RESUMEN
Classical myeloproliferative diseases can be divided into Philadelphia chromosome-positive chronic myeloid leukemia and Philadelphia chromosome-negative myeloproliferative neoplasm. The driver mutations of the latter occur in the Janus kinase 2 or calreticulin genes. The coincidence of Philadelphia chromosome-negative and -positive myeloproliferative neoplasms in the same patient is exceptionally rare in the literature. During the long-term follow-up of our 120 patients with chronic myeloid leukemia, we investigated the clinical data of patients in whom Philadelphia chromosome-negative myeloproliferative disease was also confirmed. Philadelphia chromosome was detected by classical cytogenetic methods and/or fluorescence in situ hybridization. The amount of BCR-ABLI fusion RNA was monitored by quantitative real-time polymerase chain reaction. Mutations in the Janus kinase 2 and calreticulin genes were detected by quantitative allele-specific polymerase chain reaction and fragment analysis. The dynamics of disease development were inferred from the change in the amount of mutant clones over time and from the clinical data. We identified four cases carrying both Philadelphia chromosome and Janus kinase 2/calreticulin gene mutation. In some cases, competition between the clones, in other cases their co-occurrence in a common clone was observed. Isolated thrombocytosis at the time of diagnosis or persisting thrombocytosis during targeted therapy with good molecular response may call attention to the possibility of the co-occurrence of the two diseases. Co-occurrence of Philadelphia chromosome-positive and -negative myeloproliferative neoplasms is more frequent than the literature suggests. If the disease has an unusual appearance, the association of the two myeloproliferative dieseases may be suspected.
Asunto(s)
Leucemia Mielógena Crónica BCR-ABL Positiva , Trastornos Mieloproliferativos , Trombocitosis , Calreticulina/genética , Calreticulina/uso terapéutico , Humanos , Hibridación Fluorescente in Situ , Janus Quinasa 2/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Mutación , Trastornos Mieloproliferativos/diagnóstico , Trastornos Mieloproliferativos/genética , Cromosoma FiladelfiaRESUMEN
Listeria monocytogenes NCTC10527 was examined with respect to its nonthermal inactivation kinetics in fermented sausages from four European countries: Serbia-Montenegro, Hungary, Croatia, and Bosnia-Herzegovina. The goal was to quantify the effect of fermentation and ripening conditions on L. monocytogenes with the simultaneous presence or absence of bacteriocin-producing lactic acid bacteria (i.e., Lactobacillus sakei). Different models were used to fit the experimental data and to calculate the kinetic parameters. The best model was chosen based on statistical comparisons. The Baranyi model was selected because it fitted the data better in most (73%) of the cases. The results from the challenge experiments and the subsequent statistical analysis indicated that relative to the control condition the addition of L. sakei strains reduced the time required for a 4-log reduction of L. monocytogenes (t(4D)). In contrast, the addition of the bacteriocins mesenterocin Y and sakacin P decreased the t(4D) values for only the Serbian product. A case study for risk assessment also was conducted. The data of initial population and t(4D) collected from all countries were described by a single distribution function. Storage temperature, packaging method, pH, and water activity of the final products were used to calculate the inactivation of L. monocytogenes that might occur during storage of the final product (U.S. Department of Agriculture Pathogen Modeling Program version 7.0). Simulation results indicated that the addition of L. sakei strains significantly decreased the simulated L. monocytogenes concentration of ready-to-eat fermented sausages at the time of consumption.
Asunto(s)
Conservación de Alimentos/métodos , Lactobacillus/fisiología , Listeria monocytogenes/crecimiento & desarrollo , Productos de la Carne/microbiología , Modelos Biológicos , Medición de Riesgo , Animales , Antibiosis , Bosnia y Herzegovina , Seguridad de Productos para el Consumidor , Croacia , Fermentación , Manipulación de Alimentos/métodos , Microbiología de Alimentos , Humanos , Hungría , Cinética , Listeria monocytogenes/aislamiento & purificación , Porcinos , YugoslaviaRESUMEN
Mutations of isocitrate dehydrogenase 1 and 2 (IDH1/2) are genetic alterations in acute myeloid leukemia (AML). The aim of our study was to investigate the frequency and prognostic effect of IDH1/2 mutations together followed by an individual analysis of each substitution in a Hungarian cohort consisting of 376 patients with AML. IDH1(mut) and IDH2(mut) were mutually exclusive, detected in 8.5% and 7.5% of cases, respectively. IDH1/2(mut) was associated with: older age (p = 0.001), higher average platelet count (p = 0.001), intermediate karyotype (p < 0.0001), NPM1(mut) (p = 0.022) and lower mRNA expression level of ABCG2 gene (p = 0.006). Overall survival (OS), remission and relapse rates were not different in IDH1(mut) or IDH2(mut) vs. IDH(neg). IDH1(mut) and IDH2(mut) were associated differently with NPM1(mut); co-occurrence was observed in 14.3% of IDH1 R132C vs. 70% of R132H carriers (p = 0.02) and in 47.4% of IDH2 R140Q vs. 0% of R172K carriers (p = 0.02). IDH1 R132H negatively influenced OS compared to IDH(neg) (p = 0.02) or R132C (p = 0.019). Particular amino acid changes affecting the same IDH1 codon influence the clinical characteristics and treatment outcome in AML.