GATA2 zinc finger 2 mutation found in acute myeloid leukemia impairs myeloid differentiation

Keiko Niimi; Hitoshi Kiyoi; Yuichi Ishikawa; Fumihiko Hayakawa; Shingo Kurahashi; Rika Kihara; Akihiro Tomita; Tomoki Naoe

doi:10.1016/j.lrr.2013.02.002

GATA2 zinc finger 2 mutation found in acute myeloid leukemia impairs myeloid differentiation

Leuk Res Rep. 2013 Mar 19;2(1):21-5. doi: 10.1016/j.lrr.2013.02.002. eCollection 2013.

Authors

Keiko Niimi¹, Hitoshi Kiyoi¹, Yuichi Ishikawa¹, Fumihiko Hayakawa¹, Shingo Kurahashi¹, Rika Kihara¹, Akihiro Tomita¹, Tomoki Naoe¹

Affiliation

¹ Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.

Abstract

We identified two novel GATA2 mutations in acute myeloid leukemia (AML). One mutation (p.R308P-GATA2) was a R308P substitution within the zinc finger (ZF)-1 domain, and the other (p.A350_N351ins8-GATA2) was an eight-amino-acid insertion between A350 and N351 residues within the ZF-2 domain. p.R308P-GATA2 did not affect DNA-binding and transcriptional activities, while p.A350_N351ins8-GATA2 reduced them, and impaired G-CSF-induced granulocytic differentiation of 32D cells. Although p.A350_N351ins8-GATA2 did not show a dominant-negative effect over wild-type (Wt)-GATA2 by the reporter assay, it might be involved in the pathophysiology of AML by impairing myeloid differentiation because of little Wt-GATA2 expression in primary AML cells harboring the p.A350_N351ins8 mutation.

Keywords: AML; Differentiation; GATA2; Mutation.