Clinical Relevance of IDH1 and IDH2 Mutations and Single Nucleotide Polymorphism (SNP) rs11554137 in Patients with Acute Myeloid Leukemia Treated with Stem Cell Transplant in First Complete Remission

Mutations in the genes encoding for the cytosolic isocitrate dehydrogenase 1 (IDH1) and the mitochondrial version of this enzyme (IDH2) have been reported in acute myeloid leukemia (AML) and other types of cancer. Presence of these mutations in AML correlated with more aggressive disease in some studies, but other studies did not find significant correlation with outcome when patients were treated with intensive chemotherapy. The polymorphism at rs11554137 in IDH1 was reported to correlate with inferior outcome in cytogenetically normal AML patients. Most of the studies evaluating the prognostic relevance of IDH1, IDH2 and the rs11554137 polymorphism were reported in patients treated with standard chemotherapy. The prognostic significance of these markers is not fully studied when AML patients are treated with intensive chemotherapy followed by allogeneic hematopoietic stem cell transplantation (HSCT). We studied the prognostic value of the IDH1, IDH2, and rs11554137 polymorphism in patients with AML treated with HSCT in first complete remission (CR1).

Samples from 69 patients with AML were analyzed for mutations in IDH1, IDH2, and the SNP rs11554137 by direct sequencing. All patients were diagnosed with AML, treated with chemotherapy followed by HSCT in CR1. They included intermediate (N=42) and adverse (N=27) cytogenetic risk groups.

The R132H and the SNP C to T change at rs11554137 (silent G105) in IDH1 were detected in 5 (7%) and 6 (9%) of 69 AML patients. The IDH2 mutations (N=5; 7%) included R140Q, 172K, and T169A. Patients with IDH1 or IDH2 mutations did not differ significantly in their overall survival, event free survival, or time to relapse from those without mutation. In addition, the rs11554137 SNP polymorphism did not correlate with outcome in this group of AML patients. We also looked at the combination of mutations as compared with cytogenetic risk and found no difference in survival or event free survival based on IDH1 or IDH2 mutations or rs11554137 polymorphism in the intermediate cytogenetic risk group.

The data suggests that HSCT after intensive chemotherapy in CR1 may neutralize the negative prognostic impact of IDH1 and IDH2 or the rs11554137 SNP polymorphism. However, the number of cases is relatively small and further studies with larger number of cases are needed.

No relevant conflicts of interest to declare.