Oncotarget

Priority Research Papers:

Smyd2 is a Myc-regulated gene critical for MLL-AF9 induced leukemogenesis

Sevgi Bagislar, Arianna Sabò, Theresia R. Kress, Mirko Doni, Paola Nicoli, Stefano Campaner and Bruno Amati _

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Oncotarget. 2016; 7:66398-66415. https://doi.org/10.18632/oncotarget.12012

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Abstract

Sevgi Bagislar1, Arianna Sabò2, Theresia R. Kress2, Mirko Doni1, Paola Nicoli1, Stefano Campaner2 and Bruno Amati1,2

1 Department of Experimental Oncology, European Institute of Oncology, Milan, Italy

2 Center for Genomic Science of IIT at SEMM, Fondazione Istituto Italiano di Tecnologia, Milan, Italy

Correspondence to:

Bruno Amati, email:

Keywords: MLL-AF9, acute myeloid leukemia, Smyd2, c-Myc, lymphoma

Received: July 18, 2016 Accepted: September 07, 2016 Published: September 13, 2016

Abstract

The Smyd2 protein (Set- and Mynd domain containing protein 2) is a methyl-transferase that can modify both histones and cytoplasmic proteins. Smyd2 is over-expressed in several cancer types and was shown to be limiting for tumor development in the pancreas. However, genetic evidence for a role of Smyd2 in other cancers or in mouse development was missing to date. Using germ line-deleted mouse strains, we now show that Smyd2 and the related protein Smyd3 are dispensable for normal development. Ablation of Smyd2 did not affect hematopoiesis, but retarded the development of leukemia promoted by MLL-AF9, a fusion oncogene associated with acute myeloid leukemia (AML) in humans. Smyd2-deleted leukemic cells showed a competitive disadvantage relative to wild-type cells, either in vitro or in vivo. The Smyd2 gene was directly activated by the oncogenic transcription factor Myc in either MLL9-AF9-induced leukemias, Myc-induced lymphomas, or fibroblasts. However, unlike leukemias, the development of lymphomas was not dependent upon Smyd2. Our data indicate that Smyd2 has a critical role downstream of Myc in AML.


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