The Lysine Methyltransferase SMYD2 is Required for Normal Lymphocyte Development and Survival of Hematopoietic Leukemias

Overview

Journal Genes Immun

Date 2020 Mar 3

PMID 32115575

Citations 6

Authors

Mark A Brown

Melissa A Edwards

Ilham Alshiraihi

Huimin Geng

Joseph D Dekker

Haley O Tucker

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

SMYD family in cancer: epigenetic regulation and molecular mechanisms of cancer proliferation, metastasis, and drug resistance.

Han T, Kim D, Son M, Cho H Exp Mol Med. 2024; 56(11):2325-2336.

PMID: 39482529 PMC: 11611910. DOI: 10.1038/s12276-024-01326-8.

Targeting Epigenetic Changes Mediated by Members of the SMYD Family of Lysine Methyltransferases.

Padilla A, Manganaro J, Huesgen L, Roess D, Brown M, Crans D Molecules. 2023; 28(4).

PMID: 36838987 PMC: 9967872. DOI: 10.3390/molecules28042000.

Mechanistic and functional extrapolation of SET and MYND domain-containing protein 2 to pancreatic cancer.

Alshammari E, Zhang Y, Yang Z World J Gastroenterol. 2022; 28(29):3753-3766.

PMID: 36157542 PMC: 9367238. DOI: 10.3748/wjg.v28.i29.3753.

The SMYD family proteins in immunology: An update of their obvious and non-obvious relations with the immune system.

Rubio-Tomas T Heliyon. 2021; 7(6):e07387.

PMID: 34235289 PMC: 8246384. DOI: 10.1016/j.heliyon.2021.e07387.

The Lysine Methyltransferase SMYD2 Is Required for Definite Hematopoietic Stem Cell Production in the Mouse Embryo.

Edwards M, Brown M, Alshiraihi I, Jarrell D, Tucker H Vet Sci. 2020; 7(3).

PMID: 32722433 PMC: 7560092. DOI: 10.3390/vetsci7030100.

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