RESUMO
We report four cases of non-Hodgkin lymphoma involving the nasopharynx. Clinical, radiological, histological and treatment modalities are described. The four patients were male and aged 20, 42, 71 and 77 years. The symptoms were nasal obstruction with epistaxis in three cases and a cervical node in the fourth case. The histological type was a non-Hodgkin lymphoma of phenotype B with large cells CD20+ in the four cases. The treatment consisted in radiotherapy and chemotherapy.
Assuntos
Linfoma Difuso de Grandes Células B , Neoplasias Nasofaríngeas , Adulto , Idoso , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/radioterapia , Masculino , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/radioterapia , Adulto JovemRESUMO
Combined deficiency of coagulation factor V (FV) and factor VIII (FVIII) (F5F8D) is a rare autosomal recessive disorder characterized by mild-to-moderate bleeding and reduction in FV and FVIII levels in plasma. F5F8D is caused by mutations in one of two different genes, LMAN1 and MCFD2, which encode proteins that form a complex involved in the transport of FV and FVIII from the endoplasmic reticulum to the Golgi apparatus. Here, we report the identification of a novel mutation Asp89Asn in the MCFD2 gene in a Tunisian patient. In the encoded protein, this mutation causes substitution of a negatively charged aspartate, involved in several structurally important interactions, to an uncharged asparagine. To elucidate the structural effect of this mutation, we performed circular dichroism (CD) analysis of secondary structure and stability. In addition, CD analysis was performed on two missense mutations found in previously reported F5F8D patients. Our results show that all analysed mutant variants give rise to destabilized proteins and highlight the importance of a structurally intact and functional MCFD2 for the efficient secretion of coagulation factors V and VIII.
Assuntos
Deficiência do Fator V/genética , Hemofilia A/genética , Mutação/genética , Proteínas de Transporte Vesicular/genética , População Negra , Dicroísmo Circular , Análise Mutacional de DNA , Éxons/genética , Feminino , Predisposição Genética para Doença/genética , Humanos , Tunísia , Proteínas de Transporte Vesicular/química , Adulto JovemRESUMO
BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) exhibits heterogeneous clinical features and a marked variable response to treatment. PATIENTS AND METHODS: We investigated the prognostic significance of the methylation status of DAPK, GSTP1, P14, P15, P16, P33, RB1, SHP1, CDH1, APC, BLU, VHL, TIMP3, and RASSF1A genes in 46 DLBCL specimens from Tunisian patients. Methylation status of each gene was correlated with clinicopathological parameters including the International Prognostic Index (IPI), the germinal center immunophenotype, and response to treatment and survival. Overall survival (OS) and disease-free survival (DFS) rates were calculated by the Kaplan-Meier method and differences were compared with the log-rank test. RESULTS: Hypermethylation of SHP1 was associated with elevated lactate dehydrogenase level (P = 0.031). P16 and VHL were frequently hypermethylated in patients with high IPI scores (P = 0.006 and 0.004) and a performance status of two or more (P = 0.007 and 0.047). In addition, hypermethylation of P16 was significantly associated with advanced clinical stages and B symptoms (P = 0.041 and 0.012). Interestingly, hypermethylation of DAPK was significantly correlated with resistance to treatment (P = 0.023). With regard to survival rates, promoter hypermethylation of DAPK, P16, and VHL were significantly associated with shortened OS (P = 0.003, 0.001, and 0.017, respectively) and DFS (P = 0.006, 0.003, and 0.046, respectively). In multivariate analysis, hypermethylation of DAPK remains an independent prognostic factor in predicting shortened OS (P = 0.001) and DFS (P = 0.024), as well as the IPI and the germinal center status. CONCLUSIONS: This study demonstrates that DLBCLs with hypermethylated P16, VHL, DAPK, and SHP1 commonly show a biologically aggressive phenotype and worse prognosis. Interestingly, hypermethylation of DAPK was found to be an independent prognostic factor that may be used in conjunction with the conventional prognostic factors such as the IPI and the germinal center status.
Assuntos
Ilhas de CpG , Metilação de DNA , Linfoma Difuso de Grandes Células B/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , DNA de Neoplasias/genética , Intervalo Livre de Doença , Feminino , Humanos , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Regiões Promotoras GenéticasRESUMO
The molecular analysis of chromosomal abnormalities associated with hematological malignancies allowed the identification of genes involved in theses rearrangements as well as of some recurrent mechanisms. Polymerase chain reaction (PCR) tools are now available to detect these rearrangements, allowing a better follow-up of these diseases. Chronic myeloid leukemia is a myeloproliferative disorder characterized by a reciprocal translocation t(9;22)(q34;q11) which results in a bcr-abl fusion gene. Retro-transcription polymerase chain reaction (RT-PCR) is used to detect bcr-abl to establish diagnosis and to monitor patients. We report here the results of 30 patients samples tested in the hematology laboratory at Pasteur Institute, diagnosed as chronic myeloid leukemia and monitored with RT-PCR. Our results highlight the interest of molecular tools to diagnose and monitor patients mainly when cytogenetic techniques are irrelevant such as cases with complex chromosomal rearrangements or when patients achieve Philadelphia negativity after treatment.
