Cooperating gene mutations in childhood acute myeloid leukemia with special reference on mutations of ASXL1, TET2, IDH1, IDH2 and DNMT3A
Menée sur des échantillons sanguins prélevés sur 206 patients pédiatriques atteints d'une leucémie myéloïde aiguë, cette étude analyse la distribution de mutations de 19 gènes impliqués dans la régulation épigénétique
Genes involving epigenetic regulators have recently been described in adult AML. Similar studies are limited in children. We analyzed gene mutations and cooperation in pediatric AML with special reference on mutated epigenetic regulators. Nineteen gene mutations including 8 class I genes, 4 class II genes, WT1 and TP53 (class III), and 5 epigenetic regulator genes (class IV), were analyzed in 206 children with de novo AML. Mutational analysis was performed with PCR-based assay followed by direct sequencing. One hundred seventeen of 206 patients (56.8%) had at least one mutation: 51% class I, 13% class II, 6.8% class III and 5.6% class IV. FLT3-ITD was most frequent, 29% of patients had more than one gene mutation. Two patients carried ASXL1 mutations, both with t(8;21), 2 had DNMT3A mutations, 2 had IDH1 mutations, 1 had IDH2 mutation and 3 had TET2 mutations. Both patients with IDH1 mutations had AML-M0 subtype and MLL-PTD. Cooperating mutations with mutated epigenetic regulators were observed in 8 of 10 patients. We conclude that mutated epigenetic regulators were much less than those in adult AML but with frequent cooperating mutations. ASXL1, TET2 and IDH1 mutations were associated with specific genetic subtypes.
Blood 2013