Table 4.
Molecular subtyping schemes of ENKTCL published in recent years.
| Author | Subtype | Representative genomic alterations or immune characteristics | Prognosis | Potentially effective treatment |
|---|---|---|---|---|
| Xiong et al. (213) | HEA | Mutations in HDAC9, EP300, and ARID1A | Good | HDAC inhibitor |
| TSIM | Mutations in JAK-STAT pathway and TP53, ampJAK2 locus; amp17q21.2/STAT3/5B/5A locus, amp9p24.1/PD-L1/2 locus, del6q21 | Intermediate | PD-1 blockade | |
| MB | MGA mutation, 1p22.1/BRDT LOH | Poor | MYC inhibition | |
| Dong et al. (214) | C1 | Higher CN complexity including gains and losses of 17q21(STAT3), 8q24(MYC), and del19q | Intermediate | - |
| C2 | KMT2D mutation and chr2 gain | Intermediate | - | |
| C3 | NOTCH2 mutation and del17p | Intermediate | - | |
| C4 | DDX3X mutation and del1p36 | Intermediate | - | |
| C5 | CN gain of chr19q/q13 and JAK3 gain | Good | - | |
| C6 | Aberrations in RAS/RAF/MAPK pathway, JAK3, BCOR, and TP53 | Poor | - | |
| C7 | TET2 loss and ARID1B mutation | Good | - | |
| Lim et al. (215) | GPM | Mutations in BCOR, JAK3, KRAS, MYH11, DCC, ITK, NOTCH1, FAS, RET, BIRC3, MLLT1, LRP1B, NRG1 | Poor | - |
| Cho et al. (217) | Immune tolerance | High-Treg counts (> 500/HPF) | Good | Good response to PD-1 blockage |
| Immune evasion-A | High cytotoxic T-cell counts, high PD-L1 expression, low Treg counts (PD-L1 > 10%) | Intermediate | Intermediate response to PD-1 blockage | |
| Immune evasion-B | Not otherwise specified | Intermediate | Intermediate response to PD-1 blockage | |
| Immune silenced | Immune response exhausted (Process-type CD68 > 90%) | Poor | Poor to PD-1 blockage |