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

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ABSTRACT

Background: Mutations 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 methods: In 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.

Results: IDH 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.

Conclusions: Our 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.

No MeSH data available.


Impact of IDH mutation on overall survival (p = 0.039 by Kaplan-Meier method).
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j_raon-2016-0044_fig_001: Impact of IDH mutation on overall survival (p = 0.039 by Kaplan-Meier method).

Mentions: Out of the 85 IDH- patients, 51 (62.2%) achieved CR, while 11/25 (44%) of the IDH+ patients achieved CR. The difference was not statistically significant (p = 0.152). The presence of IDH mutations was not associated with ED (IDH+-36% vs IDH-- 24.7%; p = 0.310), too. Overall 36/110 (32.7%) participants exhibited disease relapse, 6 (24%) IDH+ and 30 (35.3%) IDH- patients. The impact of IDH mutations on DFS failed to reach statistical significance (IDH+- 12 months vs IDH-- 17 months; p = 0.266). In contrast, OS was significantly impaired in the presence of IDH mutations (IDH+-2 months vs IDH--7 months; p = 0.039) (Figure 1).


Somatic mutations of isocitrate dehydrogenases 1 and 2 are prognostic and follow-up markers in patients with acute myeloid leukaemia with normal karyotype
Impact of IDH mutation on overall survival (p = 0.039 by Kaplan-Meier method).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC5120579&req=5

j_raon-2016-0044_fig_001: Impact of IDH mutation on overall survival (p = 0.039 by Kaplan-Meier method).
Mentions: Out of the 85 IDH- patients, 51 (62.2%) achieved CR, while 11/25 (44%) of the IDH+ patients achieved CR. The difference was not statistically significant (p = 0.152). The presence of IDH mutations was not associated with ED (IDH+-36% vs IDH-- 24.7%; p = 0.310), too. Overall 36/110 (32.7%) participants exhibited disease relapse, 6 (24%) IDH+ and 30 (35.3%) IDH- patients. The impact of IDH mutations on DFS failed to reach statistical significance (IDH+- 12 months vs IDH-- 17 months; p = 0.266). In contrast, OS was significantly impaired in the presence of IDH mutations (IDH+-2 months vs IDH--7 months; p = 0.039) (Figure 1).

View Article: PubMed Central - PubMed

ABSTRACT

Background: Mutations 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 methods: In 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.

Results: IDH 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.

Conclusions: Our 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.

No MeSH data available.