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

被引:30
作者
Kondoh, Takashi [1 ]
Kobayashi, Daisuke [1 ]
Tsuji, Naoki [1 ]
Kuribayashi, Kageaki [1 ]
Watanabe, Naoki [1 ]
机构
[1] Sapporo Med Univ, Sch Med, Dept Clin Lab Med, Chuo Ku, Sapporo, Hokkaido 0608543, Japan
基金
日本学术振兴会;
关键词
ACUTE LYMPHOBLASTIC-LEUKEMIA; DIAGNOSTIC RELEVANCE; NUDE-MICE; NOK; TUMORIGENESIS; EXPRESSION; RESISTANCE; INHIBITOR; IMATINIB; CELLS;
D O I
10.1016/j.exphem.2009.04.010
中图分类号
R5 [内科学];
学科分类号
100201 [内科学];
摘要
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 I (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. (C) 2009 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.
引用
收藏
页码:824 / 830
页数:7
相关论文
共 17 条
[1]
Diagnostic relevance of overexpressed mRNA of novel oncogene with kinase-domain (NOK) in lung cancers [J].
Amachika, Tomoko ;
Kobayashi, Daisuke ;
Moriai, Ryosuke ;
Tsuji, Naoki ;
Watanabe, Naoki .
LUNG CANCER, 2007, 56 (03) :337-340
[2]
Point mutation at single tyrosine residue of novel oncogene NOK abrogates tumorigenesis in nude mice [J].
Chen, Y ;
Li, YH ;
Chen, XP ;
Gong, LN ;
Zhang, SP ;
Chang, ZJ ;
Zhang, XF ;
Fu, XY ;
Liu, L .
CANCER RESEARCH, 2005, 65 (23) :10838-10846
[3]
The novel Akt inhibitor, perifosine, induces caspase-dependent apoptosis and downregulates P-glycoprotein expression in multidrug-resistant human T-acute leukemia cells by a JNK-dependent mechanism [J].
Chiarini, F. ;
Del Sole, M. ;
Mongiorgi, S. ;
Gaboardi, G. C. ;
Cappellini, A. ;
Mantovani, I. ;
Follo, M. Y. ;
McCubrey, J. A. ;
Martelli, A. M. .
LEUKEMIA, 2008, 22 (06) :1106-1116
[4]
Ezzat S, 2002, J CLIN INVEST, V109, P69, DOI 10.1172/JCI200214036
[5]
Molecular mechanisms of resistance to imatinib in Philadelphia-chromosome-positive leukaemias [J].
Gambacorti-Passerini, CB ;
Gunby, RH ;
Piazza, R ;
Galietta, A ;
Rostagno, R ;
Scapozza, L .
LANCET ONCOLOGY, 2003, 4 (02) :75-85
[6]
Cotreatment with 17-allylamino-demethoxygeldanamycin and FLT-3 kinase inhibitor PKC412 is highly effective against human acute myelogenous leukemia cells with mutant FLT-3 [J].
George, P ;
Bali, P ;
Cohen, P ;
Tao, JG ;
Guo, F ;
Sigua, C ;
Vishvanath, A ;
Fiskus, W ;
Scuto, A ;
Annavarapu, S ;
Moscinski, L ;
Bhalla, K .
CANCER RESEARCH, 2004, 64 (10) :3645-3652
[8]
Incidence of TEL/AML1 fusion gene analyzed consecutively in children with acute lymphoblastic leukemia in relapse [J].
Harbott, J ;
Viehmann, S ;
Borkhardt, A ;
Henze, G ;
Lampert, F .
BLOOD, 1997, 90 (12) :4933-4937
[9]
Endogenous tumor necrosis factor as a predictor of doxorubicin sensitivity in leukemic patients [J].
Kobayashi, D ;
Watanabe, N ;
Yamauchi, N ;
Tsuji, N ;
Sato, T ;
Niitsu, Y .
BLOOD, 1997, 89 (07) :2472-2479
[10]
A novel protein tyrosine kinase NOK that shares homology with platelet-derived growth factor/fibroblast growth factor receptors induces tumorigenesis and metastasis in nude mice [J].
Liu, L ;
Yu, XZ ;
Li, TS ;
Song, LX ;
Chen, PL ;
Suo, TL ;
Li, YH ;
Wang, SD ;
Chen, Y ;
Ren, YM ;
Zhang, SP ;
Chang, ZJ ;
Fu, XY .
CANCER RESEARCH, 2004, 64 (10) :3491-3499