Somatic Mutations of Isocitrate Dehydrogenases 1 and 2 Are Prognostic and Follow-up Markers in Patients with Acute Myeloid Leukaemia with Normal Karyotype

Background: Mutations in the isocitrate dehydrogenase 1 and 2 ( and ) genes are frequent molecular lesions in acute myeloid leukaemia with normal karyotype (AML-NK). The effects of 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 Methods: In our study samples from 110 adult AML-NK were studied for the presence of and 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.

Results: mutations were found in 25 (23%) patients. + patients tend to have lower CR rate compared to -patients (44% 62.2%, p = 0.152), and had slightly lower disease free survival (12 months 17 months; p = 0.091). On the other hand, the presence of mutations had significant impact on overall survival (2 7 months; p = 0.039). The stability of mutations were studied sequentially in 19 + patients. All of them lost the mutation in CR, and the same mutations were detected in relapsed samples.

Conclusions: Our study shows that the presence of 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, mutations are very stable during the course of the disease and can be potentially used as markers for minimal residual disease detection.