0000000000246599
AUTHOR
Blanca Navarro
Impact of Clinical Features, Cytogenetics, Genetic Mutations and Methylation of CDKN2B and DLC-1 Promoters on Treatment Response to Azacitidine
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…
Clinical evaluation of the European LeukaemiaNet criteria for clinicohaematological response and resistance/intolerance to hydroxycarbamide in essential thrombocythaemia
Standardized criteria of response to treatment and a unified definition of resistance/intolerance to hydroxycarbamide (HC) in essential thrombocythaemia (ET) have been proposed by the European LeukaemiaNet (ELN). We have retrospectively evaluated such criteria in 166 ET patients treated with HC for a median of 4·5 years. Overall, 134 patients achieved a complete clinicohaematological response (CR) and 25 a partial response. Thirty-three patients met at least one of the ELN criteria defining resistance (n = 15) or intolerance (n = 21) to HC. Fifteen cases developed anaemia with thrombocytosis, which was associated with a high incidence of myelofibrosis and death from any cause. Other definit…
Synergistic Antioncogenic Activity of Azacitidine and Curcumin in Myeloid Leukemia Cell Lines and Patient Samples.
Background/aim Azacitidine (AZA) is a hypomethylating agent used in myeloid neoplasms, however, approximately half of patients show treatment failure or relapse. This in vitro study investigated the effect of the combination of AZA with the natural compound curcumin (CUR) in increasing its efficacy. Materials and methods We analyzed the effects of AZA plus CUR on proliferation, apoptosis, cell cycle and differentiation in myeloid leukemic cell lines (U-937, HL-60, K-562, and OCI-AML3) and bone marrow samples of patients. Results The results showed a synergy between AZA and CUR in all leukemic lines and in most leukemic samples, with a decrease in proliferation and an increase in apoptosis c…
Bone marrowVEGFCexpression is associated with multilineage dysplasia and several prognostic markers in adult acute myeloid leukemia, but not with survival
Vascular endothelial growth factor C (VEGFC) stimulates leukemia cell proliferation and survival, and promotes angiogenesis. We studied VEGFC expression in bone marrow samples from 353 adult acute myeloid leukemia (AML) patients and its relationship with several clinical, cytogenetic, and molecular variables. We also studied the expression of 84 genes involved in VEGF signaling in 24 patients. We found that VEGFC expression was higher in AML patients with myelodysplasia-related changes (AML-MRC) than in patients with non-AML-MRC. We also found an association between VEGFC expression and the patient cytogenetic risk group, with those with a worse prognosis having higher VEGFC expression leve…
Use of rivaroxaban for the prevention of stroke in patients with nonvalvular atrial fibrillation in Spain
Aim: To analyze the clinical profile and rates of stroke, major bleeding and intracranial hemorrhage of patients with atrial fibrillation (AF) treated with rivaroxaban in clinical practice. Methods: Retrospective study of AF patients anticoagulated with rivaroxaban in a Healthcare Area of Valencia, Spain. Patients started treatment with rivaroxaban from July 2012 to December 2015. Results: A total of 230 patients (mean age 76.9 ± 9.9 years; CHA2DS2-VASc 4.3 ± 1.7; HAS-BLED 1.7 ± 0.9) were included. Rates of stroke, major bleeding and intracranial bleeding were 0.4, 1.9 and 0.5 events per 100 patient-years, respectively. Conclusion: In this cohort of AF patients anticoagulated with rivaroxa…
Does Empagliflozin Modulate Leukocyte–Endothelium Interactions, Oxidative Stress, and Inflammation in Type 2 Diabetes?
