BCR-ABL-mediated regulation of SH3BGRL2, D53, PRAME, DAP12 e Calcineurin A beta and biological consequences of this regulation on CML. / Regulação da expressão de SH3BGRL2, D53, PRAME, DAP12 e calcineurina A beta por BCR-ABL e consequências biológicas dessa regulação na LMC.

AUTOR(ES)

Daniel Diniz de Carvalho

DATA DE PUBLICAÇÃO

2009

RESUMO

TRAIL was shown to selectively kill tumor cells. Not surprisingly, TRAIL is down-regulated in a variety of tumor cells, but the mechanism responsible for TRAIL inhibition remains elusive. Because TRAIL can be regulate by retinoic acid; PRAME was shown to inhibit transcription of retinoic acid receptor target genes through the polycomb protein EZH2; and we have found that TRAIL is inversely correlated with BCR-ABL in CML patients, we decided to investigate the association of PRAME, EZH2 and TRAIL in BCR-ABL-positive leukemia. Here, we demonstrate that PRAME, but not EZH2, is up-regulated in BCR-ABL cells and is associated with the progression of disease in CML patients. In addition, PRAME expression is positively correlated with BCR-ABL and negatively with TRAIL in these patients. Importantly, knocking down of PRAME or EZH2 by RNA interference restores TRAIL expression. Our data reveal a novel regulatory mechanism responsible for lowering TRAIL expression and provide the basis of alternative targets for combined therapeutic strategies for CML.

ASSUNTO(S)

trail trail prame apoptosis ezh2 apoptose gene expression (regulation) leucemia mielóide crônica cultured tumor cells bcr-abl chronic myeloid leukemia bcr-abl expressão gênica (regulação) células cultivadas de tumor ezh2 prame

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