Low Beclin-1 expression predicts improved overall survival in patients treated with immunomodulatory drugs for multiple myeloma and identifies autophagy inhibition as a promising potentially druggable new therapeutic target: an analysis from The Austrian Myeloma Registry (AMR).
Leuk Lymphoma
; 57(10): 2330-41, 2016 10.
Article
em En
| MEDLINE
| ID: mdl-26880040
ABSTRACT
Beclin-1 is a key regulator of autophagy and has been suggested to be involved in the development of drug resistance in multiple myeloma (MM). We analyzed the expression of Beclin-1 in a retrospective cohort of 70 MMs. Beclin-1 expression did not influence overall survival (OS) and progression-free survival (PFS) in patients with therapy-naïve MM. In patients treated with immunomodulatory drugs (IMiDs) lack of or low Beclin-1 expression resulted in a significantly improved OS and PFS compared to those treated with bortezomib or nonnovel agents. Beclin-1 expression was more frequently detected in relapsed MM than in therapy-naïve MM probably being a hallmark of tumor progression and therapy resistance. If validated prospectively, Beclin-1 expression might identify patients prone to profit above average from IMiDs and enable a more rational allocation of antimyeloma therapies. Furthermore, the inhibition of autophagy could be a new promising target to improve response to treatment in the relapsed/refractory setting.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Expressão Gênica
/
Proteína Beclina-1
/
Fatores Imunológicos
/
Mieloma Múltiplo
/
Antineoplásicos
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
/
Aged
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article