Simple variant t(8;21) acute myeloid leukemias harbor insertions of the AML1 or ETO genes.
We report on the molecular characterization of two acute myeloid leukemias (AML), one AML-M1 (patient 1) and one AML-M2 (patient 2) with t(8;21)(p21;q22) and t(8;20)(q22;p13), respectively, at diagnosis. The locations of the breakpoints, 21q22 in patient 1 and 8q22 in patient 2, prompted us to search for a cryptic t(8;21)(q22;q22) and involvement of the AML1 and ETO genes. Dual-color fluorescence in situ hybridization (FISH) using whole chromosome painting probes for chromosomes 8, 20, and 21 confirmed the conventional cytogenetic karyotypes. However, dual-color FISH using appropriate ETO and AML1 probes disclosed an insertion of AML1 into 8q22 on the derivative chromosome 8 in patient 1 and of ETO into 21q22 on one chromosome 21 in patient 2, leading to AML1-ETO fusion signals. Both cases expressed an AML1-ETO transcript, shown by reverse transcriptase polymerase chain reaction and cDNA sequencing. Creation of functional AML1-ETO fusion genes in these two simple variant t(8;21) probably occurred through complex mechanisms, combining translocation and insertion of chromosomal segments.
Taviaux
S
S
CNRS-IGH, Montpellier, France.
Brunel
V
V
Dupont
M
M
Fernandez
F
F
Ferraz
C
C
Carbuccia
N
N
Sainty
D
D
Demaille
J
J
Birg
F
F
Lafage-Pochitaloff
M
M
D000293:Adolescent; D000328:Adult; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D050676:Core Binding Factor Alpha 2 Subunit; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D015514:Oncogene Proteins, Fusion; D000075142:RUNX1 Translocation Partner 1 Protein; D011993:Recombinant Fusion Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic / Q000235:genetics*
C107844:AML1-ETO fusion protein, human; D050676:Core Binding Factor Alpha 2 Subunit; D015514:Oncogene Proteins, Fusion; D000075142:RUNX1 Translocation Partner 1 Protein; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors