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.


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.


CONCLUSIONS
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.
Kondoh
Takashi
T
Department of Clinical Laboratory Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
Kobayashi
Daisuke
D
Tsuji
Naoki
N
Kuribayashi
Kageaki
K
Watanabe
Naoki
N
D000208:Acute Disease; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001483:Base Sequence; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D017931:DNA Primers; D005260:Female; D006801:Humans; D007223:Infant; D007938:Leukemia / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics*; D034741:RNA, Small Interfering; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000970:Antineoplastic Agents; D017931:DNA Primers; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D020794:Receptor Protein-Tyrosine Kinases; C482299:STYK1 protein, human