Recent development in whole-genome and whole-exome sequencing has accelerated integrated molecular analyses of genetic alterations in ATL. According to the intensive studies, the genetic alterations in ATL are found in various pathways such as T cell receptor (TCR)/NF-κB pathway (PLCγ1, PRKCβ, CARD11, VAV1, CD28, FYN, CD247, DLG1, PRKCQ, ERC1, IKBKB, RELA, PAK2), chemokine receptor (CCR4, CCR7, GRP183), tumor suppressor (TP53, CKDN2A, TP73), transcriptional regulation (IRF4, IRF2BP2, GATA3, PRDM1, IKZF2), other signaling (NOTCH1, STAT), immune evasion (PD-L1, PDCD1, CD58, B2M, HLA-A, HLA-B, FAS), and epigenetic regulation (TET2, DNMT3A, IDH2, EP300).
It should be noted that the genetic mutations in the TCR/NF-κB pathway inducing constitutive activation of the NF-κB signaling pathway is observed in more than 90% of ATL cases. This result obtained by the whole-genome sequencing of ATL cells is well compatible with the previous reports on the activated expression of NF-κB in almost all the ATL cases.
Author(s) Details:
Mitsuru Sakitani,
Institute CCC, Kobe, Hyogo, 651-2242, Japan.
