Clinicopathologic characterisation of myeloid neoplasms with concurrent spliceosome mutations and myeloproliferative-neoplasm-associated mutations.

AIMS

Spliceosome genes (, , and ) are commonly mutated in myeloid neoplasms, particularly in myelodysplastic syndromes (MDS). , and mutations are associated with myeloproliferative neoplasms (MPN). Although and MPN-associated mutations frequently co-occur in the rare entity MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T), myeloid neoplasms with concurrent spliceosome and MPN-associated mutations encompass many disease entities and are not well characterised.

METHODS

Specimens from 2016 to 2019 with concurrent spliceosome and MPN-associated mutations were identified, and the clinicopathologic features were assessed.

RESULTS

The 36 cases were divided into mutational categories based on their spliceosome mutation. At diagnosis, cases with concurrent and MPN-associated mutations had lower leucocyte counts and platelet counts than did the other groups. Cases with mutant were more likely to have and mutations, while mutated neoplasms were more likely to have an abnormal karyotype. The most common K700 and S34 mutational hotspots were underrepresented in our cohort of myeloid neoplasms with concurrent spliceosome and MPN-associated mutations, as and mutations tended to involve other codons. Numerous WHO-defined disease entities were represented in each spliceosome gene category; although MDS/MPN-RS-T were only identified in the group with mutations, they constituted only 1/4 of the neoplasms in the category.

CONCLUSIONS

Myeloid neoplasms with different mutant splicing factor and concurrent MPN-associated mutations demonstrate somewhat different clinical and pathologic features, but t he association between genotypes and phenotypes in these overlapping neoplasms is not straightforward.