The silent mutational landscape of infant MLL-AF4 pro-B acute lymphoblastic leukemia
A partir d'échantillons prélevés sur des patients pédiatriques atteints d'une leucémie lymphoblastique aiguë pro-B présentant une fusion des gènes MLL-AF4, cette étude de séquençage du génome entier montre que la maladie est associée à un très petit nombre de mutations somatiques
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. © 2013 Wiley Periodicals, Inc.