Frequent ASXL2 mutations in acute myeloid leukemia patients with t(8;21)/RUNX1-RUNX1T1 chromosomal translocations
A partir d'échantillons prélevés sur 110 patients atteints d'une leucémie myéloïde aiguë présentant une translocation t(8;21), cette étude française identifie la présence fréquente de mutations somatiques du gène ASXL2 et évalue l'association entre la présence de mutations des gènes ASXL1 ou ASXL2 et le risque de récidive
Acute myeloid leukemia (AML) with t(8;21)(q22;q22) is considered to have favorable risk however nearly half of t(8;21) patients are not cured and recent studies have highlighted remarkable genetic heterogeneity in this subset of AML. Here we identify somatic mutations in Additional Sex Combs-like 2 (ASXL2) in 22.7% (25/110) of patients with t(8;21) but not in inv(16)/t(16;16) (0/60) or RUNX1-mutated AML (0/26). ASXL2 mutations were similarly frequent in adult and pediatric t(8;21) and mutually exclusive with ASXL1 mutations. Although overall survival was similar between ASXL1 or ASXL2 mutant t(8;21) AML patients and wildtype counterparts, patients with ASXL1 or ASXL2 mutations had a cumulative incidence of relapse of 54.6% and 36.0%, respectively, compared with 25% in ASXL1/2 wildtype counterparts (p=0.226). These results identify a high-frequency mutation in t(8;21) AML and identify the need for future studies to investigate the clinical and biological relevance of ASXL2 mutations in this unique subset of AML.