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Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RAPID COMMUNICATION Hypermethylation of the p15INK4B Gene in Myelodysplastic Syndromes Toshiki Uchida, Tomohiro Kinoshita, Hirokazu Nagai, Yohsuke Nakahara, Hidehiko Saito, Tomomitsu Hotta, and Takashi Murate From the First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan; and the Fourth Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan. Previous studies have shown that the cyclin-dependent kinase inhibitor (CDKI) genes p15INK4B and p16INK4A are frequently inactivated by genetic alterations in many malignant tumors and that they are candidate tumor-suppressor genes. Although genetic alterations in these genes may be limited to lymphoid malignancies, it has been reported that their inactivation by aberrant methylation of 5' CpG islands may be involved in various hematologic malignancies. In this study, we investigated the p15INK4B and p16INK4A genes to clarify their roles in the pathogenesis of myelodysplastic syndrome (MDS). Southern blotting analysis showed no gross genetic alterations in either of these genes. However, hypermethylation of the 5' CpG island of the p15INK4B gene occurred frequently in patients with MDS (16/32 [50%]). Interestingly, the p15INK4B gene was frequently methylated in patients with high-risk MDS (refractory anemia with excess blasts [RAEB], RAEB in transformation [RAEB-t], and overt leukemia evolved from MDS; 14/18 [78%]) compared with patients with low-risk MDS (refractory anemia [RA] and refractory anemia with ring sideroblast [RARS]; 1/12 [8%]). Furthermore, methylation status of the p15INK4B gene was progressed with the development of MDS in most patients examined. In contrast, none of the MDS patients showed apparent hypermethylation of the p16INK4A gene. These results suggest that hypermethylation of the p15INK4B gene is involved in the pathogenesis of MDS and is one of the important late events during the development of MDS. Blood, Vol. 90 No. 4 (August 15), 1997: pp. 1403-1409 © 1997 by The American Society of Hematology. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Y. Satoh, I. Matsumura, H. Tanaka, S. Ezoe, K. Fukushima, M. Tokunaga, M. Yasumi, H. Shibayama, M. Mizuki, T. Era, et al. AML1/RUNX1 Works as a Negative Regulator of c-Mpl in Hematopoietic Stem Cells J. Biol. Chem., October 31, 2008; 283(44): 30045 - 30056. [Abstract] [Full Text] [PDF] R. B. Klisovic, W. Stock, S. Cataland, M. I. Klisovic, S. Liu, W. Blum, M. Green, O. Odenike, L. Godley, J. V. Burgt, et al. A Phase I Biological Study of MG98, an Oligodeoxynucleotide Antisense to DNA Methyltransferase 1, in Patients with High-Risk Myelodysplasia and Acute Myeloid Leukemia Clin. 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