IDH1 and IDH2 mutation analysis in chronic- and blast-phase myeloproliferative neoplasms

Bone marrow DNA was screened for isocitrate dehydrogenase ( IDH ) mutations in 200 patients with chronic ( n =166) or blast ( n =34) phase myeloproliferative neoplasms (MPN). Included among the former were 77 patients with primary myelofibrosis (PMF), 47 essential thrombocythemia and 38 polycythemia vera (PV). Nine IDH mutations (5 IDH1 and 4 IDH2 ) were detected; mutational frequencies were ∼21% (7 of 34) for blast-phase MPN and ∼4% (3 of 77) for PMF. IDH mutations were seen in only 1 of 12 paired chronic-blast-phase samples and in none of 27 concurrently studied acute myeloid leukemia (AML) patients without antecedent MPN. IDH1 mutations included R132C ( n =4; two post-PMF AML, one post-PV AML and one PMF) and R132S ( n =1; post-PMF AML). IDH2 mutations included R140Q ( n =3; one post-PMF AML, one post-PV AML and one PMF) and a novel R140W ( n =1; mutation found in both chronic- and blast-phase samples). The entire study cohort was also screened for JAK2 and MPL mutations and JAK2 V617F was found in three IDH -mutated cases (two PMF and one PV). This study shows a relatively high incidence of IDH mutations in blast-phase MPN, regardless of JAK2 mutational status, and the occurrence of similar mutations in chronic-phase PMF.