Promoter hypermethylation of cancer-related genes: a strong independent prognostic factor in acute lymphoblastic leukemia.
作者： Jose Roman-Gomez , Antonio Jimenez-Velasco , Juan A Castillejo , Xabier Agirre , Manuel Barrios
DOI: 10.1182/BLOOD-2004-03-0954
关键词:
摘要: Promoter hypermethylation plays an important role in the inactivation of cancer-related genes. This abnormality occurs early leukemogenesis and seems to be associated with poor prognosis acute lymphoblastic leukemia (ALL). To determine extent ALL, we analyzed methylation status CDH1, p73, p16, p15, p57, NES-1, DKK-3, CDH13, p14, TMS-1, APAF-1, DAPK, PARKIN, LATS-1, PTEN genes 251 consecutive ALL patients. A total 77.3% samples had at least 1 gene methylated, whereas 35.9% cases 4 or more methylated. Clinical features complete remission rate did not differ among patients without methylated genes, 3 (methylated group A), than B). Estimated disease-free survival (DFS) overall (OS) 11 years were 75.5% 66.1%, respectively, for nonmethylated group; 37.2% 45.5% A; 9.4% 7.8% B (P < .0001 P = .0004, respectively). Multivariate analysis demonstrated that profile was independent prognostic factor predicting DFS .0001) OS .003). Our results suggest may a potential new biomarker risk prediction ALL.
ashpublications.org
bloodjournal.org参考文章(39)
John R. Melki, Paul C. Vincent, Ross D. Brown, Susan J. Clark, Hypermethylation of E-cadherin in leukemia. Blood. ,vol. 95, pp. 3208- 3213 ,(2000) , 10.1182/BLOOD.V95.10.3208
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
Stefan Faderl, Hagop M. Kantarjian, Moshe Talpaz, Zeev Estrov, Clinical Significance of Cytogenetic Abnormalities in Adult Acute Lymphoblastic Leukemia Blood. ,vol. 91, pp. 3995- 4019 ,(1998) , 10.1182/BLOOD.V91.11.3995.411A43_3995_4019
Peter A. Jones, Stephen B. Baylin, The fundamental role of epigenetic events in cancer Nature Reviews Genetics. ,vol. 3, pp. 415- 428 ,(2002) , 10.1038/NRG816
Gerard I. Evan, Karen H. Vousden, Proliferation, cell cycle and apoptosis in cancer Nature. ,vol. 411, pp. 342- 348 ,(2001) , 10.1038/35077213
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
Steven M. Kornblau, Guillermo Garcia-Manero, Hagop M. Kantarjian, Terry L. Smith, Jerry Daniel, Jean Pierre J Issa, Ming Sheng Lee, DNA methylation of multiple promoter-associated CpG islands in adult acute lymphocytic leukemia. Clinical Cancer Research. ,vol. 8, pp. 2217- 2224 ,(2002)
Gabriel Capella, Minoru Toyota, Manel Esteller, Stephen B. Baylin, Miguel Angel Peinado, James G. Herman, Silvia Tortola, Hypermethylation-associated Inactivation of p14ARF Is Independent of p16INK4a Methylation and p53 Mutational Status Cancer Research. ,vol. 60, pp. 129- 133 ,(2000)
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 Besalduch, M Fontanillas, S Brunet, JF San Miguel, J Garcia-Conde, JM Ribera, A Oriol, J Maldonado, JJ Ortega, J Zuazu, E Feliu, S Gardella, J Macia, P Leon, JM Hernandez-Rivas, A Domingo-Albos, Late intensification chemotherapy has not improved the results of intensive chemotherapy in adult acute lymphoblastic leukemia. Results of a prospective multicenter randomized trial (PETHEMA ALL-89). Spanish Society of Hematology Haematologica. ,vol. 83, pp. 222- 230 ,(1998) , 10.3324/%X