The prognostic impact and stability of Isocitrate dehydrogenase 2 mutation in adult patients with acute myeloid leukemia
Journal
Leukemia
Journal Volume
25
Journal Issue
2
Pages
246-253
Date Issued
2011
Author(s)
Lei W.-C.
Chen C.-Y.
Chang Y.-C.
Lee F.-Y.
Liu M.-C.
Liu C.-W.
Tseng M.-H.
Huang C.-F.
Abstract
Although the clinical features of the Isocitrate dehydrogenase 2 (IDH2) mutation in acute myeloid leukemia (AML) have been characterized, its prognostic significance remains controversial and its stability has not been investigated. We analyzed 446 adults with primary non-M3 AML and found IDH2 R172, R140 and IDH1 R132 mutations occurred at a frequency of 2.9, 9.2 and 6.1%, respectively. Compared with wild-type IDH2, mutation of IDH2 was associated with higher platelet counts, intermediate-risk or normal karyotype and isolated 8, but was inversely correlated with expression of HLA-DR, CD34, CD15, CD7 and CD56, and was mutually exclusive with WT1 mutation and chromosomal translocations involving core-binding factors. All these correlations became stronger when IDH1 and IDH2 mutations were considered together. Multivariate analysis revealed IDH2 mutation as an independent favorable prognostic factor. IDH2 /FLT3-ITD genotype conferred especially negative impact on survival. Compared with IDH2 R140 mutation, IDH2 R172 mutation was associated with younger age, lower white blood cell count and lactate dehydrogenase level, and was mutually exclusive with NPM1 mutation. Serial analyses of IDH2 mutations at both diagnosis and relapse in 121 patients confirmed high stability of IDH2 mutations. In conclusion, IDH2 mutation is a stable marker during disease evolution and confers favorable prognosis. ? 2011 Macmillan Publishers Limited All rights reserved.
SDGs
Other Subjects
CD15 antigen; CD34 antigen; CD56 antigen; CD7 antigen; HLA DR antigen; isocitrate dehydrogenase; isocitrate dehydrogenase 1; isocitrate dehydrogenase isoenzyme; lactate dehydrogenase; nucleophosmin; unclassified drug; acute granulocytic leukemia; adult; aged; antigen expression; article; cancer diagnosis; cancer relapse; cancer survival; chromosome translocation; controlled study; cytogenetics; female; gene mutation; genetic association; genotype; human; immunophenotyping; karyotype; leukocyte count; major clinical study; male; molecular cloning; multivariate analysis; priority journal; prognosis; thrombocyte count; wild type
Publisher
Nature Publishing Group
Type
journal article