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, Wael 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

51 Citations (Scopus)

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

Fingerprint

Acute Myeloid Leukemia
Methylation
Genome
Genes
DNA Methylation
Recurrence
Bone Marrow
Nucleic Acid Regulatory Sequences
Human Chromosomes
Hematologic Neoplasms
Epigenomics
Sequence Analysis
DNA
Incidence
Neoplasms

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Restriction landmark genome scanning for aberrant methylation in primary refractory and relapsed acute myeloid leukemia involvement of the WIT-1 gene. / Plass, Christoph; Yu, Feng; Yu, Li; Strout, Matthew P.; El-Rifai, Wael; Elonen, Erkki; Knuutila, Sakari; Marcucci, Guido; Young, Donn C.; Held, William A.; Bloomfield, Clara D.; Caligiuri, Michael A.

In: Oncogene, Vol. 18, No. 20, 20.05.1999, p. 3159-3165.

Research output: Contribution to journalArticle

Plass, C, Yu, F, Yu, L, Strout, MP, El-Rifai, W, Elonen, E, Knuutila, S, Marcucci, G, Young, DC, Held, WA, Bloomfield, CD & Caligiuri, MA 1999, 'Restriction landmark genome scanning for aberrant methylation in primary refractory and relapsed acute myeloid leukemia involvement of the WIT-1 gene', Oncogene, vol. 18, no. 20, pp. 3159-3165. https://doi.org/10.1038/sj.onc.1202651
Plass, Christoph ; Yu, Feng ; Yu, Li ; Strout, Matthew P. ; El-Rifai, Wael ; Elonen, Erkki ; Knuutila, Sakari ; Marcucci, Guido ; Young, Donn C. ; Held, William A. ; Bloomfield, Clara D. ; Caligiuri, Michael A. / Restriction landmark genome scanning for aberrant methylation in primary refractory and relapsed acute myeloid leukemia involvement of the WIT-1 gene. In: Oncogene. 1999 ; Vol. 18, No. 20. pp. 3159-3165.
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