学術雑誌論文 Aberrant DNA methylation is associated with a poor outcome in Juvenile myelomonocytic leukemia

Sakaguchi, Hirotoshi  ,  Muramatsu, Hideki  ,  Okuno, Yusuke  ,  Makishima, Hideki  ,  Xu, Yinyan  ,  Furukawa-Hibi, Yoko  ,  Wang, Xinan  ,  Narita, Atsushi  ,  Yoshida, Kenichi  ,  Shiraishi, Yuichi  ,  Doisaki, Sayoko  ,  Yoshida, Nao  ,  Hama, Asahito  ,  Takahashi, Yoshiyuki  ,  Yamada, Kiyofumi  ,  Miyano, Satoru  ,  Ogawa, Seishi  ,  Maciejewski, Jaroslaw P.  ,  Kojima, Seiji

10 ( 12 ) 2015-12-31 , Public Library of Science
ISSN:1932-6203
内容記述
Juvenile myelomonocytic leukemia (JMML), an overlap of myelodysplastic/myeloproliferative neoplasm, is an intractable pediatric myeloid neoplasm. Epigenetic regulation of transcription, particularly by CpG methylation, plays an important role in tumor progression, mainly by repressing tumor-suppressor genes. To clarify the clinical importance of aberrant DNA methylation, we studied the hypermethylation status of 16 target genes in the genomes of 92 patients with JMML by bisulfite conversion and the pryosequencing technique. Among 16 candidate genes, BMP4, CALCA, CDKN2A, and RARB exhibited significant hypermethylation in 72% (67/92) of patients. Based on the number of hypermethylated genes, patients were stratified into three cohorts based on an aberrant methylation score (AMS) of 0, 1-2, or 3-4. In the AMS 0 cohort, the 5-year overall survival (OS) and transplantation-free survival (TFS) were good (69% and 76%, respectively). In the AMS 1-2 cohort, the 5-year OS was comparable to that in the AMS 0 cohort (68%), whereas TFS was poor (6%). In the AMS 3-4 cohort, 5-year OS and TFS were markedly low (8% and 0%, respectively). Epigenetic analysis provides helpful information for clinicians to select treatment strategies for patients with JMML. For patients with AMS 3-4 in whom hematopoietic stem cell transplantation does not improve the prognosis, alternative therapies, including DNA methyltransferase inhibitors and new molecular-targeting agents, should be established as treatment options.
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http://repository.kulib.kyoto-u.ac.jp/dspace/bitstream/2433/210540/1/journal.pone.0145394.pdf

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