Open AccessThe lysine methyltransferase SMYD2 is required for normal lymphocyte development and survival of hematopoietic leukemias
Author(s) -
Mark A. Brown,
Melissa A. Edwards,
Ilham Alshiraihi,
Huimin Geng,
Joseph D. Dekker,
Haley O. Tucker
Publication year - 2020
Publication title -
genes and immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.35
H-Index - 100
eISSN - 1476-5470
pISSN - 1466-4879
DOI - 10.1038/s41435-020-0094-8
Subject(s) - biology , haematopoiesis , leukemia , methyltransferase , cancer research , oncogene , cell cycle , lymphopoiesis , jurkat cells , microbiology and biotechnology , immunology , apoptosis , stem cell , genetics , t cell , immune system , methylation , gene
The five membered SET and MYND Domain-containing lysine methyltransferase (SMYD) family plays pivotal roles in development and proliferation. Initially characterized within the cardiovascular system, one such member, SMYD2, has been implicated as an oncogene in leukemias deriving from flawed hematopoietic stem cell (HSC) differentiation. We show here that conditional SMYD2 loss disrupts hematopoiesis at and downstream of the HSC via both apoptotic loss and transcriptional deregulation of HSC proliferation and disruption of Wnt-β-Catenin signaling. Yet, previously documented SMYD2 cell cycle targets were unscathed. Turning our analysis to human leukemias, we observed that SMYD2 is highly expressed in CML, MLLr-B-ALL, AML, T-ALL, and B-ALL leukemias and its levels in B-ALL correlate with poor survival. SMYD2 knockdown results in apoptotic death and loss of anchorage-independent transformation of each of these hematopoietic leukemias. These data provide an underlying mechanism by which SMYD2 acts during normal hematopoiesis and as a proto-oncogene in leukemia.