Research Papers:

Identification and validation of the dopamine agonist bromocriptine as a novel therapy for high-risk myelodysplastic syndromes and secondary acute myeloid leukemia

Fabio Giuseppe Liberante _, Tara Pouryahya, Mary-Frances McMullin, Shu-Dong Zhang and Kenneth Ian Mills

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Oncotarget. 2016; 7:6609-6619. https://doi.org/10.18632/oncotarget.6773

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Fabio Giuseppe Liberante1, Tara Pouryahya1, Mary-Frances McMullin1, Shu-Dong Zhang1,*, Kenneth Ian Mills1,*

1Centre for Cancer Research and Cell Biology (CCRCB), Queen's University Belfast, Belfast, United Kingdom

*These authors contributed equally to this work

Correspondence to:

Fabio Giuseppe Liberante, e-mail: [email protected]

Keywords: myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), bromocriptine, re-purposed, therapy

Received: July 03, 2015     Accepted: November 28, 2015     Published: December 28, 2015


Myelodysplastic syndromes (MDS) represent a broad spectrum of diseases characterized by their clinical manifestation as one or more cytopenias, or a reduction in circulating blood cells. MDS is predominantly a disease of the elderly, with a median age in the UK of around 75. Approximately one third of MDS patients will develop secondary acute myeloid leukemia (sAML) that has a very poor prognosis. Unfortunately, most standard cytotoxic agents are often too toxic for older patients. This means there is a pressing unmet need for novel therapies that have fewer side effects to assist this vulnerable group. This challenge was tackled using bioinformatic analysis of available transcriptomic data to establish a gene-based signature of the development and progression of MDS. This signature was then used to identify novel therapeutic compounds via statistically-significant connectivity mapping. This approach suggested re-purposing an existing and widely-prescribed drug, bromocriptine as a novel potential therapy in these disease settings. This drug has shown selectivity for leukemic cells as well as synergy with current therapies.

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