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

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

Author information

1
Molecular and Population Genetics, Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey, SM2 5NG, UK.

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.

PMID:
23893660
DOI:
10.1002/gcc.22090
[Indexed for MEDLINE]

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