Search results for "azacitidine"
showing 10 items of 38 documents
Validation of response assessment according to international consortium for MDS/MPN criteria in chronic myelomonocytic leukemia treated with hypometh…
2017
Validation of response assessment according to international consortium for MDS/MPN criteria in chronic myelomonocytic leukemia treated with hypomethylating agents
Molecular predictors of response to decitabine in advanced chronic myelomonocytic leukemia: a phase 2 trial.
2011
Abstract Hydroxyurea is the standard therapy of chronic myelomonocytic leukemia (CMML) presenting with advanced myeloproliferative and/or myelodysplastic features. Response to hypomethylating agents has been reported in heterogeneous series of CMML. We conducted a phase 2 trial of decitabine (DAC) in 39 patients with advanced CMML defined according to a previous trial. Median number of DAC cycles was 10 (range, 1-24). Overall response rate was 38% with 4 complete responses (10%), 8 marrow responses (21%), and 3 stable diseases with hematologic improvement (8%). Eighteen patients (46%) demonstrated stable disease without hematologic improvement, and 6 (15%) progressed to acute leukemia. With…
Impact of Clinical Features, Cytogenetics, Genetic Mutations and Methylation of CDKN2B and DLC-1 Promoters on Treatment Response to Azacitidine
2019
Introduction : Azacitidine (AZA) is a DNA hypomethylating agent used in myeloid neoplasms, however approximately half of patients show treatment failure or relapse. Last years, several studies have showed that genetic mutations may influence on response and survival of the treated patients. Other biomarkers that have traditionally been associated with the response to AZA are the recovery of the platelet count and the presence of abnormalities in the chromosome 7. Finally, the methylation dynamics of genes promoters could be a useful tool to predict the clinical response. Aim: To assess the predictive value on response to AZA of clinical features, cytogenetics, genetic mutations and the meth…
Role and importance of polymorphisms with respect to DNA methylation for the expression of CYP2E1 enzyme
2014
Different individuals possess slightly different genetic information and show genetically-determined differences in several enzyme activities due to genetic variability. Following an integrated approach, we studied the polymorphisms and methylation of sites contained in the 5' flanking region of the metabolizing enzyme CYP2E1 in correlation to its expression in both tumor and non-neoplastic liver cell lines, since to date little is known about the influence of these (epi)genetic elements in basal conditions and under induction by the specific inductor and a demethylating agent. In treated cells, reduced DNA methylation, assessed both at genomic and gene level, was not consistently associate…
Outcome of lower-risk patients with myelodysplastic syndromes without 5q deletion after failure of erythropoiesis-stimulating agents
2017
Purpose Most anemic patients with non-deleted 5q lower-risk myelodysplastic syndromes (MDS) are treated with erythropoiesis-stimulating agents (ESAs), with a response rate of approximately 50%. Second-line treatments, including hypomethylating agents (HMAs), lenalidomide (LEN), and investigational drugs, may be used after ESA failure in some countries, but their effect on disease progression and overall survival (OS) is unknown. Here, we analyzed outcome after ESA failure and the effect of second-line treatments. Patients and Methods We examined an international retrospective cohort of 1,698 patients with non-del(5q) lower-risk MDS treated with ESAs. Results Erythroid response to ESAs was 6…
Infectious complications in patients with myelodysplastic syndromes: A review of the literature with emphasis on patients treated with 5-azacitidine.
2017
Myelodysplastic Syndromes are oligo-clonal stem cell disorders that are associated with cytopenias in the peripheral blood. Major causes for morbidity and mortality in myelodysplastic syndromes (MDS) patients are infections mostly due to bacteria or fungi. Beside leucopenia per se in affected patients, function of white blood cells particularly that of neutrophils seems to be impaired. Here we summarize the available data on infections in MDS patients in general and particularly those treated with 5-azacitidine.
Validation of the High-Risk Prognostic Score Defined By the Presence of Mutations in NRAS or TP53 in a Cohort of 497 Patients with Acute Myeloid Leuk…
2020
INTRODUCTION Older AML patients have a different mutational landscape compared to younger patients. The prognostic classification of AML proposed by the European Leukemia Net (2017) is based on the presence of mutations in FLT3 (ITD), NPM1, CEBPA, RUNX1, ASXL1 and TP53. However, our group has identified a high-risk prognostic score in older patients with AML, who are undergoing treatment with azacitidine or low-dose cytarabine plus fludarabine, which predict a shorter survival. OBJECTIVE Validation of the previously identified high-risk prognostic score, defined by the presence of mutations in NRAS or TP53, in 3 cohorts of patients with AML who have been studied by NGS with a custom panel i…
Genome-wide promoter methylation analysis in neuroblastoma identifies prognostic methylation biomarkers.
2012
Background: Accurate outcome prediction in neuroblastoma, which is necessary to enable the optimal choice of risk-related therapy, remains a challenge. To improve neuroblastoma patient stratification, this study aimed to identify prognostic tumor DNA methylation biomarkers.Results: To identify genes silenced by promoter methylation, we first applied two independent genome-wide methylation screening methodologies to eight neuroblastoma cell lines. Specifically, we used re-expression profiling upon 5-aza-2'-deoxycytidine (DAC) treatment and massively parallel sequencing after capturing with a methyl-CpG-binding domain (MBD-seq). Putative methylation markers were selected from DAC-upregulated …
5-Azacytidine Inhibits the Activation of Senescence Program and Promotes Cytotoxic Autophagy during Trdmt1-Mediated Oxidative Stress Response in Insu…
2022
5-Azacytidine (5-azaC), a methyltransferase inhibitor and anticancer drug, can promote several cellular stress responses such as apoptosis, autophagy, and senescence. The action of 5-azaC is complex and can be modulated by dose, time of treatment, and co-administration with oxidants. Insulinoma is a rare pancreatic neuroendocrine tumor with limited chemotherapeutic options. In the present study, two cellular models of insulinoma were considered, namely NIT-1 and β-TC-6 mouse cells, to evaluate the effects of 5-azaC post-treatment during hydrogen peroxide-induced oxidative stress. 5-azaC attenuated the development of oxidant-induced senescent phenotype in both cell lines. No pro-apoptotic ac…
Both mature KIR+ and immature KIR- NK cells control pediatric acute B-cell precursor leukemia in NOD.Cg-Prkdcscid IL2rgtmWjl/Sz mice.
2014
Therapeutic natural killer (NK)-cell-mediated alloreactivity toward acute myeloid leukemia has largely been attributed to mismatches between killer immunoglobulin-like receptors (KIRs) on NK cells and their ligands, HLA class I molecules, on target cells. While adult acute B-cell precursor leukemia (BCP-ALL) appears to be resistant to NK-cell-mediated lysis, recent data indicate that pediatric BCP-ALL might yet be a target of NK cells. In this study, we demonstrate in a donor-patient-specific NOD.Cg-Prkdc(scid) IL2rg(tmWjl)/Sz (NSG) xenotransplantation model that NK cells mediate considerable alloreactivity toward pediatric BCP-ALL in vivo. Notably, both adoptively transferred mature KIR(+)…