Low expression of ASH2L protein correlates with a favorable outcome in acute myeloid leukemia

Jill S. Butler, Yi Hua Qiu, Nianxiang Zhang, Suk Young Yoo, Kevin R. Coombes, Sharon Y.R. Dent, Steven M. Kornblau

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

ASH2L encodes a trithorax group protein that is a core component of all characterized mammalian histone H3K4 methyltransferase complexes, including mixed lineage leukemia (MLL) complexes. ASH2L protein levels in primary leukemia patient samples have not yet been defined. We analyzed ASH2L protein expression in 511 primary AML patient samples using reverse phase protein array (RPPA) technology. We discovered that ASH2L expression is significantly increased in a subset of patients carrying fms-related tyrosine kinase 3 (FLT3) mutations. Furthermore, we observed that low levels of ASH2L are associated with increased overall survival. We also compared ASH2L levels to the expression of 230 proteins previously analyzed on this array. ASH2L expression was inversely correlated with 32 proteins, mostly involved in cell adhesion and cell cycle inhibition, while a positive correlation was observed for 50 proteins, many of which promote cell proliferation. Together, these results indicate that a lower level of ASH2L protein is beneficial to AML patients.

Original languageEnglish (US)
Pages (from-to)1207-1218
Number of pages12
JournalLeukemia and Lymphoma
Volume58
Issue number5
DOIs
StatePublished - May 4 2017
Externally publishedYes

Keywords

  • ASH2L
  • chromatin
  • epigenetics
  • histone modifications
  • leukemia
  • methyltransferase

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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