Molecular characterization of AML with ins(21;8)(q22;q22q22) reveals similarity to t(8;21) AML.
In acute myeloid leukemia (AML), nonrandom clonal chromosome aberrations are detectable in ∼ 55% of adult cases. Translocation t(8;21)(q22;q22) resulting in the 5'RUNX1/3'RUNX1T1 fusion gene occurs in ∼ 8% of AML cases. Also, ins(8;21) and ins(21;8) have been described that show a broad heterogeneity at the molecular level with inserted fragment sizes ranging from 2.4 to 44 Mb. Microarray-based comparative genomic hybridization (arrayCGH) in 49 intermediate-risk AML and RT-PCR-based screening in 532 AML cases allowed the detection of ins(21;8)/ins(8;21) in three cases; arrayCGH and subsequent RT-PCR revealed an ∼ 0.5 Mb sized inserted fragment generating the 5'RUNX1/3'RUNX1T1 fusion gene in one case with a submicroscopic ins(21;8)(q22;q22q22) whereas the other two cases were identified by banding analysis and RT-PCR, respectively. Gene expression profiling (GEP) and a detailed review of the literature highlighted similar biological features of AML cases with ins(21;8)/ins(8;21) and t(8;21)(q22;q22). Our study demonstrates the potential of high-resolution array-based analysis and GEP and provides further evidence that AML with insertions generating the 5'RUNX1/3'RUNX1T1 fusion not only biologically resemble the t(8;21)(q22;q22) AML subgroup, but might also share its prognostically favorable clinical behavior. Thus, similar treatment options should be considered in these patients.
Rücker
Frank G
FG
Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany.
Bullinger
Lars
L
Gribov
Alexander
A
Sill
Martin
M
Schlenk
Richard F
RF
Lichter
Peter
P
Döhner
Hartmut
H
Döhner
Konstanze
K
D000328:Adult; D056905:Chromosome Breakpoints; D002891:Chromosomes, Human, Pair 21; D002898:Chromosomes, Human, Pair 8; D016000:Cluster Analysis; D055028:Comparative Genomic Hybridization; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics; D030541:Databases, Genetic; D005260:Female; D020869:Gene Expression Profiling; D005821:Genetic Techniques; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D000075142:RUNX1 Translocation Partner 1 Protein; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics; D014178:Translocation, Genetic
D050676:Core Binding Factor Alpha 2 Subunit; D015514:Oncogene Proteins, Fusion; D011518:Proto-Oncogene Proteins; D000075142:RUNX1 Translocation Partner 1 Protein; C493728:RUNX1 protein, human; C082222:RUNX1T1 protein, human; D014157:Transcription Factors