ALBERT

Description: Background: Angioimmunoblastic T cell lymphoma (AITL) is one of the most frequent peripheral T cell lymphoma, and has a poor prognosis. Neoplastic T cells originate from T follicular helper cells, and are admixed among a prominent microenvironment, making their identification sometimes difficult. IDH2 mutations are present in 20-30% AITL patients, where they often co-exist with TET2, DNMT3A and RHOA mutations. They affect almost exclusively the codon R172 of IDH2, providing to the IDH2 enzyme a neo-activity that converts α ketoglutarate (αKG) to D 2-hydroxyglutarate (2HG). D-2HG, the dextrogyre form of 2HG, is an oncometabolite present at very low level under physiological condition, which inhibits many αKG dependent dioxygenases, including TET proteins and is involved in oncogenesis of various cancers such as gliomas or acute myeloid leukemias (AML). Preliminary data, based on small series, showed that increased level of 2HG was detectable in tumor and in serum of IDH2 mutated AITL. However, 2HG level, as well as D/L ratio, has not been evaluated as a surrogate marker of IDH2 mutation in AITL, at diagnosis or during the follow-up. Patients and Methods: Serum from 69 AITL patients, collected in REVAIL trial (NCT00169156) (N=48), RAIL trial (NCT01553786) (N=9) or TENOMIC collection (N=12) were included in this study. IDH2 mutations were assessed in formalin fixed paraffin embedded tumor tissue by deep next generation sequencing of exon 4, using PGM technology (N=63) or allele specific PCR (N=6). For the purpose of the study the cohort was enriched in mutated patients. Serum was collected at diagnosis and at the end of the frontline treatment in 6 patients, 5 of them being IDH2 mutated. D and L 2HG was measured in serum using a liquid tandem mass spectrometry method as previously described (Poinsignon et al. J Chromatogr B 2016) to determine total (D+L) 2HG and D/L 2HG ratio. Results: Twenty-four patients (35%) were IDH2 mutated. Median IDH2 variant allele frequency (VAF) was 7% (IQR, 4%-12.5%). Median total 2HG was 3.63 µM (IQR, 1.6-6.1) in mutated patients versus 1.17 µM (IQR, 0.85-1.68) in wild type patients (p