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. 2010 Oct;95(10):1668-74.
doi: 10.3324/haematol.2010.025494. Epub 2010 May 21.

IDH1 mutations in patients with myelodysplastic syndromes are associated with an unfavorable prognosis

Felicitas Thol  1 , Eva M Weissinger, Jürgen Krauter, Katharina Wagner, Frederik Damm, Martin Wichmann, Gudrun Göhring, Christiane Schumann, Gesine Bug, Oliver Ottmann, Wolf-Karsten Hofmann, Brigitte Schlegelberger, Arnold Ganser, Michael Heuser
Affiliations

IDH1 mutations in patients with myelodysplastic syndromes are associated with an unfavorable prognosis

Felicitas Thol et al. Haematologica. 2010 Oct.

Abstract

Background: Myelodysplastic syndromes are a heterogeneous group of hematopoietic stem cell disorders with a high propensity to transform into acute myeloid leukemia. Heterozygous missense mutations in IDH1 at position R132 and in IDH2 at positions R140 and R172 have recently been reported in acute myeloid leukemia. However, little is known about the incidence and prognostic impact of IDH1 and IDH2 mutations in myelodysplastic syndromes.

Design and methods: We examined 193 patients with myelodysplastic syndromes and 53 patients with acute myeloid leukemia arising from myelodysplastic syndromes for mutations in IDH1 (R132), IDH2 (R172 and R140), and NPM1 by direct sequencing.

Results: We found that mutations in IDH1 occurred with a frequency of 3.6% in myelodysplastic syndromes (7 mutations in 193 patients) and 7.5% in acute myeloid leukemia following myelodysplastic syndromes (4 mutations in 53 patients). Three mutations in codon R140 of IDH2 and one mutation in codon R172 were found in patients with acute myeloid leukemia following myelodysplastic syndromes (7.5%). No IDH2 R140 or R172 mutations were identified in patients with myelodysplastic syndromes. The presence of IDH1 mutations was associated with a shorter overall survival (HR 3.20; 95% CI 1.47-6.99) and a higher rate of transformation into acute myeloid leukemia (67% versus 28%, P=0.04). In multivariate analysis when considering karyotype, transfusion dependence and International Prognostic Scoring System score, IDH1 mutations remained an independent prognostic marker in myelodysplastic syndromes (HR 3.57; 95% CI 1.59-8.02; P=0.002).

Conclusions: These results suggest that IDH1 mutations are recurrent molecular aberrations in patients with myelodysplastic syndromes, and may become useful as a poor risk marker in these patients. These findings await validation in prospective trials.

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Figures

Figure 1.
Figure 1.
Description of patients’ samples. MDS, myelodysplastic syndrome; AML, acute myeloid leukemia
Figure 2.
Figure 2.
Kaplan-Meier curves for overall and event-free survival. (A) Overall survival in MDS patients with mutated (n= 7) and unmutated (n=146) IDH1 (log-rank test, P=0.002). (B) Event-free survival in MDS patients (n=153) with mutated (n= 7) and unmutated (n=146) IDH1 (log-rank test, P=0.02).
See this image and copyright information in PMC

Comment in

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