Fusion AML1 transcript in a radiation-associated leukemia results in a truncated inhibitory AML1 protein.
AML1 is a transcription factor that is essential for normal hematopoietic development. It is the most frequent target for translocations in acute leukemia. Recently, fluorescence in situ hybridization was used to identify a novel syndrome of radiation-associated secondary acute myelogenous leukemia that had AML1 translocations. Using polymerase chain reaction, the AML1 fusion transcript was isolated from the patient who had a t(19;21) radiation-associated leukemia. The AML1 gene is fused out of frame to chromosome 19 sequences, resulting in a truncated AML protein bearing the DNA binding domain but not the transcriptional activation domain. This fusion AML1 protein functions as an inhibitor of the normal AML1 protein. (Blood. 2001;97:2168-2170)
Indiana University Cancer Center, Indianapolis, Indiana 46202, USA.
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R
Hromas
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T
Busse
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A
Carroll
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D
Mack
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Shopnick
D E
DE
Zhang
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H
Nakshatri
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K
Richkind
D000208:Acute Disease; D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics / Q000648:ultrastructure*; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics / Q000648:ultrastructure*; D050676:Core Binding Factor Alpha 2 Subunit; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D017403:In Situ Hybridization; D007951:Leukemia, Myeloid / Q000209:etiology / Q000235:genetics*; D007953:Leukemia, Radiation-Induced / Q000235:genetics*; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics* / Q000494:pharmacology; D017384:Sequence Deletion; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics*; D015533:Transcriptional Activation / Q000235:genetics*; D014178:Translocation, Genetic / Q000235:genetics*
C424128:AML1-AMP19 fusion protein, human; D050676:Core Binding Factor Alpha 2 Subunit; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D011518:Proto-Oncogene Proteins; C493728:RUNX1 protein, human; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors