Amplification of the dihydrofolate reductase gene is a mechanism of acquired resistance to methotrexate in patients with acute lymphoblastic leukemia and is correlated with p53 gene mutations.
作者： E Goker , M Waltham , A Kheradpour , T Trippett , M Mazumdar
DOI: 10.1182/BLOOD.V86.2.677.BLOODJOURNAL862677
关键词: Gene expression 、 Gene duplication 、 Cancer research 、 Tumor suppressor gene 、 Dihydrofolate reductase 、 Molecular biology 、 Gene mutation 、 Regulation of gene expression 、 Mutation 、 Acute lymphocytic leukemia 、 Biology
摘要: Although dihydrofolate reductase (DHFR) gene amplification is a common mechanism of resistance to methotrexate (MTX) in tumor cell lines, with the exception few case reports, incidence this phenomenon as MTX clinic has not been reported. We studied 38 untreated patients and 29 relapse acute lymphoblastic leukemia (ALL) for p53 mutations. Three were both at diagnosis each two relapses after treatment MTX. Nine relapsed (31%) had low-level DHFR (two four copies) associated increased levels mRNA enzyme activity. Of significance was correlation mutations seven nine (P < .001). Low-level may be an important cause ALL strengthens concept that lead consequence defective cycle control.
ashpublications.org
bloodjournal.org参考文章(24)
Makio Wada, Claus R Bartram, Haruhiko Nakamura, Misao Hachiya, Dan-Lin Chen, Jeff Borenstein, Carl W Miller, Leopold Ludwig, Thomas E Hansen-Hagge, Wolf-Dieter Ludwig, None, Analysis of p53 mutations in a large series of lymphoid hematologic malignancies of childhood Blood. ,vol. 82, pp. 3163- 3169 ,(1993) , 10.1182/BLOOD.V82.10.3163.3163
R T Schimke, Gene amplification in cultured cells. Journal of Biological Chemistry. ,vol. 263, pp. 5989- 5992 ,(1988) , 10.1016/S0021-9258(18)68734-4
A Ichikawa, T Hotta, N Takagi, K Tsushita, T Kinoshita, H Nagai, Y Murakami, K Hayashi, H Saito, Mutations of p53 gene and their relation to disease progression in B-cell lymphoma. Blood. ,vol. 79, pp. 2701- 2707 ,(1992) , 10.1182/BLOOD.V79.10.2701.2701
Tanya M. Trippett, James T. Lin, Murray F. Brennan, Wei-Wei Li, William P. Tong, Joseph R. Bertino, Mechanisms of Natural Resistance to Antifolates in Human Soft Tissue Sarcomas Cancer Research. ,vol. 52, pp. 1434- 1438 ,(1992)
T Trippett, S Schlemmer, Y Elisseyeff, E Goker, M Wachter, P Steinherz, C Tan, E Berman, JE Wright, A Rosowsky, Defective transport as a mechanism of acquired resistance to methotrexate in patients with acute lymphocytic leukemia Blood. ,vol. 80, pp. 1158- 1162 ,(1992) , 10.1182/BLOOD.V80.5.1158.1158
Barry I. Schweitzer, Adam P. Dicker, Joseph R. Bertino, Dihydrofolate reductase as a therapeutic target The FASEB Journal. ,vol. 4, pp. 2441- 2452 ,(1990) , 10.1096/FASEBJ.4.8.2185970
Enrico Mini, Barbara A. Moroson, Christine T. Franco, Joseph R. Bertino, Cytotoxic effects of folate antagonists against methotrexate-resistant human leukemic lymphoblast CCRF-CEM cell lines. Cancer Research. ,vol. 45, pp. 325- 330 ,(1985)
Masato Orita, Youichi Suzuki, Takao Sekiya, Kenshi Hayashi, Rapid and sensitive detection of point mutations and DNA polymorphisms using the polymerase chain reaction Genomics. ,vol. 5, pp. 874- 879 ,(1989) , 10.1016/0888-7543(89)90129-8
Srinivasan Srimatkandada, William D. Medina, Arlene R. Cashmore, Wendy Whyte, Daniel Engel, Barbara A. Moroson, Christine T. Franco, Shyam K. Dube, Joseph R. Bertino, Amplification and organization of dihydrofolate reductase genes in a human leukemic cell line, K-562, resistant to methotrexate. Biochemistry. ,vol. 22, pp. 5774- 5781 ,(1983) , 10.1021/BI00294A015
Claude Caron De Fromentel, Thierry Soussi, TP53 tumor suppressor gene: a model for investigating human mutagenesis. Genes, Chromosomes and Cancer. ,vol. 4, pp. 1- 15 ,(1992) , 10.1002/GCC.2870040102