<abstract xmlns="http://www.w3.org/1999/xhtml"><sec id="j_raon-2016-0044_s_001_w2aab3b8c47b1b7b1aab1c15b1Aa"><h3>Background</h3><p>Mutations in the isocitrate dehydrogenase 1 and 2 (<italic>IDH1</italic> and <italic>IDH2</italic>) genes are frequent molecular lesions in acute myeloid leukaemia with normal karyotype (AML-NK). The effects of <italic>IDH</italic> 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.</p></sec><sec id="j_raon-2016-0044_s_002_w2aab3b8c47b1b7b1aab1c15b2Aa"><h3>Patients and methods</h3><p>In our study samples from 110 adult <italic>de novo</italic> AML-NK were studied for the presence of <italic>IDH1</italic> and <italic>IDH2</italic> 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.</p></sec><sec id="j_raon-2016-0044_s_003_w2aab3b8c47b1b7b1aab1c15b3Aa"><h3>Results</h3><p><italic>IDH</italic> mutations were found in 25 (23%) patients. <italic>IDH</italic>+ patients tend to have lower CR rate compared to <italic>IDH</italic>-patients (44% <italic>vs</italic> 62.2%, p = 0.152), and had slightly lower disease free survival (12 months <italic>vs</italic> 17 months; p = 0.091). On the other hand, the presence of <italic>IDH</italic> mutations had significant impact on overall survival (2 <italic>vs</italic> 7 months; p = 0.039). The stability of <italic>IDH</italic> mutations were studied sequentially in 19 <italic>IDH</italic>+ patients. All of them lost the mutation in CR, and the same <italic>IDH</italic> mutations were detected in relapsed samples.</p></sec><sec id="j_raon-2016-0044_s_004_w2aab3b8c47b1b7b1aab1c15b4Aa"><h3>Conclusions</h3><p>Our study shows that the presence of <italic>IDH</italic> 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, <italic>IDH</italic> mutations are very stable during the course of the disease and can be potentially used as markers for minimal residual disease detection.</p></sec></abstract>

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.

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

Clinic for Hematology, Clinical Center of Serbia, Belgrade,

Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade,

Medical Faculty, University of Belgrade, Belgrade,

Radiology and Oncology

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

BackgroundMutations in the isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) genes are frequent molecular lesions in acute myeloid leukaemia with normal...

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

Article Category: Research Article

Publicado en línea: 08 sept 2016

Páginas: 385 - 393

Recibido: 28 mar 2016

Aceptado: 18 jun 2016

DOI: https://doi.org/10.1515/raon-2016-0044

© 2016 Radiol Oncol

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.