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Leuk Lymphoma. 2016 Oct;57(10):2330-41. doi: 10.3109/10428194.2016.1144880. Epub 2016 Feb 16.

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).

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a Department of Internal Medicine , University Hospital for Internal Medicine V (Haematology and Oncology), Medical University of Innsbruck , Innsbruck , Austria ;
b Area 4 Health Technology Assessment and Bioinformatics , ONCOTYROL - Center for Personalized Cancer Medicine , Innsbruck , Austria ;
c Tyrolean Cancer Research Institute , Innsbruck , Austria ;
d Laboratory of Immunological and Molecular Cancer Research , Salzburg Cancer Research Institute , Salzburg , Austria ;
e Department of Pathology, Division of General Pathology , Medical University of Innsbruck , Innsbruck , Austria.


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.


Autophagy; Beclin-1; IMiDs; biomarkers; multiple myeloma

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