IDH2 mutation + SRSF2 mutation

The discovery of clonal hematopoiesis in this elderly woman with a wide spectrum of severe auto-inflammatory conditions supports a potentially intriguing link between somatic blood mutations and her adult- onset rheumatologic disorders. Mechanistically, disrupted SRSF2-mediated splicing may be driving aberrant antigen presentation by bone marrow-derived dendritic cells in her skin and other organs. Causal relationships between somatic blood mutations and autoimmune/auto-inflammatory conditions have been established in patients with hematologic malignancies and conditions like VEXAS syndrome.

Three family members had pre-existing mild thrombocytopaenia of 100-110x109/l, with normal sized platelets on blood smear examination. They were registered at the local haemophilia centre with a mild platelet function defect requiring tranexamic acid and/or platelet transfusions for procedures. Platelet aggregometry showed normal response to ristocetin 1.25mg/ml, a reduced slope and disaggregation to arachidonic acid, epinephrine and collagen, with no demonstrable release to adenosine diphosphate (ADP).

Interestingly the higher risk of AML transformation and the worse PFS in DNMT3A R882 mutant MDS cases are mitigated by coexisting SF3B1 or SRSF2 mutations. The unique clinicopathologic features of DNMT3A R882 mutant MDS shed light on the prognostic and therapeutic implications of DNMT3A R882 mutations.

The unique clinicopathologic features of DNMT3A R882 mutant MDS shed light on the specific prognostic and therapeutic implications of DNMT3A R882 mutations.