RESUMEN
The levels of CD19 (+) and CD20(+) microvesicles were estimated in the blood of patients with B-cell chronic lymphocytic leukemia and indolent non-Hodgkin lymphoma by flow cytometry method. It was found that the number of B cell microvesicles is several times higher in patients than in volunteers. The level of CD20 (+) microvesicles directly correlated with the number of CD20(+) lymphocytes in patients with chronic lymphoproliferative diseases. Extramedullary tumors cells can be a source of CD19 (+) microvesicles.
Asunto(s)
Micropartículas Derivadas de Células/metabolismo , Leucemia Linfocítica Crónica de Células B/sangre , Linfoma no Hodgkin/sangre , Adulto , Anciano , Antígenos CD19/metabolismo , Antígenos CD20/metabolismo , Linfocitos B/inmunología , Linfocitos B/metabolismo , Estudios de Casos y Controles , Femenino , Humanos , Inmunofenotipificación , Leucemia Linfocítica Crónica de Células B/inmunología , Recuento de Linfocitos , Linfoma no Hodgkin/inmunología , Masculino , Persona de Mediana EdadRESUMEN
Enzymes of the cytochrome P450 and GSTP1 families play a pivotal role in the metabolism of a wide variety of antitumor drugs and polymorphisms of genes encoding for metabolizing enzymes can affect drug efficacy and toxicity. We studied the associations between functionally significant gene polymorphisms CYP2C8, CYP2C9, CYP2C19, CYP3A5, and GSTP1 and clinical response to chemotherapy in patients with chronic lymphoproliferative diseases. Significant correlations with chemotherapy resistance were observed for CYP2C8 3 (OR=7.05; CI 95%=1.76-29.55) and CYP2C9 2 polymorphisms (OR=4.1; CI 95%=1.03-16.81). No significant association between chemotherapy resistance and other examined polymorphisms were found.
Asunto(s)
Hidrocarburo de Aril Hidroxilasas/genética , Resistencia a Antineoplásicos/genética , Inactivación Metabólica/genética , Trastornos Linfoproliferativos/genética , Polimorfismo Genético , Alelos , Antineoplásicos/uso terapéutico , Enfermedad Crónica , Citocromo P-450 CYP2C8 , Citocromo P-450 CYP2C9 , Femenino , Frecuencia de los Genes , Genotipo , Heterocigoto , Homocigoto , Humanos , Trastornos Linfoproliferativos/tratamiento farmacológico , Trastornos Linfoproliferativos/enzimología , Trastornos Linfoproliferativos/patología , Masculino , Persona de Mediana EdadRESUMEN
Analysis of variants of exon 7 sequences in cytochrome P450 gene 3A4 in a sample of Caucasoid persons was carried out. The effect of these variants on activity of CYP3A was assessed by the level of cortisol 6beta-hydroxylation. Alleles CYP3A4*5 and *17 were not detected: probably, these mutations are rare and consequently they have little effect on the character of polymorphic distribution of CYP3A4 activity in this population. The incidence of CYP3A4*2 was 5.26%. The 6betaOH-cortisol/cortisol ratio in an individual with CYP3A4*2/*2 genotype was 7.408, which corresponded to "slow metabolizer" phenotype in this sample.
Asunto(s)
Sistema Enzimático del Citocromo P-450/genética , Exones/genética , Hidrocortisona/metabolismo , Mutación/genética , Citocromo P-450 CYP3A , Sistema Enzimático del Citocromo P-450/metabolismo , Cartilla de ADN , Finlandia , Frecuencia de los Genes , Humanos , Hidroxilación , Siberia , Población Blanca/genéticaRESUMEN
Study of MDR1 polymorphism in intron 6 and exon 12 of healthy individuals and patients with chronic lymphoproliferative diseases showed that the presence of mutant 6+139T allele is a factor determining resistance to lymphoproliferative diseases. Comparison of genotyping results in 53 patients and the data on the efficiency of drug therapy showed no significant associations of C(6+139)T and C(1236)T genotypes with drug resistance.
Asunto(s)
Resistencia a Antineoplásicos/genética , Genes MDR , Trastornos Linfoproliferativos/genética , Polimorfismo Genético , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Secuencia de Bases , Estudios de Casos y Controles , ADN/genética , Femenino , Humanos , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Leucemia Linfocítica Crónica de Células B/genética , Linfoma no Hodgkin/tratamiento farmacológico , Linfoma no Hodgkin/genética , Trastornos Linfoproliferativos/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Mutación , Federación de RusiaRESUMEN
Study of polymorphism in MDR1 gene exons 21 and 26 revealed that T2677T and T3435T alleles are not a factor predisposing to lymphoproliferative diseases, but they determine the efficiency chemotherapy. Individuals with T2677T and T3435T haplotypes are at highest risk of drug resistance. Association between genotypes G2677T and C3435T was detected in normal subjects and in patients with lymphoproliferative diseases.