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 lym phomas are due to malfunctions of the recombinatorial machinery of immunogl obulin 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 brea kpoints in primary biopsy material of fourteen t(4;11)leukemia patients wer e analysed. In all cases, duplications, deletions and inversions of less th an a few hundred nucleotides indicative of malfunctioning DNA repair mechan isms were observed. We concluded that these translocation events were initi ated by several DNA strand breaks on both participating chromosomes and sub sequent DNA repair by 'error-prone-repair' mechanisms, but not by the actio n of recombinases of the immune system.