Expression and prognostic significance of chromatin modulators EHMT2/G9a and KDM2b in acute myeloid leukemia

Abstract

Epigenetics factors are critical for normal cell function and their regulation is sensitive to malignancy development. EHMT2/G9a and KDM2b are key epigenetics players in different cancer types. However, their expression profiles and related consequences in acute myeloid leukemia (AML) patients have not been known yet. In addition to routine lab work, expression levels of EHMT2/G9a and KDM2b were determined in 110 adult and pediatric patients with De Novo AML. Relations between their expression and patients' clinical data were tested by statistical methods. EHMT2/G9a and KDM2b were highly expressed in AML patients against control cases and associated with the presence of adverse genomic alterations. In response to induction chemotherapy, EHMT2/G9a and KDM2b showed to be significantly high in resistant and relapsed patients in comparison to the complete remission group. KDM2b overexpression was associated with CD11c (integrin alpha X) downregulation. Kaplan−Meier analysis indicated that EHMT2/G9a and KDM2b overexpression was correlated with poor survival status in AML patients. We conclude that EHMT2/G9a and KDM2b expression levels could be used as independent prognostic factors for AML disease.

The Role and Mechanism of the Histone Methyltransferase G9a in Tumors: Update

“…In response to induction chemotherapy, G9a and KDM2B are significantly higher in patients with drug resistance and relapse than in complete remission patients. 60 G9a has also been associated with acute lymphoblastic leukemia (ALL), and its inhibition promotes lysosome biogenesis, which inhibits the metabolic sensor sestrin 2 (SESN2), represses glycogen synthase kinase-3 (GSK-3)-related autophagic degradation, and ultimately impairs glycogen metabolism. 61 Moreover, G9a targets the tumor suppressor factor SRY-box transcription factor 6 (SOX6), therefore, targeting G9a to upregulate SOX6 can inhibit self-renewal ability in chronic myeloid leukemia (CML).…”

Drivers of de novo Serine/Glycine synthesis in acute leukemia

“…EHMT2 upregulates transcription of the SSP genes by H3K9 mono-methylation leading to enhanced de novo serine/glycine synthesis (25). Interestingly, increased EHMT2 expression and H3K9me1 levels are also seen in acute myeloid leukemia (AML) (26,27). Additionally, in T-ALL cells EHMT2 suppresses p53 levels (24), a known suppressor of PHGDH expression and the SSP in melanoma (28), which is also targeted by mutations in T-ALL (29).…”