Transcription factor GATA-2 gene is located near 3q21 breakpoints in myeloid leukemia.
Rearrangements affecting chromosome band 3q21 are observed in a subgroup of patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). However, little is known about the molecular consequences of such aberrations. We therefore established a PAC contig in the 3q21 breakpoint region and identified potential protein coding sequences by exon trapping. One of the exons isolated was from the human GATA-2 gene, which we showed to be transcribed from telomere to centromere. The majority of 3q21 breakpoints are located telomeric to the transcribed portion of this gene in a region that in mice appears to be necessary for proper promoter function. Results of GATA-2 expression analyses in leukemic cell lines as well as primary patient samples are compatible with the hypothesis that 3q21 aberrations contribute to leukemogenesis through deregulation of the hematopoietic transcription factor GATA-2.
Wieser
R
R
Institut für Medizinische Biologie der Universität Wien, Währingerstrasse 10, Vienna, A-1090, Austria.
Volz
A
A
Vinatzer
U
U
Gardiner
K
K
Jäger
U
U
Mitterbauer
M
M
Ziegler
A
A
Fonatsch
C
C
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000818:Animals; D002503:Centromere / Q000235:genetics; D019457:Chromosome Breakage / Q000235:genetics*; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D020451:Contig Mapping; D004268:DNA-Binding Proteins / Q000235:genetics*; D005091:Exons / Q000235:genetics; D050989:GATA2 Transcription Factor; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007951:Leukemia, Myeloid / Q000235:genetics*; D051379:Mice; D008875:Middle Aged; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D016615:Telomere / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics; D014178:Translocation, Genetic / Q000235:genetics; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D050989:GATA2 Transcription Factor; C494711:GATA2 protein, human; C494712:Gata2 protein, mouse; D012333:RNA, Messenger; D014157:Transcription Factors