RESUMEN
BACKGROUND: Activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) is characterized by chronic active B-cell receptor signaling and a constitutive activation of the NF-KB pathway. MYD88 L265P mutation occurs as a driving force of NF-KB overactivity in ABC-DLBCL. Nonetheless, in cases of DLBCL, the MYD88 L265P mutation has not yet been investigated in association with the tumour necrosis factor alpha induced protein3 (TNFAIP3) mutation. OBJECTIVE: To investigate the frequency of MYD88 and TNFAIP3 mutations in DLBCL and their association to the clinico-hematological profile. MATERIAL AND METHODS: We used real-time polymerase chain reaction in order to search for MYD88 L265P and TNFAIP3 mutations in 100 DLBCL patients. RESULTS: MYD88 L265P In 20% of cases, the CT heterozygous genotype was discovered. CT heterozygous genotype was more common in ABC type, stage IV, greater IPI groups, extra-nodal infiltration, and BM infiltration. It was also linked to a shorter OS. TNFAIP3 mutation GA heterozygous genotype was detected in 18% of the patients, with ABC-DLBCL subtype accounting for 77.8%. The GA heterozygous genotype was usually related with stage IV, extranodal infiltration, and a reduced life expectancy. CONCLUSION: MYD88 L265P and to lesser extent TNFAIP3 mutations are major mutations in ABC- DLBCL and may be predictive factors for poor OS in ABC- DLBCL patients.
Asunto(s)
Linfoma de Células B Grandes Difuso , Factor 88 de Diferenciación Mieloide , Proteína 3 Inducida por el Factor de Necrosis Tumoral alfa , Humanos , Egipto/epidemiología , Linfoma de Células B Grandes Difuso/epidemiología , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/metabolismo , Mutación , Factor 88 de Diferenciación Mieloide/genética , FN-kappa B/genética , FN-kappa B/metabolismo , Prevalencia , Proteína 3 Inducida por el Factor de Necrosis Tumoral alfa/genética , Proteína 3 Inducida por el Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Multidrug resistance (MDR) is still a major obstacle to chemotherapy success in acute myeloid leukemia (AML) and to a less extent acute lymphoblastic leukemia (ALL). Recent studies have shown that the expression of certain gene products mediate the development of resistance to chemotherapeutic agents. The most well characterized of these genes is the multidrug resistance gene MDR-1. This study was planned to study the expression of P-glycoprotein/170 in patients with acute leukemia and the effect of Cyclosporin A (CSA) as a modulator of P-glycoprotein functional activity. The study was carried out on 20 patients with acute leukemia (14 AML cases and 6 ALL cases). In addition, 6 normal individuals served as a reference group. Flow cytometric analysis of P-gp/170 surface expression was performed using UIC-2 MoAb together with the functional assay using Rhodamine 123 (Rh 123) and Cyclosporin A as a modulator.P-gp/170 was expressed on the leukemic cells of 37.5% of relapsed patients (40.0% of AML and 33.3% of ALL cases), whereas 27.2% of de novo patients expressed P-gp/170 (33.3% of AML cases and 0% of ALL cases). The functional activity of MDR-1 gp was 71.4% in AML and 33.3% in ALL patients compared with16.6% in normal lymphocytes. From this study, it is clear that P-gp/170 is expressed to a higher degree in leukemic cells and this is greater in relapsed compared to de novo cases and more in AML than ALL blasts. Functional activity is a more sensitive predictor of chemoresistance than P-gp/170 surface expression.