P16/MTS1/INK4A gene is frequently inactivated by hypermethylation in childhood acute lymphoblastic leukemia with 11q23 translocation

M. Nakamura, K. Sugita, T. Inukai, K. Goi, K. Iijima, T. Tezuka, S. Kojika, K. Shiraishi, N. Miyamoto, N. Karakida, K. Kagami, T. O-Koyama, T. Mori, S. Nakazawa

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Abstract

The p16 gene encoding a specific inhibitor of cyclin-dependent kinases 4 and 6 has been reported to be inactivated at a variety of rates in malignant tumors. We studied frequency and mechanism of inactivation of the p16 gene in various types of childhood acute lymphoblastic leukemia (ALL) using 36 leukemic cell lines established from children (B precursor-ALL, 28; B-ALL/Burkitt's lymphoma, 3; and T-ALL, 5). On Southern blot, homozygous deletions or hemizygous deletions with rearrangement were detected in 14 cell lines. The expression of p16 protein was not observed on Western blot in 18 of 22 cell lines with intact p16 gene, but induced in 16 cell lines after treatment with the demethylating agent, indicating the silencing of the p16 gene by hypermethylation. Of note, the p16 gene was inactivated by hypermethylation of the 5' CpG island in nine of nine cell lines with 11q23 translocation, but was restored with the treatment of the demethylating agent. partial methylation of the p16 gene was also demonstrated in three of eight primary leukemia samples with this translocation, suggesting that the p16 gene inactivation by hypermethylation might play a role in the leukemogenesis and disease progression of ALL with 11q23 translocation.

Original languageEnglish
Pages (from-to)884-890
Number of pages7
JournalLeukemia
Volume13
Issue number6
DOIs
Publication statusPublished - 1999 Jan 1
Externally publishedYes

Keywords

  • 11q23 translocation
  • Acute lymphoblastic leukemia
  • p16

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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    Nakamura, M., Sugita, K., Inukai, T., Goi, K., Iijima, K., Tezuka, T., Kojika, S., Shiraishi, K., Miyamoto, N., Karakida, N., Kagami, K., O-Koyama, T., Mori, T., & Nakazawa, S. (1999). P16/MTS1/INK4A gene is frequently inactivated by hypermethylation in childhood acute lymphoblastic leukemia with 11q23 translocation. Leukemia, 13(6), 884-890. https://doi.org/10.1038/sj.leu.2401437