A20 TNFAIP3 Deletion in Epstein-Barr Virus-Associated Lymphoproliferative Disorders-LymphomasReportar como inadecuado




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A negative regulator of the nuclear factor NF-κB pathway, A20 TNFAIP3, is inactivated in several types of lymphomas; particularly in diffuse large B-cell lymphoma DLBCL, classical Hodgkin-s lymphoma, and extranodal marginal zone lymphoma of the mucosa-associated lymphoid tissue. These findings suggest that the NF-κB activation is related to A20 inactivation. Recently, A20 inactivation has also been observed in Epstein-Barr virus EBV-related lymphomas; however, this occurrence has not been well investigated. Moreover, NF-κB is a key molecule in activated B-cell-like ABC-type DLBCL; EBV-associated DLBCL is of the ABC type. Therefore, we focused on A20 deletions in EBV-associated lymphoproliferative disorders-lymphomas. Using fluorescent in situ hybridization analysis, A20 deletions were identified in 4 of 13 samples from patients with pyothorax-associated lymphoma PAL 31%, 3 of 20 samples from nasal-type NK-T cell lymphomas NKTLs 15%, 1 of 8 samples of EBV-positive DLBCL of the elderly DLBCL-e 13%, but not in any of the 11 samples from individuals with methotrexate-related lymphoproliferative disorder MTX-LPD 0%. Among the samples with A20 deletions, EBV latent membrane protein 1 LMP-1 expression was detected in all 4 of the PAL samples with A20 deletions and in the DLBCL-e sample with an A20 deletion, but not in any of the 3 NKTL samples. This finding indicated that A20 deletions were not directly related to the EBV latency pattern of lymphomas, although such deletions might be related to the diagnostic category. Immunohistologically, the A20 protein was absent in 2 15% of the13 PAL samples, 1 9% of 11 MTX-LPD samples, and in none of the 20 NKTL 0% or 8 DLBCL-e samples. In conclusion, A20 deletion and-or dysfunctional expression are frequently associated with PALs, and A20 abnormalities may be related to the pathogenesis of PAL.



Autor: Midori Ando, Yasuharu Sato , Katsuyoshi Takata, Junko Nomoto, Shigeo Nakamura, Koichi Ohshima, Tamotsu Takeuchi, Yorihisa Orita,

Fuente: http://plos.srce.hr/



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