A novel syndrome of radiation-associated acute myeloid leukemia involving AML1 gene translocations.
AML1 is a transcriptional activator that is essential for normal hematopoietic development. It is the most frequent target for translocations in acute leukemia. We recently identified 3 patients in whom pancytopenia developed almost 50 years after high-level radiation exposure from nuclear explosions during or after World War II. In all 3 patients, acute myeloid leukemia (AML) eventually developed that had similar characteristics and clinical courses. Cytogenetics from the 3 patients revealed a t(1;21)(p36;q22), a t(18;21)(q21;q22), and a t(19;21)(q13.4;q22). By fluorescent in situ hybridization (FISH), all 3 translocations disrupted the AML1 gene. Two of these AML1 translocations, the t(18;21) and the t(19;21), have not been reported previously. It is possible that the AML1 gene is a target for radiation-induced AML. (Blood. 2000;95:4011-4013)
Hromas
R
R
Indiana University Cancer Center, Indianapolis, IN 46202, USA. rhromas@iupui.edu
Shopnick
R
R
Jumean
H G
HG
Bowers
C
C
Varella-Garcia
M
M
Richkind
K
K
D000208:Acute Disease; D000368:Aged; D001853:Bone Marrow / Q000473:pathology; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D002887:Chromosomes, Human, Pair 18; D002888:Chromosomes, Human, Pair 19; D002891:Chromosomes, Human, Pair 21; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins / Q000235:genetics*; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000473:pathology; D007953:Leukemia, Radiation-Induced / Q000235:genetics* / Q000473:pathology; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics; D009689:Nuclear Warfare; D011518:Proto-Oncogene Proteins; D011847:Radioactive Fallout; D013577:Syndrome; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic
D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; C493728:RUNX1 protein, human; D011847:Radioactive Fallout; D014157:Transcription Factors