Acute myeloid leukemia with isolated del(5q) is associated with IDH1/IDH2 mutations and better prognosis when compared to acute myeloid leukemia with complex karyotype including del(5q).
We conclude that IDH1(R)¹³² and IDH2(R)¹⁷² mutations occur most often in cytogenetically normal AML cases with an overall frequency of approximately 11.8%.
This review surveys the use of tyrosine kinase inhibitors to treat patients with mutant FLT3 AML, mutant KIT AML, as well as IDH inhibitors and explores some questions regarding their integration into the treatment armamentarium for AML.
We studied 805 adults (age range, 16 to 60 years) with AML enrolled on German-Austrian AML Study Group (AMLSG) treatment trials AML HD98A and APL HD95 for mutations in exon 4 of IDH1 and IDH2.
In the hematopoietic system, mutations in IDH1 at arginine (R) 132 and in IDH2 at R140 and R172 are commonly observed in acute myeloid leukemia, and elevated 2HG is observed in cells and serum.
Mutations in isocitrate dehydrogenase 1 (IDH1) drive most low-grade gliomas and secondary glioblastomas and many chondrosarcomas and acute myeloid leukemia cases.
We measured D2HG serum levels in 84 patients with IDH-mutated AML treated in the prospective, randomized multicenter AML2003 trial of the German Study Alliance Leukemia.
Mutation at the R132 residue of isocitrate dehydrogenase 1 (IDH1), frequently found in gliomas and acute myelogenous leukemia, creates a neoenzyme that produces 2-hydroxyglutarate (2-HG) from α-ketoglutarate (α-KG).
Although the first reports have also already emerged describing acquired resistance for these mutant IDH inhibitors, combination treatment might overcome this problem, which could drastically change the treatment landscape of AML over the next few years.
The frequency of IDH1/2 mutations was 56%, and the IDH1R132C mutation, which is not common in diffuse gliomas or AML, accounted for 40% of these mutations.
Comparison of HRM to Sanger sequencing on 146 AML bone marrow samples for validation showed near-perfect concordance for all positive and negative results for IDH1 (98%) and IDH2 (94%).
Mutations in isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) occur in most grade 2 and 3 gliomas, secondary glioblastomas, and a subset of acute myelogenous leukemias but have not been detected in other tumor types.
The single-nucleotide polymorphism (SNP) (reference SNP no. rs11554137:C>T) located on IDH1 codon 105 has been associated with a poor outcome in patients with acute myeloid leukemia but has not been investigated in patients with gliomas.
Acquired somatic mutations of IDH1 and IDH2 have recently been reported in some types of brain tumors and a small proportion of acute myeloid leukemia (AML) cases.
Mutations were mutually exclusive with IDH(mut), which supported recent data on a common mechanism of action that might obscure the impact of TET2(mut) if compared against all other patients with AML.
In conclusion, our study showed a high frequency of FLT3, RUNX1, and IDH mutations in AML-M0, suggesting that these mutations played a role in the pathogenesis and served as potential therapeutic targets in this rare and unfavorable subtype of AML.
In particular, these results provide an additional rationale supporting the combination of FLT3 and mutant IDH1 inhibitors as a promising clinical treatment of mutant IDH1-positive AML.<i>See related commentary by Horton and Huntly, p. 699</i>.<i>This article is highlighted in the In This Issue feature, p. 681</i>.