A targeted mutational landscape of angioimmunoblastic T-cell lymphoma

Abstract

Key Points AITL is characterized by high frequencies of overlapping mutations in epigenetic modifiers, including TET2, IDH2, and DNMT3A. Targetable mutations are present in a subset of cases.

Emerging therapeutic targets in myeloproliferative neoplasms and peripheral T-cell leukemia and lymphomas

“…In AITL, IDH2 and TET2 mutations were detected in the same patients, which is not the case in myeloid malignancies [77]. In AITL and PTCL-NOS, TET2 mutations were associated with a worse prognosis [96].…”

“…In AITL, PTCL-NOS and CTCL subtypes, DNMT3A mutations cluster in the methyltransferase domain. Interestingly, only about 20% of these mutations are at position R882 [75,77,94,95,97], the variant commonly found in myeloid diseases acting as a negatively regulating hypomorphic protein [105]. Dnm3a -deficient mice develop a PTCL-like disease at a frequency of 12% and heterozygous animals at a rate of 10%, associated with hypomethylation and decreased TP53 activity [106].…”

“…TET2 and DNMT3A mutations likely occur early during evolution of hematopoietic neoplasms and are even detectable in apparently healthy individuals [99,107]. These mutations can also co-occur which emphasizes the importance of disrupted DNA and histone methylation in PTCL [77]. …”

Romidepsin induces durable responses in patients with relapsed or refractory angioimmunoblastic T‐cell lymphoma

“…These results provide additional support for the use of romidepsin in relapsed/refractory AITL. Further study of responding patients, particularly in light of discoveries of frequent DNMT3A , TET2 , IDH2 , and RhoA mutations in AITL,16, 17 may lead to biomarkers for sensitivity to HDACi.…”

Aspects moléculaires des lymphomes T périphériques (1)

“…Les mutations de TET2 sont observées chez environ 60 à 70 % des patients [22][23][24][25][26][27] et 2 de ces mutations sont présentes dans presque la moitié des cas [22,23]. Elles sont réparties sur la totalité du gène et sont de nature inactivatrice (mutations des sites d'épissage, mutations non-sens, faux-sens dans des régions conservées dans l'évolution).…”