 Mutated or Unmutated Genes.
2004
Abstract Introduction: Chronic lymphocytic leukemia B (CLL-B) is the most frequent chronic lymphoproliferative disorder in western countries. The majority of patients are diagnosed in incipient Binet stage A. Some prognostic factors have been identified, as mutations in the genes coding for immunoglobulin variable regions (IgVH). Complementary somatic mutations in the BCL6 gene have been observed in 25% of CLL-B patients, although its clinical relevance remains unclear. Objective: To identify molecular markers of different patient groups of lymphoproliferative disorder through analysis of their proteomic profiles. Material and Methods: 15 samples of peripheral blood lymphocytes B from Binet…