In the present study, moving from the gene expression signature that identified a a subgroup of p53wt CLL showing a lack of response to the in-vitro treatment with Nutlin-3, we eventually identified MDM4 as a gene that, despite its peculiar over-expression in a subset of Nutlin-3 ‘non-responder’ p53wt CLL, turned out to be universally over-expressed by CLL cells compared to normal B cells. This observation is in keeping with studies describing the over-expression of MDM4 in primary samples from several solid tumours, including glioblastoma, retinoblastoma, breast, colon, and lung cancers, and may contribute to identify MDM4 as a potentially useful new therapeutic target also for CLL. Preclinical studies indicating the anti-neoplastic effects of MDM4 down-regulation in murine lymphoma models are of further support for this hypothesis.
MDM4 (MDMX) is overexpressed in chronic lymphocytic leukaemia (CLL) and marks a subset of p53wild-type CLL with a poor cytotoxic response to Nutlin-3
POZZATO, GABRIELE;
2010-01-01
Abstract
In the present study, moving from the gene expression signature that identified a a subgroup of p53wt CLL showing a lack of response to the in-vitro treatment with Nutlin-3, we eventually identified MDM4 as a gene that, despite its peculiar over-expression in a subset of Nutlin-3 ‘non-responder’ p53wt CLL, turned out to be universally over-expressed by CLL cells compared to normal B cells. This observation is in keeping with studies describing the over-expression of MDM4 in primary samples from several solid tumours, including glioblastoma, retinoblastoma, breast, colon, and lung cancers, and may contribute to identify MDM4 as a potentially useful new therapeutic target also for CLL. Preclinical studies indicating the anti-neoplastic effects of MDM4 down-regulation in murine lymphoma models are of further support for this hypothesis.Pubblicazioni consigliate
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
