Involvement of the AML1 gene in the t(3;21) in therapy-related leukemia and in chronic myeloid leukemia in blast crisis.
A nonrandom translocation between chromosomes 3 and 21, t(3;21)(q26.2;q22) has been detected in patients with a myelodysplastic syndrome or acute myeloid leukemia after treatment (t-MDS/t-AML) for a primary malignant disease and in chronic myelogenous leukemia in blast crisis (CML-BC). In these patients, the breakpoint on chromosome 21 is at band 21q22. This band is also involved in the t(8;21)(q22;q22) detected in 40% of the patients with acute myeloid leukemia subtype M2 (AML-M2) de novo who have an abnormal karyotype. In the t(8;21), the AML1 gene is the site of the breakpoint on chromosome 21. The AML1 gene is transcribed from telomere to centromere, and in the t(8;21) the 5' part of AML1 is fused to the ETO gene on chromosome 8 to produce the chimeric AML1/ETO on the der(8) chromosome. We found that AML1 is also rearranged in two t-AML patients and in one CML-BC patient with the t(3;21), but the breakpoints are approximately 40 to 60 kb downstream to those of AML-M2 patients. This region contains at least one additional exon of AML1, as determined by using an AML1 cDNA as a probe in Southern blot analysis. The t(3;21) breakpoints for the remaining patients could not be determined because, by fluorescence in situ hybridization analysis, the breaks are outside of the region covered by the available probes.
Nucifora
G
G
Department of Medicine, University of Chicago, IL.
Birn
D J
DJ
Espinosa
R
R
Erickson
P
P
LeBeau
M M
MM
Roulston
D
D
McKeithan
T W
TW
Drabkin
H
H
Rowley
J D
JD
D000328:Adult; D000368:Aged; D001483:Base Sequence; D001752:Blast Crisis / Q000235:genetics*; D015139:Blotting, Southern; D002871:Chromosome Banding; D002874:Chromosome Mapping; D016386:Chromosome Walking; D002891:Chromosomes, Human, Pair 21; D002893:Chromosomes, Human, Pair 3; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D006801:Humans; D007621:Karyotyping; D007938:Leukemia / Q000209:etiology / Q000235:genetics*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009190:Myelodysplastic Syndromes / Q000235:genetics; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction; D015183:Restriction Mapping; D014178:Translocation, Genetic
D004273:DNA, Neoplasm; D009838:Oligodeoxyribonucleotides