Type 1 CALR mutations in ET, as evident in the patient described herein, are also associated with a higher risk of myelofibrotic transformation although the biological mechanism(s) for this have yet to be clarified: impaired calcium signalling and calcium binding activity to mutant CALR protein have been preferentially demonstrated in type 1 CALR mutated MPN [39]. This evidence concerns the gene CALR and myeloproliferative neoplasm.