RUNX3 promoter hypermethylation is frequent in leukaemia cell lines and associated with acute myeloid leukaemia inv(16) subtype

Marcos R.H. Estécio, Sirisha Maddipoti, Carlos Bueso-Ramos, Courtney D. Dinardo, Hui Yang, Yue Wei, Kimie Kondo, Zhihong Fang, William Stevenson, Kun Sang Chang, Sherry A. Pierce, Zachary Bohannan, Gautam Borthakur, Hagop Kantarjian, Guillermo Garcia-Manero

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Correlative and functional studies support the involvement of the RUNX gene family in haematological malignancies. To elucidate the role of epigenetics in RUNX inactivation, we evaluated promoter DNA methylation of RUNX1, 2, and 3 in 23 leukaemia cell lines and samples from acute myeloid leukaemia (AML), acute lymphocytic leukaemia (ALL) and myelodysplatic syndromes (MDS) patients. RUNX1 and RUNX2 gene promoters were mostly unmethylated in cell lines and clinical samples. Hypermethylation of RUNX3 was frequent among cell lines (74%) and highly variable among patient samples, with clear association to cytogenetic status. High frequency of RUNX3 hypermethylation (85% of the 20 studied cases) was found in AML patients with inv(16)(p13.1q22) compared to other AML subtypes (31% of the other 49 cases). RUNX3 hypermethylation was also frequent in ALL (100% of the six cases) but low in MDS (21%). In support of a functional role, hypermethylation of RUNX3 was correlated with low levels of protein, and treatment of cell lines with the DNA demethylating agent, decitabine, resulted in mRNA re-expression. Furthermore, relapse-free survival of non-inv(16)(p13.1q22) AML patients without RUNX3 methylation was significantly better (P = 0·016) than that of methylated cases. These results suggest that RUNX3 silencing is an important event in inv(16)(p13.1q22) leukaemias.

Original languageEnglish (US)
Pages (from-to)344-351
Number of pages8
JournalBritish Journal of Haematology
Volume169
Issue number3
DOIs
StatePublished - May 1 2015

Keywords

  • Acute myeloid leukaemia
  • DNA methylation
  • Gene expression
  • Inv(16)(p13.1q22)
  • RUNX3

ASJC Scopus subject areas

  • Hematology

MD Anderson CCSG core facilities

  • Tissue Biospecimen and Pathology Resource

Fingerprint

Dive into the research topics of 'RUNX3 promoter hypermethylation is frequent in leukaemia cell lines and associated with acute myeloid leukaemia inv(16) subtype'. Together they form a unique fingerprint.

Cite this