Mutations of isocitrate dehydrogenase 1 (IDH1 located on chromosome 2q33. 3) and IDH2 (located on chromosome 15q26. 1) were first described in low-grade gliomas/secondary glioblastomas with a remarkable mutational frequency of B70%. 1 IDH1 and IDH2 mutations have since been described in acute and chronic myeloid malignancies, albeit at a much lower mutational frequency: 2 approximately 1% in essential thrombocythemia (ET), 2% in polycythemia vera (PV), 1% in post-PV/ET myelofibrosis, 4% in primary myelofibrosis, 4% in myelodysplastic syndromes (MDS), 15% in acute myeloid leukemia (AML), 15% in post-MDS AML, 22% in post-MPN AML and 22% in higher-risk MDS or AML associated with isolated 5q-. 3–7 In AML, IDH mutations were significantly associated with normal karyotype, NPM1 mutations and isolated trisomy 8. 8

Trisomy 8 is the most common among sole cytogenetic abnormalities in both AML and MDS with respective incidences of 6 and 11%. 9 In both AML and MDS, trisomy 8 is listed under ‘intermediate-risk cytogenetic group’. Little is known about the pathogenetic effect of trisomy 8 in myeloid malignancies. In the very first report published on IDH mutations in AML, 10 13 of the 16 IDH1 mutations detected were associated with normal karyotype, 2 with trisomy 8 and 1 with trisomy 13. In a subsequent study, 8 20 of 26 IDH1 mutations detected were associated with a normal karyotype, 3 with trisomy 8 and 3 with other abnormalities. Trisomy 8 was also recurrent in patients with IDH1/IDH2-mutated post-MDS AML 11 but not in their counterparts with post-MPN AML. 6 In this study we examined the prevalence and disease distribution of IDH1 and IDH2 mutations in a large (n¼157) group of patients with hematologic malignancies and isolated trisomy 8. After approval by the institutional review board, the Mayo Clinic cytogenetic database spanning the years 1988 through 2008 was queried to identify adult (ageX18 years) cases associated with isolated trisomy 8 in their bone marrow; among 22403 unique patient cytogenetic studies, 157 (0.7%) patients with isolated trisomy 8 were identified. World Health Organization-defined 12 clinical diagnosis at first sighting of trisomy 8 as a sole chromosomal abnormality was de novo MDS in 54 patients, MPN in 32, MDS/MPN in 19, de novo AML in 15, therapy-related MDS/AML in 12, post-MDS AML in 11, post-MPN AML in 1, multiple myeloma in 3, marginal zone lymphoma in 1, diffuse large B-cell lymphoma in 1, angioimmunoblastic lymphoma in 1, T-lymphoblastic leukemia in 1, primary amyloidosis in 1, MDS with concomitant lymphoproliferative neoplasm in 2; the bone marrow was morphologically nondiagnostic in 3 patients. Of note, all the patients with lymphoid malignancies, except the two with T-lymphoblastic leukemia or angioimmunoblastic lymphoma, were previously exposed to chemotherapy, and it is possible that the trisomy 8 abnormality in such cases represented a secondary