Exploring the significance of MDM2 gene promoter variants in chronic myeloid leukemia.

Tyrosine kinase inhibitors (TKIs) targeting BCR::ABL1 are highly successful in chronic myeloid leukemia (CML). However, extensive interpatient variability in therapeutic responses and resistance supports the need to find new prognostic biomarkers. We have previously reported that TP53 SNP215 variant affects CML risk and clinical outcome.

Genetic variability profiling of the p53 signaling pathway in chronic lymphocytic leukemia. Individual and combined analysis of TP53, MDM2 and NQO1 gene variants.

TP53 gene disruption, including 17p13 deletion [del(17p)] and/or TP53 mutations, is a negative prognostic biomarker in chronic lymphocytic leukemia (CLL) associated with disease progression, treatment failure and shorter survival. Germline variants in p53 signaling pathway genes could also lead to p53 dysfunction, but their involvement in CLL has not been thoroughly evaluated. The aim of this study was to determine the association of TP53, MDM2 and NQO1 gene variability with clinical and genetic data of CLL patients.

Discrimination of the chemotherapy resistance status of human leukemia and glioblastoma cell lines by MALDI-TOF-MS profiling.

Chemotherapy mistreatment is partially due to a lack of rapid and reliable tools to discriminate between sensitive and resistant phenotypes. In many cases, the resistance mechanism is not fully understood, contributing to the diagnostic tools' absence. This work aims to determine the capacity of MALDI-TOF-MS profiling to discriminate between chemotherapy-resistant and sensitive phenotypes in leukemia and glioblastoma cells.

Single nucleotide polymorphism in PTEN-Long gene: A risk factor in chronic myeloid leukemia.

The BCR-ABL1 oncogene is associated with chronic myeloid leukemia (CML) pathogenesis, but the molecular mechanisms that initiate leukemogenesis are still unclear. Cancer pathogenesis has been associated with genetic alterations that may lead to inactivation of tumor suppressor genes. Phosphatase and tensin homolog (PTEN) is frequently deleted or inactivated in various tumors.

Gene polymorphism profiles of drug-metabolising enzymes GSTM1, GSTT1 and GSTP1 in an Argentinian population.

Background: Glutathione S-transferases (GSTs) are drug-metabolising enzymes involved in biotransformation of carcinogens, drugs, xenobiotics and oxygen free radicals. Polymorphisms of GST genes contribute to inter-individual and population variability in the susceptibility to environmental risk factors, cancer predisposition and pharmacotherapy responses. However, data about GST variability in Argentina are lacking.

GSTM1 and GSTP1, but not GSTT1 genetic polymorphisms are associated with chronic myeloid leukemia risk and treatment response.

Background: Chronic myeloid leukemia (CML) is associated to the BCR-ABL1 oncogene and can successfully be treated with tyrosine kinase inhibitors (TKIs). However, it remains still under investigation which molecular factors may influence CML risk or varying responses to TKIs. The aim of this study was to assess the role of Glutathione-S-transferases (GSTs) genetic polymorphisms in CML susceptibility and TKI clinical outcome.

TP53 codon 72 polymorphism predicts chronic myeloid leukemia susceptibility and treatment outcome.

BCR-ABL1 gene is a key molecular marker of chronic myeloid leukemia (CML), but it is still unclear which molecular factors may influence CML risk or lead to variable responses to tyrosine kinase inhibitors (TKIs). The aim of this study was to investigate the impact of TP53 c.213 G>C(Arg72Pro; rs1042522) polymorphism on CML risk and its correlation with clinical outcome.

Polymorphic variants of GSTM1, GSTT1, and GSTP1 genes in childhood acute leukemias: A preliminary study in Argentina.

Background And Aim: Despite recent major advances in leukemia research, the etiopathogenesis of childhood leukemias remains far elusive. Individual predisposing factors, including polymorphisms in detoxification enzymes, have been implicated in the molecular pathogenesis and heterogeneity of the disease. Genetic polymorphisms of glutathione S-transferases (GSTs) that alter enzyme activity could be an additional factor that increases the risk of acute leukemia, but data are lacking in Argentina.

Glutathione S-transferase gene polymorphisms in celiac disease and their correlation with genomic instability phenotype.

Background And Objective: Genomic instability and reduced glutathione S-transferase (GST) activity have been identified as potential risk factors for malignant complications in celiac disease (CD). In this study, we assessed the possible influence of GST polymorphisms on genome instability phenotypes in a genetically characterised group of celiac patients from previous studies.

Methods: The deletion polymorphisms in GSTM1 and GSTT1 genes and the single-nucleotide polymorphism GSTP1 c.

Glutathione S-transferase P1 mRNA expression in plasma cell disorders and its correlation with polymorphic variants and clinical outcome.

Background: Glutathione S-transferase P1 (GSTP1) is an important phase II enzyme involved in detoxification of carcinogens. GSTP1 gene overexpression has been observed in a variety of human cancers but there are no studies in plasma cell disorders. The aim of this study was to examine GSTP1 mRNA expression level in multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS).

[Genetic alterations, genomic instability and cancer in celiac disease].

Celiac disease (CD) is a common autoimmune disorder characterized by intestinal inflammation and mucosal atrophy triggered by dietary gluten in genetically predisposed individuals. Although, most patients improve with a gluten-free diet, a small percentage (2-5%) develops refractoriness or pre- and malignant complications. Malignancies are the most serious complications of CD, including gastrointestinal carcinomas and non-Hodgkin lymphoma, particularly Enteropathy-type T-cell lymphoma, a rare high-grade T-cell non-Hodgkin lymphoma of the small intestine, almost exclusively observed in CD patients.

