Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 May 15;118(10):2665-73.
doi: 10.1002/cncr.26580. Epub 2011 Oct 21.

Prognostic significance of alterations in IDH enzyme isoforms in patients with AML treated with high-dose cytarabine and idarubicin

Farhad Ravandi  1 , Keyur Patel, Rajyalakshmi Luthra, Stefan Faderl, Marina Konopleva, Tapan Kadia, Mark Brandt, Sherry Pierce, Steven Kornblau, Michael Andreeff, Xuemei Wang, Guillermo Garcia-Manero, Jorge Cortes, Hagop Kantarjian
Affiliations

Prognostic significance of alterations in IDH enzyme isoforms in patients with AML treated with high-dose cytarabine and idarubicin

Farhad Ravandi et al. Cancer. .

Abstract

Background: IDH1 and IDH2 gene mutations are novel, recurring molecular aberrations among patients with normal karyotype acute myeloid leukemia (AML).

Methods: Among 358 patients with AML treated on 4 protocols using high-dose ara-C plus idarubicin induction, pretreatment samples were available for 170 (median age 53 years, [range, 17-73]; 96% ≤65) and were evaluated for IDH1R132, IDH2R172, and IDH2R140 mutations or the codon 105 single nucleotide polymorphism (SNP) in IDH1.

Results: IDH1 and IDH2 mutations were present in 12 (7%) and 24 (14%) of patients, and IDH1 G105 SNP in 24 (14%). Overall, 52 (30%) patients had IDH gene alterations. There was no association with complete response (CR), remission duration, overall survival, and event-free survival and any of the IDH alterations, and no association with a higher CR rate or survival with the 4 regimens for the 52 patients with aberrant IDH. Among the patients with diploid karyotype and NPM1(mut) FLT3(WT) genotype, those with IDH1 or IDH2 mutations had an inferior outcome.

Conclusions: IDH aberrations and IDH1 codon 105 SNP occur in about 30% of younger patients with AML, mostly with diploid karyotype. Using high-dose ara-C-based induction regimens, we did not detect an association with outcome for any of the aberrations.

PubMed Disclaimer

Figures

Figure 1
Figure 1
a Survival among patients with diploid karyotype by the presence of IDH1 mutation b Survival among patients with diploid karyotype by the presence of IDH1 G105 SNP c Survival among patients with diploid karyotype by the presence of IDH2 mutations
Figure 1
Figure 1
a Survival among patients with diploid karyotype by the presence of IDH1 mutation b Survival among patients with diploid karyotype by the presence of IDH1 G105 SNP c Survival among patients with diploid karyotype by the presence of IDH2 mutations
Figure 1
Figure 1
a Survival among patients with diploid karyotype by the presence of IDH1 mutation b Survival among patients with diploid karyotype by the presence of IDH1 G105 SNP c Survival among patients with diploid karyotype by the presence of IDH2 mutations
Figure 2
Figure 2
a Survival for patients with IDH mutations or G105 SNP (dubbed “IDH positive) versus other b Event-free survival for patients with IDH mutations or G105 SNP (dubbed “IDH positive) versus other c Complete remission duration for patients with IDH mutations or G105 SNP (dubbed “IDH positive) versus other
Figure 2
Figure 2
a Survival for patients with IDH mutations or G105 SNP (dubbed “IDH positive) versus other b Event-free survival for patients with IDH mutations or G105 SNP (dubbed “IDH positive) versus other c Complete remission duration for patients with IDH mutations or G105 SNP (dubbed “IDH positive) versus other
Figure 2
Figure 2
a Survival for patients with IDH mutations or G105 SNP (dubbed “IDH positive) versus other b Event-free survival for patients with IDH mutations or G105 SNP (dubbed “IDH positive) versus other c Complete remission duration for patients with IDH mutations or G105 SNP (dubbed “IDH positive) versus other
Figure 3
Figure 3
a Survival in patients with diploid karyotype and NPM1mut/FLT3WT genotype by the presence of absence of IDH1 R132 b Survival in patients with diploid karyotype and NPM1mut/FLT3WT genotype by the presence of absence of IDH2 mutations c Survival of patients with diploid karyotype and FLT3-ITD by the presence or absence of IDH1 R132
Figure 3
Figure 3
a Survival in patients with diploid karyotype and NPM1mut/FLT3WT genotype by the presence of absence of IDH1 R132 b Survival in patients with diploid karyotype and NPM1mut/FLT3WT genotype by the presence of absence of IDH2 mutations c Survival of patients with diploid karyotype and FLT3-ITD by the presence or absence of IDH1 R132
Figure 3
Figure 3
a Survival in patients with diploid karyotype and NPM1mut/FLT3WT genotype by the presence of absence of IDH1 R132 b Survival in patients with diploid karyotype and NPM1mut/FLT3WT genotype by the presence of absence of IDH2 mutations c Survival of patients with diploid karyotype and FLT3-ITD by the presence or absence of IDH1 R132
See this image and copyright information in PMC

References

    1. Haselbeck RJ, McAlister-Henn L. Function and expression of yeast mitochondrial NAD- and NADP-specific isocitrate dehydrogenases. J Biol Chem. 1993;268:12116–12122. - PubMed
    1. Plaut GW, Cook M, Aogaichi T. The subcellular location of isozymes of NADP-isocitrate dehydrogenase in tissues from pig, ox and rat. Biochim Biophys Acta. 1983;760:300–308. - PubMed
    1. Sjoblom T, Jones S, Wood LD, et al. The consensus coding sequences of human breast and colorectal cancers. Science. 2006;314:268–274. - PubMed
    1. Parsons DW, Jones S, Zhang X, et al. An integrated genomic analysis of human glioblastoma multiforme. Science. 2008;321:1807–1812. - PMC - PubMed
    1. Bleeker FE, Lamba S, Leenstra S, et al. IDH1 mutations at residue p.R132 (IDH1(R132)) occur frequently in high-grade gliomas but not in other solid tumors. Hum Mutat. 2009;30:7–11. - PubMed