Document Detail

Frequent mutations in the GATA-1 gene in the transient myeloproliferative disorder of Down syndrome.
MedLine Citation:
PMID:  12816863     Owner:  NLM     Status:  MEDLINE    
Transient myeloproliferative disorder (TMD) is a leukemoid reaction occurring occasionally in Down syndrome newborn infants. Acute megakaryocytic leukemia (AMKL) develops in approximately 20% to 30% of the cases with TMD. Recently, acquired mutations in the N-terminal activation domain of the GATA-1 gene, encoding the erythroid/megakaryocytic transcription factor GATA-1, have been reported in Down syndrome-related AMKL (DS-AMKL). To understand the multistep leukemogenesis in Down syndrome, GATA-1 mutations were investigated in patients with TMD. We show here that mutations in the GATA-1 gene were detected in 21 of 22 cases with TMD. Most of the mutations in TMD were located in the regions including exon 2 and were essentially identical to those observed in DS-AMKL. In the DS-AMKL cell line, MGS, which itself expresses only a truncated mutant of GATA-1, expression of full-length GATA-1 induced the differentiation toward the erythroid lineage. However, expression of the short form of GATA-1 did not induce erythroid differentiation. These results indicate that expression of GATA-1 with a defective N-terminal activation domain contributes to the expansion of TMD blast cells and that other genetic changes contribute to the development of AMKL in Down syndrome.
Gang Xu; Masumi Nagano; Rika Kanezaki; Tsutomu Toki; Yasuhide Hayashi; Takeshi Taketani; Tomohiko Taki; Tetsuo Mitui; Kenichi Koike; Koji Kato; Masue Imaizumi; Isao Sekine; Yasuhiko Ikeda; Ryoji Hanada; Masahiro Sako; Kazuko Kudo; Seiji Kojima; Osamu Ohneda; Masayuki Yamamoto; Etsuro Ito
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2003-06-19
Journal Detail:
Title:  Blood     Volume:  102     ISSN:  0006-4971     ISO Abbreviation:  Blood     Publication Date:  2003 Oct 
Date Detail:
Created Date:  2003-10-06     Completed Date:  2003-11-24     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2960-8     Citation Subset:  AIM; IM    
Department of Pediatrics, Hirosaki University School of Medicine, Hirosaki, Aomori, 036-8563 Japan.
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MeSH Terms
Age Factors
Cell Differentiation
Cell Line
Cell Lineage
DNA, Complementary / metabolism
DNA-Binding Proteins / genetics*
Down Syndrome / complications,  genetics*
Erythroid-Specific DNA-Binding Factors
Flow Cytometry
GATA1 Transcription Factor
Genetic Vectors
Infant, Newborn
K562 Cells
Leukemia, Megakaryoblastic, Acute / genetics
Models, Genetic
Myeloproliferative Disorders / genetics*
Protein Structure, Tertiary
Retroviridae / genetics
Reverse Transcriptase Polymerase Chain Reaction
Sequence Analysis, DNA
Transcription Factors / genetics*
Reg. No./Substance:
0/DNA, Complementary; 0/DNA-Binding Proteins; 0/Erythroid-Specific DNA-Binding Factors; 0/GATA1 Transcription Factor; 0/GATA1 protein, human; 0/Transcription Factors

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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