Restriction landmark genome scanning for aberrant methylation in primary refractory and relapsed acute myeloid leukemia involvement of the WIT-1 gene

Christoph Plass, Feng Yu, Li Yu, Matthew P. Strout, Wa'el El-Rifai, Erkki Elonen, Sakari Knuutila, Guido Marcucci, Donn C. Young, William A. Held, Clara D. Bloomfield, Michael A. Caligiuri

Research output: Contribution to journalArticle

52 Scopus citations

Abstract

There is substantial evidence to suggest that aberrant DNA methylation in the regulatory regions of expressed genes may play a role in hematologic malignancy. In the current report, the Restriction Landmark Genomic Scanning (RLGS) method was used to detect aberrant DNA methylation (M) in acute myeloid leukemia (AML). RLGS-M profiles were initially performed using DNA from diagnostic, remission, and relapse samples from a patient with AML. Rp18, one of the eight spots found that was absent in the relapse sample, was cloned. Sequence analysis showed that the spot represented a portion of the WIT-1 gene on human chromosome 11p13. Rp18 was missing in the relapse sample due to a distinct DNA methylation pattern of the WIT-1 gene. Twenty-seven AML patients that entered CR after therapy (i.e., chemosensitive) were studied and only 10 (37%) of the diagnostic bone marrow (BM) samples showed methylation of WIT-1. However, seven of eight (87.5%) diagnostic BM samples from primary refractory AML (chemosensitive) showed methylation of WIT-1. The incidence of WIT-1 methylation in primary refractory AML was significantly higher than that noted in chemosensitive AML (P = 0.018). Together, these results indicate that RLGS-M can be used to find novel epigenetic alterations in human cancer that are undetectable by standard methods. In addition, these results underline the potential importance of WIT-1 methylation in chemoresistant AML.

Original languageEnglish (US)
Pages (from-to)3159-3165
Number of pages7
JournalOncogene
Volume18
Issue number20
DOIs
StatePublished - May 20 1999
Externally publishedYes

Keywords

  • Acute myeloid leukemia
  • DNA methylation
  • RLGS
  • WIT-1

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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  • Cite this

    Plass, C., Yu, F., Yu, L., Strout, M. P., El-Rifai, W., Elonen, E., Knuutila, S., Marcucci, G., Young, D. C., Held, W. A., Bloomfield, C. D., & Caligiuri, M. A. (1999). Restriction landmark genome scanning for aberrant methylation in primary refractory and relapsed acute myeloid leukemia involvement of the WIT-1 gene. Oncogene, 18(20), 3159-3165. https://doi.org/10.1038/sj.onc.1202651