plays critical roles in disease progression and response to cytarabine in AML.

Lysine methyltransferase 2A (, also known as ) translocations (‑t) are frequently associated with mutations in pathway genes in acute myeloid leukemia (AML). Previous findings with a mouse model showed that cooperation of with tyrosine‑protein phosphatase non‑receptor type 11  accelerated leukemia development, but increased cytarabine (Ara‑C) sensitivity of leukemia cells. To identify the genes responsible for reduced survival and Ara‑C resistance, transcriptomic profiling between six pairs of mouse leukemia cells harboring activating and wild‑type or was compared. A total of 23 differentially expressed genes (DEGs) with >1.5‑fold‑change between the paired cell lines were identified. The Gene Ontology (GO) terms overrepresented in these 23 DEGs included 'immune system process', 'actin filament binding', 'cellular response to interferon‑alpha' and 'sequence‑specific DNA'. Among the four genes (, PR domain zinc finger protein 5, Iroquois‑class homeodomain protein IRX‑5 and homeobox protein PKNOX2) mapped to the GO term 'sequence‑specific DNA', upregulation was associated with AML harboring ‑t and signaling mutations based on a meta‑analysis using data deposited in Oncomine™ and analysis of the clinical samples in the present study. Microarray data revealed that only was upregulated in those cells harboring activating . Functional studies of knockdown or overexpression in cells revealed that expression levels were associated with survival and Ara‑C sensitivity/apoptosis . In addition, regulated the expression of the apoptosis‑related genes, NF‑κB inhibitor α, transcription factor p65 and transformation‑related protein p53. Furthermore, the results of a meta‑analysis using Heuser's AML dataset supported the finding that chemotherapy responders have higher expression levels of . These results indicated that the expression of increased cell apoptosis and predicted an improved response to Ara‑C in AML.