The silent mutational landscape of infant MLL-AF4 pro-B acute lymphoblastic leukemia

Genes Chromosomes Cancer. 2013 Oct;52(10):954-60. doi: 10.1002/gcc.22090. Epub 2013 Jul 26.

Abstract

Over 90% of infants (< 1-year-old) diagnosed with leukemia have pro-B acute lymphoblastic leukemia (ALL) containing the MLL-AF4 fusion. When compared with other forms of paediatric ALL affecting later B-cell differentiation, MLL-AF4 pro-B is associated with a dismal prognosis with a typical 5-year disease-free survival of <20%. MLL-AF4 may be sufficient on its own for leukemogenesis or the gene-fusion product may alternatively predispose transformed cells to global genetic instability, enhancing the acquisition of additional key mutations. To gain insight into the genomic landscape of infant MLL-AF4 pro-B ALL we performed whole genome sequencing of diagnostic leukemic blasts and matched germline samples from three MLL-AF4 pro-B ALL infants. Our analysis revealed few somatic changes (copy number abnormalities, loss of heterozygosity, or single nucleotide variants), demonstrating that only a very small number of mutations are necessary to generate infant MLL-leukemia.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA Copy Number Variations
  • DNA Mutational Analysis
  • Genome, Human
  • Genomics
  • Humans
  • INDEL Mutation / genetics
  • Infant
  • Infant, Newborn
  • Loss of Heterozygosity
  • Myeloid-Lymphoid Leukemia Protein / genetics*
  • Oncogene Proteins, Fusion / genetics*
  • Polymorphism, Single Nucleotide
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Sequence Analysis, DNA
  • Translocation, Genetic

Substances

  • MLL-AF4 fusion protein, human
  • Oncogene Proteins, Fusion
  • Myeloid-Lymphoid Leukemia Protein