Plant homeodomain finger protein 2 as a novel IKAROS target in acute lymphoblastic leukemia

Epigenomics. 2018 Jan;10(1):59-69. doi: 10.2217/epi-2017-0092. Epub 2017 Oct 10.

Abstract

Aim: Clinical significance of plant homeodomain finger 2 (PHF2) expressions is explored in acute lymphoblastic leukemia (ALL) patients.

Methods: mRNA level was examined by qPCR. The retroviral gene expression, shRNA knockdown and chromatin-immunoprecipitation are used to observe IKAROS regulation on PHF2 transcription.

Results: PHF2 expression is significantly reduced in subsets of ALL patients, and PHF2 low expression correlates with leukemia cell proliferation and an elevation of several poor prognostic markers in B-cell ALL. IKAROS directly promotes PHF2 expression and patients with IKAROS deletion have significantly lower PHF2 expression. Casein kinase II (CK2) inhibitor significantly promotes PHF2 expression in an IKAROS-dependent manner, and casein kinase II inhibitor treatment also results in an increase of PHF2 expression and enrichment of IKAROS and H3K4me3 at PHF2 promoter in primary cells.

Conclusion: Our results demonstrate that the IKAROS promotes PHF2 expression, and suggest that PHF2 low expression works with the IKAROS gene deletion to drive oncogenesis of ALL.

Keywords: IKZF1; PHF2; acute lymphoblastic leukemia; histone modification.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Bone Marrow / metabolism
  • Cell Line
  • Cell Proliferation
  • Child
  • Female
  • Homeodomain Proteins / genetics*
  • Humans
  • Ikaros Transcription Factor / genetics*
  • Male
  • Middle Aged
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Prognosis
  • RNA, Messenger / genetics
  • RNA, Small Interfering / genetics
  • Young Adult

Substances

  • Homeodomain Proteins
  • IKZF1 protein, human
  • PHF2 protein, human
  • RNA, Messenger
  • RNA, Small Interfering
  • Ikaros Transcription Factor