Resistance to Imatinib Mesylate-induced apoptosis in acute lymphoblastic leukemia is associated with PTEN down-regulation due to promoter hypermethylation

被引：32
|
作者：
Montiel-Duarte, Cristina [1 ]
Cordeu, Lucia [1 ]
Agirre, Xabier [1 ]
Roman-Gomez, Jose [2 ]
Jimenez-Velasco, Antonio [3 ]
Jose-Eneriz, Edurne San [1 ]
Garate, Leire [1 ]
Andreu, Enrique J. [1 ]
Calasanz, Maria Jose [4 ]
Heiniger, Anabel [3 ]
Torres, Antonio [2 ]
Prosper, Felipe [1 ]
机构：
[1] Univ Navarra, Serv Hematol, Clin Univ, Div Canc,Area Terapia Celular,Fdn Appl Med Res, Navarra 31008, Spain
[2] Hosp Reina Sofia, Dept Hematol, Cordoba, Spain
[3] Hosp Carlos Haya, Dept Hematol, Malaga, Spain
[4] Univ Navarra, Sch Sci, Dept Genet, E-31080 Pamplona, Spain
来源：
LEUKEMIA RESEARCH | 2008年 / 32卷 / 05期
关键词：
PTEN; Ph+ ALL; Imatinib; PI3K AKT;
D O I：
10.1016/j.leukres.2007.09.005
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
The aim of our study was to determine the potential mechanism(s) implicated in Imatinib resistance in patients with Ph+ ALL. Resistance of Ph+ ALL cells to Imatinib-induced apoptosis was associated with lack of inhibition of Akt phosphorylation. Addition of the PI3K inhibitor LY294002 to Imatinib significantly increased apoptosis of Ph+ ALL cells. Interestingly, expression of PTEN was reduced in Ph+ ALL cells which was due to PTEN promoter hypermethylation. Treatment of Ph+ ALL cells with 5-Aza-2'-deoxycytidine was associated with an increased expression of PTEN and an increase in cell apoptosis. These results suggest that Imatinib resistance in patients with ALL may be dependent at least in part to PTEN down-regulation due to the abnormal promoter hypermethylation and support the potential role of de-methylating agents for the treatment of patients with Ph+ ALL. (C) 2007 Elsevier Ltd. All rights reserved.
引用
收藏
页码：709 / 716
页数：8
相关论文
共 50 条
  • [11] Imatinib mesylate-induced hepato-toxicity in chronic myeloid leukemia demonstrated focal necrosis resembling acute viral hepatitis
    K Ohyashiki
    Y Kuriyama
    A Nakajima
    T Tauchi
    Y Ito
    H Miyazawa
    Y Kimura
    H Serizawa
    Y Ebihara
    Leukemia, 2002, 16 : 2160 - 2161
  • [12] Down-regulation of PTEN expression due to loss of promoter activity in human hepatocellular carcinoma cell lines
    Ma, Dong-Zhu
    Xu, Zhen
    Liang, Yu-Long
    Su, Jian-Ming
    Li, Zeng-Xia
    Zhang, Wen
    Wang, Li-Ying
    Zha, Xi-Liang
    WORLD JOURNAL OF GASTROENTEROLOGY, 2005, 11 (29) : 4472 - 4477
  • [13] Down-regulation of PTEN expression due to loss of promoter activity in human hepatocellular carcinoma cell lines
    Dong-Zhu Ma
    World Journal of Gastroenterology, 2005, (29) : 4472 - 4477
  • [14] FoxO3a gene down-regulation in pathogenesis of pediatric acute lymphoblastic leukemia
    Mirzaie, Malihe
    Nasiri, Mahboobeh
    Karimi, Mehran
    Yavarian, Majid
    Kavosi, Arghavan
    INDIAN JOURNAL OF MEDICAL AND PAEDIATRIC ONCOLOGY, 2019, 40 (03) : 381 - 385
  • [15] Prominent pleural effusion possibly due to imatinib mesylate in adult Philadelphia chromosome-positive acute lymphoblastic leukemia
    Ishii, Yuko
    Shoji, Nahoko
    Kimura, Yukihiko
    Ohyashiki, Kazuma
    INTERNAL MEDICINE, 2006, 45 (05) : 339 - 340
  • [16] Glucocorticoid-induced apoptosis and glucocorticoid resistance in acute lymphoblastic leukemia
    Ploner, C
    Schmidt, S
    Presul, E
    Renner, K
    Schröcksnadel, K
    Rainer, J
    Riml, S
    Kofler, R
    JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 2005, 93 (2-5): : 153 - 160
  • [17] Ida-FLAG plus imatinib mesylate-induced molecular remission in a patient with chemoresistant Ph1(+) acute myeloid leukemia
    Viniou, NA
    Vassilakopoulos, TP
    Giakoumi, X
    Mantzouranis, M
    Pangalis, GA
    EUROPEAN JOURNAL OF HAEMATOLOGY, 2004, 72 (01) : 58 - 60
  • [18] Synergism between the mTOR inhibitor rapamycin and FAK down-regulation in the treatment of acute lymphoblastic leukemia
    Shi, Pei-Jie
    Xu, Lu-Hong
    Lin, Kang-Yu
    Weng, Wen-Jun
    Fang, Jian-Pei
    JOURNAL OF HEMATOLOGY & ONCOLOGY, 2016, 9
  • [19] Synergism between the mTOR inhibitor rapamycin and FAK down-regulation in the treatment of acute lymphoblastic leukemia
    Pei-Jie Shi
    Lu-Hong Xu
    Kang-Yu Lin
    Wen-jun Weng
    Jian-Pei Fang
    Journal of Hematology & Oncology, 9
  • [20] Homoharringtonine-induced apoptosis of human leukemia HL-60 cells is associated with down-regulation of telomerase
    Xie, WZ
    Lin, MF
    Huang, H
    Cai, Z
    AMERICAN JOURNAL OF CHINESE MEDICINE, 2006, 34 (02): : 233 - 244
12345