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 (n166) or blast (n34) 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 (n4; two post-PMF AML, one post-PV AML and one PMF) and R132S (n1; post-PMF AML). IDH2 mutations included R140Q (n3; one post-PMF AML, one post-PV AML and one PMF) and a novel R140W (n1; mutation found in both chronic-and blast-phase samples). The entire study cohort was also screened for JAK2 and MPL mutations and JAK2V617F 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.