title: Acquired somatic mutations of isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2) in preleukemic disorders.
abstract: Mutations of isocitrate dehydrogenase isoform 1 and 2 (IDH1 and IDH2) genes have been identified in glioblastoma and acute myeloid leukemia (AML). However, little is known about the molecular alterations of IDH genes in preleukemic disorders with a propensity to transform to AML. We performed polymerase chain reaction-denaturing high performance liquid chromatography (PCR-DHPLC) followed by direct sequencing to detect IDH mutations in 237 patients with myeloproliferative neoplasms (MPNs; n=108), myelodysplastic syndrome (MDS; n=22), paroxysmal nocturnal hemoglobinuria (PNH; n=41), and aplastic anemia (AA; n=66). No IDH1 R132 and IDH2 R172 mutations were identified in the entire cohort, whereas IDH1 G105G allele was detected in 4/108 MPN (3.70%), 2/22 MDS (9.09%), and 2/41 PNH (4.88%) patients. Three IDH2 R140Q mutations were found in 2/108 MPN (1.85%) and 1/22 MDS (4.54%) patients, while one IDH2 G145G allele was found in 0.92% (1/108) of MPN patients. Overall, our data suggest that IDH mutations are rare in the preleukemic disorders and may not be the major initial step in AML leukemogenesis.
authors.affiliation: Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. Electronic address: sadudee.chotirat@gmail.com.
authors.forename: Sadudee
authors.initials: S
authors.lastname: Chotirat
authors.affiliation: Office of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. Electronic address: nathongnop@gmail.com.
authors.forename: Wanna
authors.initials: W
authors.lastname: Thongnoppakhun
authors.affiliation: Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. Electronic address: wanchai.wan@mahidol.ac.th.
authors.forename: Wanchai
authors.initials: W
authors.lastname: Wanachiwanawin
authors.affiliation: Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. Electronic address: chirayuaue@yahoo.com.
authors.forename: Chirayu U
authors.initials: CU
authors.lastname: Auewarakul
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000741:Anemia, Aplastic / Q000235:genetics*; D001483:Base Sequence; D015331:Cohort Studies; D005260:Female; D006457:Hemoglobinuria, Paroxysmal / Q000235:genetics*; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D009196:Myeloproliferative Disorders / Q000235:genetics*; D011110:Polymorphism, Genetic; D055815:Young Adult
chemical_list: C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human
keywords: Aplastic anemia; IDH mutations; Myelodysplastic syndrome; Myeloproliferative neoplasms; Paroxysmal nocturnal hemoglobinuria; Preleukemia disorders