Molecular characterization of a rare MLL-AF4 (MLL-AFF1) fusion rearrangement in infant leukemia

Cancer Genet Cytogenet. 2007 Oct 1;178(1):61-4. doi: 10.1016/j.cancergencyto.2007.05.023.

Abstract

The t(4;11)(q21;q23) involving the genes MLL and AF4 (alias for AFF1) is detected in 50-70% of infant leukemia. We characterize at both the DNA and RNA level a rare MLL-AF4 fusion transcript identified in a 15-month-old girl with acute lymphoblastic leukemia. Direct sequence analysis of the reverse transcriptase-polymerase chain reaction product showed an in-frame fusion between MLL exon 9 and AF4 exon 6. We further demonstrated that the genomic breakpoints were located 1,553 bp downstream of MLL exon 9 and 1,239 bp upstream of AF4 exon 6. Four Alu repeats were detected in MLL intron 9 and two Alu repeats and one LINE1 repetitive element were identified downstream of AF4 exon 5. Finally, a 9-bp polypurine (A) tract and an 8-bp polypyrimidine (T) tract were found flanking the translocation breakpoint. In summary, we have characterized at both the RNA and the DNA level a rare MLL-AF4 fusion variant that was presumably mediated by Alu repeats or polypurine and polypyrimidine tracts located in the vicinity of genomic breakpoints.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • DNA / metabolism
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / physiology*
  • Exons
  • Female
  • Histone-Lysine N-Methyltransferase
  • Humans
  • Infant
  • Leukemia / genetics*
  • Molecular Sequence Data
  • Myeloid-Lymphoid Leukemia Protein / genetics*
  • Myeloid-Lymphoid Leukemia Protein / physiology*
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / physiology*
  • Oncogene Proteins, Fusion / genetics*
  • Purines / chemistry
  • Pyrimidines / chemistry
  • RNA / metabolism
  • Sequence Analysis, DNA
  • Transcriptional Elongation Factors

Substances

  • DNA-Binding Proteins
  • KMT2A protein, human
  • Nuclear Proteins
  • Oncogene Proteins, Fusion
  • Purines
  • Pyrimidines
  • Transcriptional Elongation Factors
  • Myeloid-Lymphoid Leukemia Protein
  • AFF1 protein, human
  • RNA
  • DNA
  • Histone-Lysine N-Methyltransferase