Regarding the clinical outcome of these patients, cohesin-mutated patients showed a shorter
overall survival (3.1vs.5.2 years, p=0.052) and a shorter time to sAML progression (1.4vs.8.3
years, p<0.0001).
To further study the negative impact of these mutations, analyses were carried out for each
IPSS-R groups, separately. Interestingly, in very low/low/intermediate IPSS-R patients, these
analyses showed that cohesin mutations were the sole factor significantly associated with an
earlier progression to sAML (p<0.001), together with blasts in bone marrow. In addition, in
the multivariate analysis, the presence of cohesin mutations was associated with an earlier
progression to sAML (HR=2.438 (95%CI, 1.193-4.963); p=0.015).
Conclusions: Mutations in cohesin complex genes (mainly STAG2) are associated with a worse
prognosis due to a higher rate of AML evolution and a shorter time to progression to AML in
the global cohort. Of note, mutations in the cohesin-complex were associated with a potential
prognostic impact in very low/low/intermediate IPSS-R subgroups. Therefore, analysis of
these mutations, especially in this subgroup of patients, should be carried out.