A DNA damage repair mechanism is involved in the origin of chromosomal translocations t(4;11) in primary leukemic cells.
Some chromosomal translocations involved in the origin of leukemias and lymphomas are due to malfunctions of the recombinatorial machinery of immunoglobulin and T-cell receptor-genes. This mechanism has also been proposed for translocations t(4;11)(q21;q23), which are regularly associated with acute pro-B cell leukemias in early childhood. Here, reciprocal chromosomal breakpoints in primary biopsy material of fourteen t(4;11)-leukemia patients were analysed. In all cases, duplications, deletions and inversions of less than a few hundred nucleotides indicative of malfunctioning DNA repair mechanisms were observed. We concluded that these translocation events were initiated by several DNA strand breaks on both participating chromosomes and subsequent DNA repair by 'error-prone-repair' mechanisms, but not by the action of recombinases of the immune system.
Gillert
E
E
Chair of Genetics, University of Erlangen-Nürnberg, Staudtstr. 5, D-91058 Erlangen, Germany.
Leis
T
T
Repp
R
R
Reichel
M
M
Hösch
A
A
Breitenlohner
I
I
Angermüller
S
S
Borkhardt
A
A
Harbott
J
J
Lampert
F
F
Griesinger
F
F
Greil
J
J
Fey
G H
GH
Marschalek
R
R
D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002051:Burkitt Lymphoma / Q000209:etiology / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002880:Chromosomes, Human, Pair 11; D002894:Chromosomes, Human, Pair 4; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007223:Infant; D015448:Leukemia, B-Cell / Q000209:etiology / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D051788:Myeloid-Lymphoid Leukemia Protein; D009687:Nuclear Proteins / Q000235:genetics; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000209:etiology / Q000235:genetics; D011519:Proto-Oncogenes; D014157:Transcription Factors; D035602:Transcriptional Elongation Factors; D014178:Translocation, Genetic
D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; D009687:Nuclear Proteins; D014157:Transcription Factors; D035602:Transcriptional Elongation Factors; D051788:Myeloid-Lymphoid Leukemia Protein; C081449:AFF1 protein, human; D011495:Histone-Lysine N-Methyltransferase