It is now well established that approximately 90% of patients with primary myelofibrosis (PMF) express one of three “driver” mutations ( JAK2 , CALR , and MPL ) that are often mutually exclusive and shown to be phenotypically and prognostically relevant [ 1 ]. In addition, targeted sequencing has revealed other mutations or DNA variants in more than 80% of patients with PMF, the most frequent being ASXL1 (36%), TET2 (18%), SRSF2 (18%), and U2AF1 (16%) [ 2 ]. ASXL1 and SRSF2 mutations have consistently been shown to be prognostically detrimental in PMF [ 1 ], while other mutations, such as SF3B1 and U2AF1 , were phenotypically characterized by ring sideroblasts [ 3 ] and anemia/thrombocytopenia [ 4 ], respectively. The unique association between U2AF1 mutations and anemia and/or thrombocytopenia has also been demonstrated in myelodysplastic syndromes (MDS) [ 5 ]. In both PMF and MDS, U2AF1 mutations were associated with inferior survival, which, however, might have been accounted for by their association with other previously recognized risk factors, including anemia and thrombocytopenia [ 4 , 6 , 7 ]. In the current study, we classified U2AF1 mutations in PMF into the two main mutation variants, Q157 and S34, in order to examine differences in phenotype and prognostic relevance. The rationale for grouping U2AF1 mutations into these two mutation variants include (i) almost all PMF patients harbor one of these two mutations, (ii) classification in the two specific U2AF1 subtypes has already been assigned in MDS, and (iii) there is laboratory information that suggests functional differences between U2AF1-splice site interactions for S34 vs. Q157 variants [ 8 , 9 ].
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Tefferi et al. (2018) studied this question.