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Abstract
Philadelphia negative and JAK2-V617F negative myeloproliferative neoplasms (MPN Ph-/JAK2-) frequently carry mutations in other genes, namely calreticulin (CALR), thrombopoietin receptor (MPL) or in another region (exon 12) of JAK2 (ex12JAK2). These mutations have clinical relevance and contribute to the present diagnostic algorithm. Furthermore, the type of mutation is a new prognostic factor in certain situations. Thus, we did a retrospective study of the mutational profile of CALR, MPL and ex12JAK2 in patients with diagnosis or suspicion of MPN Ph-/JAK2-. We did 296 molecular tests in 238 cases (53 ET, 10 MF, 6 PV and 169 only characterized as potential MPN). We observed 56 mutations in CALR (29%): 41% type 1 deletion, 37% type 2 insertion and the remaining 22% were other variants, 3 of them not previously described. These unique variants were observed only en ET. In the MPL gene we found 3 mutations (6%): W515L (2) and W515K (1). We did not detect any ex12JAK2 mutation in peripheral blood. Among those patients with a confirmed diagnosis, CALR was mutated in 49% of ET and 40% MF while MPL was mutated in 2% and 10%, respectively. No PV showed mutation in these genes. In diagnosed patients, these frequencies of mutations were as expected, similar to the mutational profile in the literature. All mutations were mutually exclusive. Our mutational analyses allowed confirmation of clonality in a subgroup of patients under evaluation for MPN, therefore contributing to the diagnosis.
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