Acquired somatic mutations of isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2) in preleukemic disorders

Chotirat, Sadudee; Thongnoppakhun, Wanna; Wanachiwanawin, Wanchai; Auewarakul, Chirayu

doi:10.1016/j.bcmd.2014.11.017

Cited by 20 publications

(11 citation statements)

References 42 publications

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“…Thus far, there have been few studies concerning IDH mutations in Asian MDS patients. The frequency of IDH mutations found in this study was similar to that identified in 2 previously published studies with southern Chinese MDS patients and 1 small study of 22 MDS patients in Thailand [22,23,28]. However, Lin et al [24 ]reported that the rate of IDH mutations in Taiwanese patients with MDS may be as low as 4.6% (22/477).…”

Section: Discussionsupporting

confidence: 62%

IDH1 Mutation Is an Independent Inferior Prognostic Indicator for Patients with Myelodysplastic Syndromes

Wang¹,

Wang²,

Shan³

et al. 2017

Acta Haematol

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Background: Genomic sequencing technologies have identified isocitrate dehydrogenase (IDH) mutations in haematological malignancies. The prognostic implications of somatic IDH mutation (mIDH) in myelodysplastic syndromes (MDS) remain controversial. Methods: Mutations in IDH1 and IDH2 were detected using genomic sequencing technologies in 97 patients with MDS. Results: Seven (7.2%) mutations were identified: 3 in IDH1 (all R132C) and 4 in IDH2 (3 R140Q and 1 R140L). The frequency of mutation was 16.6% (2/12) in refractory anaemia with excess blasts (RAEB)-1 and 14.7% (5/34) in RAEB-2. IDH1/2 mutations were closely associated with higher bone marrow blast counts (median 10.0 vs. 2.3%; p = 0.019) and lower absolute neutrophil counts (median 0.44 × 10⁹/L vs. 1.21 × 10⁹/L; p = 0.027). All IDH mutations were mutually exclusive and heterozygous. IDH mutations were not significantly correlated with any specific karyotype. Patients with IDH1 mutations exhibited shorter overall and progression-free survival (OS and PFS; p = 0.039 and p = 0.042, respectively), whereas IDH2 mutations did not affect OS or PFS (p = 0.560 and p = 0.218, respectively). Multivariate analysis indicated that IDH1 mutation (p = 0.018; hazard ratio [HR] 4.735; 95% confidence interval [CI] 1.299-17.264), karyotype risk (p = 0.036; HR 1.619; 95% CI 1.033-2.539) and the revised International Prognostic Scoring System risk category (p < 0.0001; HR 2.122; 95% CI 1.401-3.213) were independent inferior prognostic factors. Conclusions:IDH1 mutation is associated with a poor prognosis.

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Section: Discussionsupporting

confidence: 62%

IDH1 Mutation Is an Independent Inferior Prognostic Indicator for Patients with Myelodysplastic Syndromes

Wang¹,

Wang²,

Shan³

et al. 2017

Acta Haematol

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“…35, 36 In patients with MPN, the acquisition of IDH mutations predicts an increased risk of progression to secondary AML, potentially serving as a marker for early stage transformation. 37–39 Also, the fact that IDH mutations are stable during the course of the disease supports the presumption that their emergence is an early event in malignant transformation.…”

Section: Discussionmentioning

confidence: 70%

Somatic mutations of isocitrate dehydrogenases 1 and 2 are prognostic and follow-up markers in patients with acute myeloid leukaemia with normal karyotype

Virijevic

Karan-Djurašević

Marjanovic

et al. 2016

Radiology and Oncology

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BackgroundMutations in the isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) genes are frequent molecular lesions in acute myeloid leukaemia with normal karyotype (AML-NK). The effects of IDH mutations on clinical features and treatment outcome in AML-NK have been widely investigated, but only a few studies monitored these mutations during follow-up.Patients and methodsIn our study samples from 110 adult de novo AML-NK were studied for the presence of IDH1 and IDH2 mutations, their associations with other prognostic markers and disease outcome. We also analyzed the stability of these mutations during the course of the disease in complete remission (CR) and relapse.ResultsIDH mutations were found in 25 (23%) patients. IDH+ patients tend to have lower CR rate compared to IDH-patients (44% vs 62.2%, p = 0.152), and had slightly lower disease free survival (12 months vs 17 months; p = 0.091). On the other hand, the presence of IDH mutations had significant impact on overall survival (2 vs 7 months; p = 0.039). The stability of IDH mutations were studied sequentially in 19 IDH+ patients. All of them lost the mutation in CR, and the same IDH mutations were detected in relapsed samples.ConclusionsOur study shows that the presence of IDH mutations confer an adverse effect in AML-NK patients, which in combination with other molecular markers can lead to an improved risk stratification and better treatment. Also, IDH mutations are very stable during the course of the disease and can be potentially used as markers for minimal residual disease detection.

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“…IDH mutation frequency was 2.5% in MPNs, 0.8% in ET, 1.9% in PV, 4.1% in PMF, and 1% in post-ET/PV-myelofibrosis patients [5]. Another study reported 3.70% IDH1 (G105G allele), 1.85% IDH2 R140Q, and 0.92% IDH2 (G145G allele) mutation in MPNs [12]. The frequency of the IDH1 (rs11554137) SNP in our cases was similar to that in the literature.…”

Section: Discussionmentioning

confidence: 99%

TET2, ASXL1, IDH1, and IDH2 Single Nucleotide Polymorphisms in Turkish Patients with Chronic Myeloproliferative Neoplasms

Soyer

Kaymaz²,

Özkan³

et al. 2017

Tjh

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We aimed to determine the genotype distribution, allele frequency, and prognostic impact of IDH1/2, TET2, and ASXL1 single nucleotide polymorphisms (SNPs) in myeloproliferative neoplasms (MPNs). TET2 (rs763480), ASXL1 (rs2208131), and IDH1 (rs11554137) variant homozygous genotype frequencies were found at rates of 1.5%, 9.2%, and 2.3%, respectively. No IDH2 SNP was identified. IDH1 and TET2 frequencies were 5% in essential thrombocythemia (ET) and 1.7% in ET and 5% in primary myelofibrosis (PMF), respectively. ASXL1 frequencies were 8.3%-10% in MPN subgroups. The TET2 mutant allele T and ASXL1 mutant allele G had the highest frequencies with 0.272 in the PMF and 0.322 in the polycythemia vera (PV) group, respectively. There was no impact of the SNPs on prognosis. IDH1 frequency in MPNs was found similar to the literature. ASXL1 frequencies were similar between ET, PV, and PMF patients. The ASXL1 and TET2 allele frequencies of the Turkish population are similar to those of the European population. The role of SNPs in MPNs might be further evaluated in larger multicenter studies.

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Acquired somatic mutations of isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2) in preleukemic disorders

Cited by 20 publications

References 42 publications

IDH1 Mutation Is an Independent Inferior Prognostic Indicator for Patients with Myelodysplastic Syndromes

IDH1 Mutation Is an Independent Inferior Prognostic Indicator for Patients with Myelodysplastic Syndromes

Somatic mutations of isocitrate dehydrogenases 1 and 2 are prognostic and follow-up markers in patients with acute myeloid leukaemia with normal karyotype

TET2, ASXL1, IDH1, and IDH2 Single Nucleotide Polymorphisms in Turkish Patients with Chronic Myeloproliferative Neoplasms

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