Fluorescence in situ hybridization analysis does not increase detection rate for trisomy 8 in chronic myelomonocytic leukemia.

Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell neoplasm characterized by overlapping myelodysplastic and myeloproliferative features. Diagnosis is based on persistent mo...

Increased Oxidative Damage Associated with Unfavorable Cytogenetic Subgroups in Chronic Lymphocytic Leukemia

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…

A retrospective analysis of myelodysplastic syndromes with thrombocytosis: reclassification of the cases by WHO proposals.

Myelodysplastic syndromes (MDS) show occasionally thrombocytosis, common feature of myeloproliferative diseases (MPD), with the overlapping of both disorders. Classically, thrombocytosis has been associated with some MDS subtypes: refractory anaemia with ringed sideroblasts (RARS), 5q- syndrome and those MDS with 3q chromosome rearrangements. The recent WHO classification recognises an unclassifiable MDS/MPD category including some of these disorders. Our aim is to determine the frequency of presentation, subtype classification and chromosome abnormalities of MDS with thrombocytosis diagnosed in our institution. Between 1990 and 2003 we studied 317 SMD patients according to FAB and WHO revi…

Prospective, Observational Study To Assess The Safety Of Rituximab In Combination With Chemotherapy In Patients With Previously-Untreated Or Relapsed Or Refractory B Cell-Lineage Chronic Lymphocytic Leukaemia (B-CLL): Preliminary Results

Abstract Aim and Background The efficacy and safety of rituximab plus chemo (R+chemo) for first-line and relapsed B-CLL patients(pts) have been widely investigated in clinical trials and large patient cohorts, but much less is known about whether such regimens can be effectively and safely administered to unselected pts in the community setting to reflect the routine care of B-CLL pts. Therefore, this observational study was designed to characterize the type, severity and frequency of all adverse events occurring on-treatment and in the year following rituximab infusion. A secondary objective was to assess response rate (CR/nPR/PR), duration of response, disease-free survival, overall survi…

Antioxidant enzyme activities and the production of MDA and 8-oxo-dG in chronic lymphocytic leukemia.

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…

Oxidative imbalance in low/intermediate-1-risk myelodysplastic syndrome patients: The influence of iron overload

Abstract Objective To assess the generation of reactive oxygen species (ROS) and the involvement of the main antioxidant pathways in low/intermediate-1-risk myelodysplastic syndromes (MDS) with iron overload (IOL). Methods We examined the levels of superoxide anion (O2 −), hydrogen peroxide (H2O2), antioxidants (glutathione, GSH; superoxide dismutase, SOD; catalase, CAT; and glutathione peroxidase, GPx), mitochondrial membrane potential (ΔΨm), and by-products of oxidative damage (8-isoprostanes and 8-oxo-7,8-dihydro-2′-deoxyguanosine, 8-oxo-dG) in 42 MDS patients (28 without IOL at diagnosis, and 14 who developed IOL) and 20 healthy subjects. Results Patients with IOL showed higher O2 − lev…

Chronic Lymphocytic Leukemia: Correlations Between Oxidative Stress Metabolism and Cytogenetic Subgroups

Abstract The chronic lymphocytic leukemia (B cell-CLL) is a heterogeneous lymphoproliferative disorder susceptible to oxidative stress. The excessive production of reactive oxygen intermediates above the capability of naturally produced antioxidants may result in the instability of essential macromolecules, and represents the molecular basis of many diseases including cancer. Highly reactive radicals interact with DNA inducing a multitude of oxidative modifications, and are implicated in mutagenesis due to misreplication of the damaged base 8-oxo-2′-deoxiguanosine (8-oxo-dG). Furthermore, protooncogene activation and/or tumor suppressor gene inhibition has been reported as a consequence of …

Clinical and Biological Characterization of Patients with Low/Intermediate-1 Risk Myelodysplastic Syndrome and Iron Overload

Abstract Abstract 4956 Introduction. Patients with Myelodysplastic Syndrome (MDS) are susceptible to developing iron overload as a response to the red blood cell (RBC) transfusions and ineffective hematopoiesis. This iron overload (IOL) is characterized by an increase in oxygen-reactive species accompanied by a decrease in antioxidants, and results in hepatic, cardiac and endocrine disorders, as well as an increased risk of infection. Ineffective hematopoiesis promotes iron absorption at intestinal level. This process is enhanced by the presence of mutations in the hereditary hemochromatosis gene (HFE). This study aims to define the features that accompany patients with iron overload, compa…

Early ROS-mediated DNA damage and oxidative stress biomarkers in Monoclonal B Lymphocytosis

Monoclonal B Lymphocytosis (MBL) is defined as asymptomatic monoclonal B-cell expansion characterised by a CLL-phenotype, but with less than 5 x 10(9)/I circulating cells. Reactive oxygen species (ROS)-mediated cell damage plays a critical role in the initiation of carcinogenesis as well as in malignant transformation. The goal of this study was to perform an analysis of the oxidative stress statuses of patients affected by MBL and chronic lymphocytic leukaemia (CLL). We examined peripheral blood and urine specimens from 29 patients with MBL, 55 with CLL and 31 healthy subjects. There was a significant increase in the occurrence of the mutagenic base 8-oxo-2'-deoxiguanosine (8-oxo-dG) in th…

Auto-immune haemolytic anaemia in ulcerative colitis: report of three cases.