ASXL1 exon 12 mutations are frequent in AML with intermediate risk karyotype and are independently associated with an adverse outcome
S Schnittger, C Eder, S Jeromin, T Alpermann, A Fasan… - Leukemia, 2013 - nature.com
S Schnittger, C Eder, S Jeromin, T Alpermann, A Fasan, V Grossmann, A Kohlmann, T Illig…
Leukemia, 2013•nature.comWe aimed at evaluating ASXL1mut in 740 AML with intermediate risk karyotype for
frequency, association with other mutations and impact on outcome. Five hundred fifty-three
cases had a normal karyotype (NK) and 187 had intermediate risk aberrant cytogenetics.
Overall, ASXL1mut were detected in 127/740 patients (17.2%). ASXL1mut were more
frequent in males than in females (23.5% vs 9.9%, P< 0.001). They were associated with
higher age (median: 71.8 vs 61.8, P< 0.001), a history of preceding myelodysplastic …
frequency, association with other mutations and impact on outcome. Five hundred fifty-three
cases had a normal karyotype (NK) and 187 had intermediate risk aberrant cytogenetics.
Overall, ASXL1mut were detected in 127/740 patients (17.2%). ASXL1mut were more
frequent in males than in females (23.5% vs 9.9%, P< 0.001). They were associated with
higher age (median: 71.8 vs 61.8, P< 0.001), a history of preceding myelodysplastic …
Abstract
We aimed at evaluating ASXL1mut in 740 AML with intermediate risk karyotype for frequency, association with other mutations and impact on outcome. Five hundred fifty-three cases had a normal karyotype (NK) and 187 had intermediate risk aberrant cytogenetics. Overall, ASXL1mut were detected in 127/740 patients (17.2%). ASXL1mut were more frequent in males than in females (23.5% vs 9.9%, P< 0.001). They were associated with higher age (median: 71.8 vs 61.8, P< 0.001), a history of preceding myelodysplastic syndromes, and with a more immature immunophenotype compared with patients with wild-type ASXL1 (ASXL1wt). ASXL1mut were more frequent in patients with aberrant karyotype (58/187; 31.0%), especially in cases with trisomy 8 (39/74; 52.7%), than in those with NK (69/553; 12.5%; P< 0.001). ASXL1mut were observed more frequent in RUNX1mut (P< 0.001), and less frequent in NPM1mut (P< 0.001), FLT3-internal tandem duplication (ITD)(P< 0.001), FLT3-TKD (P= 0.001) and DNMT3Amut (P< 0.001). Patients with ASXL1mut had a shorter overall survival (OS)(P< 0.001) and event free survival (P= 0.012) compared with ASXL1wt. In multivariable analysis, ASXL1mut was an independent adverse factor for OS (P= 0.032, relative risk: 1.70). In conclusion, ASXL1mut belong to the most frequent mutations in intermediate risk group AML. Their strong and independent dismal prognostic impact suggests the inclusion into the diagnostic work-up of AML.
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