SETD4 as a marker of disease burden and treatment response in childhood acute lymphoblastic leukemia

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 the KMT SMYD2 has been identified as a prognostic marker in ALL, SETD4 remains poorly characterized. The present study analyzed the expression patterns of SETD4 in 83 pediatric ALL patients at diagnosis and during treatment using reverse transcription‑quantitative PCR. Kaplan‑Meier analysis was employed to evaluate survival outcomes between the high and basal SETD4 expression groups. It was found that SETD4 expression is markedly upregulated in bone marrow (BM) samples derived from ALL patients compared with 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. The present study further investigated whether SETD4 levels are associated with those of SMYD2. Notably, a positive correlation between both genes was observed at diagnosis (Spearman ρ=0.759, P<0.0001), with a substantial correlation persisting throughout treatment (Spearman ρ=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. The findings revealed the involvement of SETD4 in leukemogenesis and highlighted its potential as a promising prognostic marker.