A DNA damage repair mechanism is involved in the origin of chromosomal translocations t(4;11) in primary leukemic cells

Oncogene. 1999 Aug 19;18(33):4663-71. doi: 10.1038/sj.onc.1202842.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Base Sequence
  • Burkitt Lymphoma / etiology
  • Burkitt Lymphoma / genetics
  • Child
  • Child, Preschool
  • Chromosomes, Human, Pair 11
  • Chromosomes, Human, Pair 4
  • DNA Damage*
  • DNA Repair*
  • DNA-Binding Proteins / genetics
  • Female
  • Histone-Lysine N-Methyltransferase
  • Humans
  • Infant
  • Leukemia, B-Cell / etiology
  • Leukemia, B-Cell / genetics*
  • Male
  • Molecular Sequence Data
  • Myeloid-Lymphoid Leukemia Protein
  • Nuclear Proteins / genetics
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / etiology
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Proto-Oncogenes*
  • Transcription Factors*
  • Transcriptional Elongation Factors
  • Translocation, Genetic*

Substances

  • DNA-Binding Proteins
  • KMT2A protein, human
  • Nuclear Proteins
  • Transcription Factors
  • Transcriptional Elongation Factors
  • Myeloid-Lymphoid Leukemia Protein
  • AFF1 protein, human
  • Histone-Lysine N-Methyltransferase

Associated data

  • GENBANK/AJ235330
  • GENBANK/AJ235331
  • GENBANK/AJ235332
  • GENBANK/AJ235333
  • GENBANK/AJ235334
  • GENBANK/AJ235335
  • GENBANK/AJ235336
  • GENBANK/AJ235337
  • GENBANK/AJ235338
  • GENBANK/AJ235339
  • GENBANK/AJ235340
  • GENBANK/AJ235341
  • GENBANK/AJ235342
  • GENBANK/AJ235343
  • GENBANK/AJ235344
  • GENBANK/AJ235345
  • GENBANK/AJ235346
  • GENBANK/AJ235347
  • GENBANK/AJ235348
  • GENBANK/AJ235349
  • GENBANK/AJ235350
  • GENBANK/AJ235351
  • GENBANK/AJ235352
  • GENBANK/AJ235353
  • GENBANK/AJ235354
  • GENBANK/AJ235355
  • GENBANK/AJ235356
  • GENBANK/AJ235357
  • GENBANK/AJ235358
  • GENBANK/AJ235359