Sodium-glucose co-transporter 2 inhibitors (iSGLT2) have been linked to cardiovascular risk reduction in patients with type 2 diabetes (T2D). However, their underlying molecular mechanisms remain unclear. This study aimed to evaluate the effects of empagliflozin, a novel potent and selective iSGLT-2, on anthropometric and endocrine parameters, leukocyte–endothelium interactions, adhesion molecules, ROS production, and NFkB-p65 transcription factor expression. According to standard clinical protocols, sixteen T2D patients receiving 10 mg/day of empagliflozin were followed-up for 24 weeks. Anthropometric and analytical measurements were performed at baseline, 12 weeks, and 24 weeks. Interacti…
Ighv Mutational Status By Deep Next Generation Sequencing Refines Ighv Sanger Sequencing Classification in Patients with Chronic Lymphocytic Leukaemia
Introduction: Determination of the mutational status of rearranged immunoglobulin heavy chain variable (IgHV) genes in patients with Chronic Lymphocytic Leukaemia (CLL), is considered one of the most important prognostic factors: patients with unmutated IgHV (UM; ≥98% of identity to the germline) genes have a more aggressive disease course and develop more frequently unfavourable genetic deletions or mutations than patients with mutated IgHV (M; ≤98%). Mutational status, is currently determined by Sanger sequencing (Sseq) that allows the analysis of the major clone, however, international guidelines recommend caution in assigning mutational status in cases with "Borderline" IgHV identity (9…
Efecto del telmisartán en el estrés oxidativo y actividad antioxidante en leucocitos de sangre periférica de pacientes hipertensos
Resumen Introduccion Se han determinado el estres oxidativo y la actividad enzimatica antioxidante en leucocitos de pacientes hipertensos inmediatamente antes de iniciar el tratamiento con 80 mg/dia de telmisartan y despues de 2 meses de instaurada la medicacion. Adicionalmente se ha valorado en paralelo un grupo control. Material y metodos Como marcador de estres oxidativo, se ha determinado el potencial de membrana mitocondrial (ψΔ) en leucocitos. La actividad antioxidante se ha determinado midiendo la actividad superoxido dismutasa y catalasa en lisados leucocitarios. Resultados Nuestros resultados muestran mayor estres oxidativo y mayor actividad antioxidante en los pacientes en situaci…
Easy One-Step Amplification and Labeling Procedure for Copy Number Variation Detection.
Abstract Background The specific characteristics of copy number variations (CNVs) require specific methods of detection and characterization. We developed the Easy One-Step Amplification and Labeling procedure for CNV detection (EOSAL-CNV), a new method based on proportional amplification and labeling of amplicons in 1 PCR. Methods We used tailed primers for specific amplification and a pair of labeling probes (only 1 labeled) for amplification and labeling of all amplicons in just 1 reaction. Products were loaded directly onto a capillary DNA sequencer for fragment sizing and quantification. Data obtained could be analyzed by Microsoft Excel spreadsheet or EOSAL-CNV analysis software. We d…
Detection of Immunoglobulin Heavy Chain Gene Clonality By High-Throughput Sequencing for Minimal Residual Disease Monitoring in Chronic Lymphocytic Leukaemia
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 …
Therapy-related acute myeloid leukemia developing 14 years after allogeneic hematopoietic stem cell transplantation, from a persistent R882H- DNMT3A mutated clone of patient origin
Abstract Background Therapy-related acute myeloid leukemia (t-AML) develops in patients with prior exposure to cytotoxic therapies. Selection of a pre-existing TP53 mutated clone prone to acquire additional mutational events has been suggested as the main pathogenic mechanism of t-AML. Here, we report a unique case of t-AML which developed from a pre-existing DNMT3A mutated clone that persisted in the patient for more than 10 years despite treatment with intensive chemotherapy and allogeneic hematopoietic stem cell transplantation (alloHSCT). Case presentation A 42-year-old male was diagnosed with AML harboring a normal karyotype and mutations in the NPM1 (c.863_864ins, p.W288 fs*12), DNMT3…
Cytomegalovirus DNAemia in patients with de novo acute myeloid leukemia undergoing cytotoxic chemotherapy
There is evidence suggesting that cytomegalovirus (CMV) reactivation following allogeneic hematopoietic stem cell transplantation (allo-HSCT) may be associated with a lower relapse incidence in acu...