Analysis of genomic instability in adult-onset celiac disease patients by microsatellite instability and loss of heterozygosis.

Background And Aims: Malignant complications of celiac disease (CD) include carcinomas and lymphomas. The genetic basis behind cancer development in CD is not known, but acquisition of genetic abnormalities and genomic instability has been involved. The aim of this study was to explore molecular characteristics of genomic instability in CD patients by analyzing microsatellite instability (MSI) and loss of heterozygosis (LOH) with carefully selected microsatellites.

Feasibility of a cost-effective approach to evaluate short tandem repeat markers suitable for chimerism follow-up.

Background: Precise chimerism monitoring is important for the prediction of the success of allogeneic bone marrow transplantation (BMT). Most of the current procedures employed for chimerism follow-up with short tandem repeat (STR) markers are either time-consuming, labor-intensive, or use expensive assays, making it burdensome to perform large-scale studies of transplanted patients.

Aim: To set-up a simple nonradioactive method to investigate a set of STR markers that could be used in the evaluation of chimerism status after allogeneic BMT.

Expression of common fragile sites in two Ceboidea species: Saimiri boliviensis and Alouatta caraya (Primates: Platyrrhini).

Fragile sites are points of preferential breakage that may be involved in chromosome rearrangements. Induction of common fragile sites (c-fra) and spontaneous breakage were analyzed in two New World Monkeys species: Saimiri boliviensis (SBO) and Alouatta caraya (ACA). Spontaneous chromosome aberrations were analyzed on untreated lymphocyte cultures with Brögger's formula (1977).

Correlation between chromosome damage and apoptosis induced by fludarabine and idarubicin in normal human lymphocytes.

Fludarabine (FLU, a fluorinated purine analog) and idarubicin (IDA, a DNA-topoisomerase II poison) are frequently used in cancer chemotherapy. The effects of these drugs on cultured normal human lymphocytes were studied to establish the possible involvement of chromosome damage in the apoptotic program. Chromosome aberrations (CA) were evaluated in first division metaphases and the apoptotic process was measured by morphological and electrophoretical techniques.

Evidence of chromosome instability in chronic pancreatitis.

In the current study we analyzed chromosome instability on peripheral blood lymphocytes cultured from 7 untreated patients with chronic pancreatitis (CP) by assessing telomeric associations (TAS), chromosome aberrations (CA) and sister chromatid exchanges (SCE). Seven healthy individuals were also analyzed. Mean frequencies of TAS were significantly higher in CP patients (X +/- SE: 11.

High frequencies of telomeric associations, chromosome aberrations, and sister chromatid exchanges in ulcerative colitis.

Objective: Chromosome instability provides a predisposing background to malignancy, contributing to the crucial genetic changes in multistep carcinogenesis. The aim of this work was to analyze chromosome instability in patients with ulcerative colitis (UC) to achieve a better understanding of the increased risk for colorectal cancer.

Methods: Peripheral blood lymphocyte cultures from 20 untreated UC patients and 24 controls were used to study chromosome instability by assessing telomeric associations (TAS), chromosome aberrations (CA), and sister chromatid exchanges (SCE).

Spontaneous breakage and fragile site expression in chronic lymphocytic leukemia.

It has been suggested that genetic predisposition to cancer might be related to spontaneous chromosome instability or to fragile site expression. Therefore, spontaneous breakage and fragile sites were analyzed in nine untreated chronic lymphocytic leukemia (CLL) patients to determine their relation to cancer rearrangements. Five cases presented spontaneous gaps and breaks with a random distribution of breakpoints.

Chromosome instability in untreated adult celiac disease patients.

Spontaneous chromosome aberrations (CAs) and induced fragile sites (FSs) were analysed in 12 untreated adult coeliac disease (CD) patients and 8 healthy controls. Blood lymphocytes from each individual were cultured for 72 h at 37 degrees C in F-10 medium with 5% fetal calf serum and 0.1 ml phytohemagglutinine.

[Participation of fragile sites in cancer].

Structural and numerical chromosomal abnormalities are frequent findings in neoplastic cells. The origin of structural rearrangements is probably due to the existence of specific labile areas on human chromosomes. These areas, named fragile sites (FS), are prone to chromosomal breakage and rearrangements, playing an important role in the first steps of carcinogenesis.

Non-random distribution of spontaneous chromosome aberrations in two Bloom Syndrome patients.

The distribution of breakpoints involved in spontaneous chromosome aberrations (CA) was analyzed in lymphocytes from a family with Bloom's Syndrome (BS) and 9 healthy individuals. Standard and G-banded metaphases from each individual were analyzed to allow the identification of the breakpoints involved in spontaneously occurring chromosome aberrations. A total of 85 breakpoints in BS patients, 17 in their parents and 35 in controls, could be exactly localized to specific chromosome bands.

Chromosome instability in lymphocytes from patients with celiac disease.

Cytogenetic studies were performed in celiac disease (CD) patients to determine if the presence of chromosome instability is related to the predisposition to cancer. Chromosome aberrations (CA) and sister chromatid exchange (SCE) frequencies in peripheral blood lymphocyte cultures from untreated CD patients and healthy controls were analyzed. Patients showed aberrations in 23% of cells, while only 3% were detected in the control group (p < 0.

Spontaneous chromosome aberrations in Fanconi's anemia patients are located at fragile sites and acute myeloid leukemia breakpoints.

Spontaneous chromosome aberrations (CA) were analyzed in 3 Fanconi's anemia (FA) patients, 8 family members, and 9 healthy individuals. Peripheral blood lymphocytes obtained from each individual were cultured and cytogenetic analysis was performed on standard and sequential G-banded metaphases. The numbers of abnormal cells and breaks were found to be higher in AF patients compared to the other groups (p < 0.