Table 3.
Select mutations in HSTCL and associated targeted therapies
| Pathway | Class of targeting therapy | Targeted therapies |
|---|---|---|
| Chromatin modifiers | ||
| SETD2, INO80, TET3, and | Histone deacetylase inhibitors | Vorinostat, romidepsin |
| SMARCA2, ARID1, DNMT3A | Hypomethylating agents | Decitabine, azacitidine |
| EZH2 | EZH2 inhibitors | Tazemetostat, valemetostat, CPI1205 |
| IDH2 | IDH inhibitors | Enasidenib |
| JAK/STAT | ||
| STAT5B, STAT3 | JAK inhibitors | Ruxolitinib, fedratinib |
| PI3K | ||
| PIK3CD | PI3K inhibitors | Idelalisib, copanlisib, duvelisib, alpelisib |
| NK-cell antigens | ||
| KIR3DL2, KIR2DS2, KIR3DS1 | Killer immunoglobulin-like receptor antibodies | Lirilumab (KIR2DL1/2L3) |
| KIR2DL2 | IPH4102 (KIR3DL2) | |
| NCAM1, CD244, S1PR5, CD16 (NK-cell homing to the spleen) | N/A | N/A |
| KLR | N/A | N/A |
| Growth factors | ||
| IGFBP, AREG (amphiregulin), PDGFD | Tyrosine kinase inhibitors | Imatinib, dasatinib, ponatinib nilotinib, sunitinib, axitinib, pazopanib, regorafenib, lenvatinib, nintedanib |
| Cell-trafficking genes | ||
| S1PR5 | N/A | N/A |
| Multidrug resistance | ||
| ABCB1 | N/A | N/A |
| Tyrosine kinase | ||
| SYK | SYK inhibitor | Fostamatinib |
| Chemokines | ||
| CXCL7 (PPBP), CXCL6 | N/A | N/A |
| Cell adhesion | ||
| VCAM1, CD11d, ICAM1 | N/A | N/A |
| WNT pathway | ||
| FRZB, TCF7L2, BAMBI, TLE1, CTNNB1, APC, and FZD5 | N/A | N/A |
| Microenvironment | ||
| Hemoglobin γ, β, and α | N/A | N/A |
| DEFA1/DEFA1B/ DEFA3 CCL3 (MIP1) | ||
| Tumor suppressors | ||
| KRAS, TP53 | N/A | N/A |
| Others | ||
| CREBBP, RUNDC3B, PPP1R9A, UBR5 | N/A | N/A |
N/A, not applicable.