MYD88 L265P como factor pronóstico en Linfomas Difusos de Células Grandes B
MYD88 L265P mutation as a prognostic factor in DLBCL patients.\nIntroduction: Diffuse large B-cell lymphoma (DLBCL), the most prevalent non-Hodgkin lymphoma, is clinically and biologically heterogeneous, and up to 40% of patients are not able to reach long-term response with the use of standard ther...
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| Formato: | Tesis de maestría acceptedVersion |
| Lenguaje: | Español |
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Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica
2022
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| Acceso en línea: | http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=afamaster&cl=CL1&d=HWA_6910 https://repositoriouba.sisbi.uba.ar/gsdl/collect/afamaster/index/assoc/HWA_6910.dir/6910.PDF |
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| Sumario: | MYD88 L265P mutation as a prognostic factor in DLBCL patients.\nIntroduction: Diffuse large B-cell lymphoma (DLBCL), the most prevalent non-Hodgkin lymphoma, is clinically and biologically heterogeneous, and up to 40% of patients are not able to reach long-term response with the use of standard therapy.\nMYD88 encodes an adaptor protein of Toll-like and IL-1 receptors. The MYD88 L265P mutation is recurrently detected in DLBCL, especially in the activated B-cell subtype. Its role as a prognostic biomarker has not been clearly defined yet. In our country, there is little data on this topic.\nObjectives: To determine the prevalence and prognostic value of MYD88 L265P in an Argentine DLBCL patients retrospective cohort.\nTo assess association between overall survival and clinical or biological features in this group of patients.\nMaterials and methods: An observational retrospective cohort study was carried out, including cases with first DLBCL diagnosis at the Hospital Italiano de Buenos Aires during 2010-2016. Patients with previous history of low-grade B-Cell lymphomas or immunosuppression, special DLBCL subtypes, and cases with no available tissue for molecular techniques were excluded. Clinical features were collected from institutional electronic medical records. Immunohistochemistry for cell-of-origin classification (Hans? algorithm), and DNA extraction were carried out from formalin-fixed paraffin-embedded tissue. An in-house hydrolysis probe-based real-time PCR for the detection of MYD88 L265P was performed.\nFor overall survival analysis, only patients with comparable therapies were selected.\nResults: 67 patients were analyzed (49,3% female, median age: 66 years). According to Hans? algorithm, 40 patients (59,7%) were considered germinal center subtype, and the remaining 27 patients (40,3%) were considered non-germinal center subtype.\nThe prevalence of MYD88 L265P was 3% (IC95 0,8-10,3%) within the DLBCL cohort (1 germinal center subtype and 1 non-germinal center subtype).\n47 patients with comparable therapeutic approaches were selected for overall survival analysis. No statistically significant differences were found for localization (p=0,75), sex (p=0,82), IPI (p=0,12), stage (p=0,17), cell of origin (p=0,67) or MYD88 L265P status (p=0,31). A shorter overall survival was found in ?60-year-old patients (p=0,047).\nDiscussion and conclusion: Within the analyzed cohort, the number of MD88 L265P-positive cases was surprisingly low (n=2). Our finding was different as compared with the meta-analysis published in 2017 by Lee and colleagues (MYD88 L265P prevalence 16,5%; p=0,001). We could hypothesize that other mutations could be involved in NF-kB activation in non-germinal center DLBCLs, possibly due to population-related predisposition or environmental factors. Neither MYD88 L265P nor cell of origin subtypes were associated with a shortened overall survival. Only the ?60-year-old patients showed a diminished overall survival, being this comparable with international publications.\nThe obtained results are interesting and set out new hypotheses for further investigations. |
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