Activated Proliferation of B-Cell Lymphomas/Leukemias with the SHP1 Gene Silencing by Aberrant CpG Methylation

作者: Maho Koyama , Takashi Oka , Mamoru Ouchida , Yoko Nakatani , Ritsuo Nishiuchi

DOI: 10.1097/01.LAB.0000106503.65258.2B

关键词:

摘要: Previously we showed reduced protein and mRNA expression of the SHP1 gene in lymphoma/leukemia cell lines patient specimens by Northern blot, RT-PCR, Western immunohistochemical analyses. In this study, aberrant methylation promoter was detected many B-cell leukemia/lymphoma as well specimens, including diffuse large lymphoma (methylation frequency 93%), MALT (82%), mantle (75%), plasmacytoma (100%) follicular (96%) methylation-specific PCR, bisulfite sequencing, restriction enzyme-mediated PCR The significantly higher high-grade cases than low-grade (70%), which correlated with no (80%) (54%). It suggests that silencing CpG relates to progression. recovered after treatment demethylating reagent: 5-aza-2'-deoxycytidine. Transfection intact hematopoietic cultured cells, show gene, induced growth inhibition, indicating plays an important role get advantage malignant cells. extraordinarily high (75 100%) indicates is one critical events onset lymphomas/leukemias implications for diagnostic or prognostic markers target therapy. These data support possibility tumor suppressor genes.

参考文章(37)
E R Maher, F M Richards, A R Webster, N A Affara, A H Prowse, F Resche, S Richard, S Olschwang, Somatic inactivation of the VHL gene in Von Hippel-Lindau disease tumors. American Journal of Human Genetics. ,vol. 60, pp. 765- 771 ,(1997)
Takashi Oka, Tadashi Yoshino, Kazuhiko Hayashi, Nobuya Ohara, Tohru Nakanishi, Yuichiro Yamaai, Akio Hiraki, Chiharu Aoki Sogawa, Eisaku Kondo, Norihiro Teramoto, Kiyoshi Takahashi, Junjiro Tsuchiyama, Tadaatsu Akagi, Reduction of Hematopoietic Cell-Specific Tyrosine Phosphatase SHP-1 Gene Expression in Natural Killer Cell Lymphoma and Various Types of Lymphomas/Leukemias: Combination Analysis with cDNA Expression Array and Tissue Microarray American Journal of Pathology. ,vol. 159, pp. 1495- 1505 ,(2001) , 10.1016/S0002-9440(10)62535-7
Boris Labar, E.A. Louwagie, E. Archimbaud, P. Stryckmans, H. Dohner, S. Suciu, Branimir Jakšić, M. Dardenne, Z. Berneman, P. Muus, R. Willemze, U. Jehn, P. Wijermans, M. Tjean, R. Zittoun, A randomized phase II study on the effects of 5-Aza-2'-deoxycytidine combined with either amsacrine or idarubicin in patients with relapsed acute leukemia: an EORTC Leukemia Cooperative Group phase II study (06893). Leukemia. ,vol. 11, ,(1997)
James G Herman, Jin Jen, Adrian Merlo, Stephen B Baylin, None, Hypermethylation-associated inactivation indicates a tumor suppressor role for p15INK4B Cancer Research. ,vol. 56, pp. 722- 727 ,(1996)
Rachel A. Katzenellenbogen, Stephen B. Baylin, James G. Herman, Hypermethylation of the DAP-Kinase CpG Island Is a Common Alteration in B-Cell Malignancies Blood. ,vol. 93, pp. 4347- 4353 ,(1999) , 10.1182/BLOOD.V93.12.4347.412K31_4347_4353
Martha M. Pao, Christina M. Bender, Peter A. Jones, Inhibition of DNA methylation by 5-aza-2'-deoxycytidine suppresses the growth of human tumor cell lines Cancer Research. ,vol. 58, pp. 95- 101 ,(1998)
Gen Tamura, A. Steven Fleisher, Stephen J. Meltzer, Manel Esteller, Tong Tong Zou, Stephen P. James, Jing Yin, Keith T. Wilson, Suna Wang, James G. Herman, Steven M. Powell, Mun Gan Rhyu, John M. Abraham, Dehe Kong, Kara N. Smolinski, Ying Qiang Shi, Hiroyuki Suzuki, Hypermethylation of the hMLH1 Gene Promoter in Human Gastric Cancers with Microsatellite Instability Cancer Research. ,vol. 59, pp. 1090- 1095 ,(1999)
Tadaatsu Akagi, Mitsune Tanimoto, Nobuya Ohara, Takehiro Tanaka, Mamoru Ouchida, Eisaku Kondo, Tadashi Yoshino, Kenji Shimizu, Kiyoshi Takahashi, Yoko Nakatani, Shinichi Takada, Takashi Oka, Maho Koyama, Kazuhiko Hayashi, Junjiro Tsuchiyama, Yoichiro Ogama, Gene Silencing of the Tyrosine Phosphatase SHP1 Gene by Aberrant Methylation in Leukemias/Lymphomas Cancer Research. ,vol. 62, pp. 6390- 6394 ,(2002)
Manel Esteller, Manel Esteller, Stephen B. Baylin, James G. Herman, Paul G. Corn, A Gene Hypermethylation Profile of Human Cancer Cancer Research. ,vol. 61, pp. 3225- 3229 ,(2001)
J Toguchida, T Sakai, N Ohtani, D W Yandell, T P Dryja, J M Rapaport, Allele-specific hypermethylation of the retinoblastoma tumor-suppressor gene. American Journal of Human Genetics. ,vol. 48, pp. 880- 888 ,(1991)