TY - JOUR
T1 - GATA2 zinc finger 2 mutation found in acute myeloid leukemia impairs myeloid differentiation
AU - Niimi, Keiko
AU - Kiyoi, Hitoshi
AU - Ishikawa, Yuichi
AU - Hayakawa, Fumihiko
AU - Kurahashi, Shingo
AU - Kihara, Rika
AU - Tomita, Akihiro
AU - Naoe, Tomoki
N1 - Funding Information:
We would like to thank Ms. Manami Kira, Mirei Okamoto and Satomi Yamaji for secretarial and technical assistance. This study was supported by Grants-in-Aid from the Ministry of Health , Labor and Welfare for Cancer Research (Clinical Cancer Research H23 - 004 ) and the National Cancer Center Research and Development Fund ( 23-A-23 ), the Scientific Research Program of the Ministry of Education, Culture, Sports, Science and Technology , and the Global COE Program “Integrated Functional Molecular Medicine for Neuronal and Neoplastic Disorders” Japan .
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
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U2 - 10.1016/j.lrr.2013.02.002
DO - 10.1016/j.lrr.2013.02.002
M3 - Article
AN - SCOPUS:84878367249
SN - 2213-0489
VL - 2
SP - 21
EP - 25
JO - Leukemia Research Reports
JF - Leukemia Research Reports
IS - 1
ER -