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 similar to 21% (7 of 34) for blast-phase MPN and similar to 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 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. Leukemia (2010) 24, 1146-1151; doi:10.1038/leu.2010.77; published online 22 April 2010