IDH mutations have been observed among various groups of patients, including those with glioblastoma multiforme, grade 2 and 3 gliomas, and secondary glioblastomas, as well as patients with acute myeloid leukemia. However, limited data exist among patients with Philadelphia-negative myeloproliferative neoplasms.
As part of this study, Ipek Yonal-Hindilerden, from the Division of Hematology at the Department of Internal Medicine, Istanbul University, Turkey, and colleagues evaluated the prevalence and prognostic significance of IDH1 and IDH2 mutations, using high-resolution melting analysis, among 77 patients with primary myelofibrosis, 107 patients with essential thrombocythemia, and 184 patients with Philadelphia-negative myeloproliferative neoplasms. In addition, clinical and hematologic parameters were evaluated.
At the beginning of the study, the investigators collected data, including patient demographics, laboratory samples such as blood counts, lactate dehydrogenase levels, and noted complications (eg, bleeding and thrombosis). IDH1 (R132) and IDH2 (R140 and R172) mutations were genotyped, and JAK2V617F allele burden was quantified.
When comparing patients with essential thrombocythemia and primary myelofibrosis, Dr Yonal-Hindilerden and colleagues observed no significant difference in prevalence of IDH mutations or combined JAK2V617F and IDH mutations. Specifically, 6.5% of patients with primary myelofibrosis had IDH1 or IDH2 mutations, of which 3 patients had IDH1 R132C mutation, 1 patient had an IDH1 R132S substitution, and 1 patient had an IDH2 R140Q mutation. Three of the 5 patients with IDH-mutated primary myelofibrosis carried the JAK2V617F mutation, with allele burdens of 31% to 50%, 5% to 12.5%, and 31% to 50%, respectively.
In addition, 1.9% (2 of 107 cases) of patients with essential thrombocythemia had IDH1 or IDH2 mutations. There was not a higher rate of IDH mutation among women, the study authors noted. Among these patients, there was 1 who had IDH1 R132C substitution, and 1 with IDH2 R140Q mutation; the latter had a JAK2V617F mutation with a 5% allele burden, whereas the former did not carry the JAK2V617F mutation.
Taking a closer look at patient data, the investigators observed that there was a higher trend of IDH mutations among women with primary myelofibrosis. Compared with patients with primary myelofibrosis carrying wild-type IDH, patients with IDH mutations had a significantly higher rate of bleeding complications, a lower prevalence of acetylsalicylic acid use, and a higher death rate.
"IDH mutations had significant impact on [leukemia-free survival] in patients [with primary myelofibrosis]," Dr Yonal-Hindilerden and colleagues concluded in the Journal of Clinical Medicine & Research. "Despite the limited number of IDH-mutated patients [with primary myelofibrosis] included, our observations support that IDH mutations provide genetic events in the pathogenesis and prognosis of [primary myelofibrosis] patients. Clearly, screening for IDH mutation might be added to future clinical trials and prospective observational studies in [primary myelofibrosis]."
Yonal-Hindilerden I, Daglar-Aday A, Hindilerden F, et al. The clinical significance of IDH mutations in essential thrombocythemia and primary myelofibrosis.J Clin Med Res. 2016;8:29-39.