title: IDH1 and IDH2 mutation analysis in chronic- and blast-phase myeloproliferative neoplasms.
abstract: 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 approximately 21% (7 of 34) for blast-phase MPN and approximately 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.
authors.affiliation: Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: A
authors.initials: A
authors.lastname: Pardanani
authors.forename: T L
authors.initials: TL
authors.lastname: Lasho
authors.forename: C M
authors.initials: CM
authors.lastname: Finke
authors.forename: M
authors.initials: M
authors.lastname: Mai
authors.forename: R F
authors.initials: RF
authors.lastname: McClure
authors.forename: A
authors.initials: A
authors.lastname: Tefferi
mesh_terms: D000368:Aged; D001752:Blast Crisis / Q000235:genetics* / Q000473:pathology; D001853:Bone Marrow; D002908:Chronic Disease; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D053614:Janus Kinase 2 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009196:Myeloproliferative Disorders / Q000235:genetics* / Q000473:pathology; D053628:Receptors, Thrombopoietin / Q000235:genetics
chemical_list: D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; D053614:Janus Kinase 2