Overexpression of serine threonine tyrosine kinase 1/novel oncogene with kinase domain mRNA in patients with acute leukemia.

OBJECTIVE: Alterations in gene expression levels or mutations of previously reported tyrosine kinases are detected in only limited numbers of patients with acute leukemia. In this study, we examined whether serine threonine tyrosine kinase 1 (STYK1)/novel oncogene with kinase domain (NOK) is overexpressed in patients with acute leukemia.

MATERIALS AND METHODS: In peripheral blood cells from nonleukemic group and acute leukemic patients, STYK1/NOK messenger RNA (mRNA) expression was analyzed by quantitaive reverse transcriptase polymerase chain reaction. The effect of inhibition of STYK1/NOK mRNA on the leukemic cells was also examined.

RESULTS: When appropriate, cutoff was set using the values in nonleukemic individuals, positive STYK1/NOK expression was detected in 80.0% of leukemic patients. STYK1/NOK mRNA was highly expressed in the patients with trisomy/tetrasomy 21. mRNA expression began to decrease after chemotherapy with various drugs; this resulted in a decrease in the number of leukemic blasts in the patients' peripheral blood samples. Such changes in the gene expression were also noted in promyelocytic leukemia (M3) patients treated with all-trans retinoic acid. In addition, transfection of small inhibitory RNA against the STYK1/NOK gene into K562 cells inhibited their growth in proportion to the decrease in the mRNA expression.

CONCLUSION: These results indicate that STYK1/NOK mRNA is widely expressed in the patients with acute leukemia and suggest that inhibition of this molecule could potentially serve as a novel therapeutic target.