SETD4 expression is correlated with leukemic burden and SMYD2 transcription in acute lymphoblastic leukemia

Background Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy worldwide. Despite a good rate of treatment success, the poor prognosis underscores the urgent need for new prognostic markers and effective therapeutic strategies. The SET family of lysine methyltransferases (KMTs) has been implicated in several cancers. While SMYD2 has been identified as a prognostic marker in ALL, SETD4 is a member that is still poorly characterized. Methods In the present study, we analyzed the expression patterns of SETD4 in 83 pediatric ALL patients at diagnosis and during treatment using RT‒ qPCR. Kaplan-Meier analysis was employed to evaluate survival outcomes between the high and basal SETD4 expression groups. Results We found that SETD4 transcription levels are significantly upregulated in BM samples derived from ALL patients compared to non-neoplastic BM (median fold-change of 5.14 p = 0.0095) and SETD4 expression is correlated with leukemic burden. Importantly, the levels of SETD4 decreased in chemotherapy-responsive patients. We further investigated whether SETD4 transcription levels are associated with those of SMYD2 . Notably, a positive correlation between both genes was observed at diagnosis (Spearman r = 0.759, p < 0.0001), with a substantial correlation persisting throughout treatment (Spearman r = 0.925, p < 0.01). Furthermore, patients classified in the high-risk category exhibited elevated SETD4 expression, with those displaying high SETD4 transcription exhibiting the poorest survival outcomes. Conclusion Our findings unveil the involvement of SETD4 in leukemogenesis and highlight its potential as a promising prognostic marker.