SMYD2 in Leukemia: An Update

Abstract

SMYD2 is one of the five members (SMYD1-5) of the Su(Var)3-9, Enhancer-of-zeste and Trithorax (SET) and Myeloid, Nervy, and DEAF-1 (MYND) domain-containing (SMYD) protein family and is it known to methylate histone and non-histone substrates. By methylating a wide range of targets, SMYD2 acts as an oncogene in most cancer types. In this review I will comment on the last publications related to the role of SMYD2 in leukemia and I will refer to more extensive reviews if the reader aims to have a broader picture of the state of the art. *Corresponding author: Teresa Rubio-Tomás, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; School of Medicine, University of Crete, Crete, Greece Check for updates SMYD2 Promotes Leukemia Progression Remarkably, SMYD2 is not only involved in leukemia, but also normal lineage differentiation of hematopoietic stem cells, since mice lacking SMYD2 specifically in hematopoietic stem cells displayed aberrant lymphocyte development. Regarding leukemia, these SMYD2 knockout mice had a high rate of apoptosis and showed loss of anchorage-independent transformation of leukemia cells [1]. In line with these observations, the authors detected overexpression of SMYD2 in many types of human leukemia [1]. Even residual expression of SMYD2 (and SMYD3) can promote chronic lymphocytic leukemia, probably due to the acquisition of complex karyotype [2]. Zipin-Roitman, et al. observed that decreased expression of SMYD2 leads to overexpression of SET7/9, indicating some kind of interplay between these two methyl transferases, that results in higher resistance to DNA damage of leukemia cells [3]. In addition, SMYD2 seemed to be downstream of MYC in acute myeloid leukemia [4]. ISSN: 2469-5696 DOI: 10.23937/2469-5696/1410067 Tomás. Int J Blood Res Disord 2021, 8:067 • Page 2 of 2 • 5. Ping Z, Ruan JF, Weng W, Tang Y (2020) Overexpression of SET and MYND domain-containing protein 2 (SMYD2) is associated with poor prognosis in pediatric b lineage acute lymphoblastic leukemia. Leuk Lymphoma 61: 437-444. 6. Sakamoto LHT, Andrade RV, Felipe MSS, Motoyama AB, Silva FP, et al. (2014) SMYD2 is highly expressed in pediatric acute lymphoblastic leukemia and constitutes a bad prognostic factor. Leuk Res 38: 496-502. 7. Xin Y, Jiang XJ, Fang ZM (2019) HSistone methyltransferase SMYD2: Ubiquitous regulator of disease. Clinical Epigenetics 11: 112. 8. Edoardo F, Manoni E, Ferroni C, Del Rio A, Bartolini M (2019) Small-molecule inhibitors of lysine methyltransferases SMYD2 and SMYD3: Current trends. Future Medicinal Chemistry 11: 901-921. 9. Teresa R-T (2021) The SMYD family proteins in immunology: An update of their obvious and non-obvious relations with the immune system. Heliyon 7: e07387.