Highly variable mutational profile of ASXL 1 in myelofibrosis

Objective Somatic mutations in ASXL 1 seem to have a negative prognostic impact in patients with several myeloid neoplasms, including myelofibrosis ( MF ). The aim of this work was to determine the prevalence and profile of ASXL 1 mutations in MF . Methods We analyzed mutations in ASXL 1 in 70 consecutive MF patients from 8 S panish hospitals by means of S anger sequencing, as well as JAK 2 , CALR , and MPL mutations. Results ASXL 1 mutations were found in 16/70 (23%) of cases, most commonly p.Gly646TrpfsX12 (5/16). Most mutations (13/16) were frameshift mutations. Of 54 ASXL 1 ‐ wild‐type patients, 32 (59%) had at least one single nucleotide polymorphism ( SNP ), 27 of them had g.78128 C > T , g.79017 A > C , and g.79085 T > C [triple SNP ( TSNP ) patients]. The 5‐yr overall survival probability of TSNP patients was 67% (95% CI , 43–91%) vs. 90% (95% CI , 77–100%) in ASXL 1 ‐ WT patients ( P = 0.152). Conclusion ASXL 1 mutations were found in 23% of cases, p.Gly646TrpfsX12 being the most frequent. About 85% of mutations were found only in individual cases and 46% had not previously been reported, a pattern also seen in other series. Fifty percent of ASXL 1 ‐ WT patients had a combination of three specific SNP s that might have a prognostic correlation that needs to be determined in larger series.