Clinical Applications of Genomic Alterations in ATLL: Predictive Markers and Therapeutic Targets
Abstract
:Simple Summary
Abstract
1. Introduction
2. Overview of Genomic Alterations of ATLL
3. Mutations of Genes Involved in TCR/NF-κB Signaling
4. Immune Escape Mechanisms in ATLL
5. Heterogeneity of Genomic Alterations in ATLL: Geographic Region and Age at Diagnosis
6. Characteristic Genomic Alterations in ATLL Compared with Other PTCLs
7. Genomic Alterations in ATLL as Prognostic Markers
8. Precision Targets from ATLL Genomic Studies
8.1. Mogamulizumab
8.2. Immune Checkpoint Inhibitors
8.3. Lenalidomide
8.4. Other Potential Targeted Therapies
9. Targetable Super-Enhancers in ATLL
10. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Gene | ATLL Entire Japan [20] (n = 370) | ATLL North America [21] (n = 30) | ATLL Young Japanese [22] (n = 8) | PTCL-NOS [27] (n = 133) | AITL [27] (n = 26) | ALCL [27] (n = 23) | ENKTL [27] (n = 25) | HSTL [28] (n = 68) |
---|---|---|---|---|---|---|---|---|
PLCG1 | 36 | 0 | 0 | 8 | 8 | 0 | 0 | 6 |
PRKCB | 33 | NE | 13 | 0 | 0 | 0 | 0 | NA |
CCR4 | 29 | NE | 38 | 4 | 0 | 0 | 0 | 2 |
CARD11 | 24 | 7 | 38 | 3 | 0 | 0 | 0 | 2 |
STAT3 | 21 | 0 | 0 | 5 | 8 | 13 | 12 | 10 |
TP53 | 18 | 23 | 13 | 17 | 0 | 9 | 12 | 10 |
VAV1 | 18 | NE | 0 | 6 | 8 | 0 | 0 | NA |
TBL1XR1 | 17 | 13 | 0 | 4 | 0 | 0 | 0 | NA |
NOTCH1 | 15 | 20 | 25 | 5 | 0 | 0 | 0 | NA |
GATA3 | 15 | 7 | 0 | 0 | 0 | 0 | 0 | NA |
IRF4 | 14 | NE | 13 | 1 | 0 | 0 | 0 | 16 |
FAS | 11 | 0 | 0 | 4 | 0 | 4 | 0 | NA |
CCR7 | 11 | NE | 25 | 2 | 0 | 0 | 0 | NA |
POT1 | 10 | 7 | 0 | 2 | 4 | 4 | 0 | NA |
IRF2BP2 | 8 | NE | NE | 2 | 0 | 0 | 0 | NA |
TET2 | 8 | 7 | 13 | 43 | 88 | 4 | 0 | 6 |
RHOA | 8 | 3 | 13 | 26 | 81 | 0 | 0 | 2 |
HLA-B | 6 | NE | 0 | 5 | 4 | 4 | 0 | NA |
HNRNPA2B1 | 6 | NE | 0 | 0 | 0 | 4 | 0 | NA |
EP300 | 6 | 20 | 0 | 2 | 0 | 0 | 8 | NA |
CD58 | 5 | NE | 0 | 4 | 0 | 9 | 0 | 0 |
GPR183 | 5 | NE | NE | 1 | 0 | 0 | 0 | NA |
CSNK1A1 | 5 | NE | NE | 0 | 0 | 0 | 0 | NA |
CSNK2B | 5 | NE | NE | 1 | 0 | 0 | 0 | NA |
CBLB | 4 | NE | 0 | 0 | 0 | 0 | 0 | NA |
FYN | 4 | NE | 13 | 2 | 0 | 0 | 0 | 3 |
B2M | 4 | 0 | 0 | 5 | 8 | 0 | 0 | NA |
SETD2 | 3 | 0 | 0 | 3 | 0 | 0 | 0 | 22 |
Alteration | Targets | Clinical Outcome | Reference |
---|---|---|---|
CNA of cell cycle-related genes | Chronic type | Early acute transformation | [19] |
Del of CD58 | Chronic type | Early acute transformation | [19] |
PRKCB mutation | Aggressive type | Poor prognosis | [70] |
Amp of PD-L1 | Aggressive type | Poor prognosis | [70] |
IRF4 mutation | Indolent type | Poor prognosis | [70] |
Amp; PD-L1 | Indolent type | Poor prognosis | [70] |
Del; CDKN2A | Indolent type | Poor prognosis | [70] |
Putative Targets | Potential Drugs | Active, or Recruiting Trials Including the Potential Drugs |
---|---|---|
CCR4 | Mogamulizumab | NCT04185220 |
PD1/PD-L1 | Pembrolizumab | |
IRF4 | Lenalidomide | NCT04301076 |
proteolysis targeting chimera | ||
EZH1/2 | Valemetostat Tosylate | NCT04102150 |
Histone deacetylases | Belinostat | NCT02737046 |
Romidepsin | NCT04639843 | |
Phosphatidylinositol 3-kinase | Duvelisib | NCT04639843 |
CD30 | Brentuximab | NCT03113500 |
Anti-CD30 CAR-T | NCT04008394 | |
DNA methylation | 5-azacitidine | NCT04639843 |
OR-2100 | ||
PRKCB | MS-533 | |
proteolysis targeting chimera | ||
MALT1 | JNJ-67856633 | |
MDM2/MDM4 | ALRN-6924 |
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Yoshida, N.; Miyoshi, H.; Ohshima, K. Clinical Applications of Genomic Alterations in ATLL: Predictive Markers and Therapeutic Targets. Cancers 2021, 13, 1801. https://doi.org/10.3390/cancers13081801
Yoshida N, Miyoshi H, Ohshima K. Clinical Applications of Genomic Alterations in ATLL: Predictive Markers and Therapeutic Targets. Cancers. 2021; 13(8):1801. https://doi.org/10.3390/cancers13081801
Chicago/Turabian StyleYoshida, Noriaki, Hiroaki Miyoshi, and Koichi Ohshima. 2021. "Clinical Applications of Genomic Alterations in ATLL: Predictive Markers and Therapeutic Targets" Cancers 13, no. 8: 1801. https://doi.org/10.3390/cancers13081801
APA StyleYoshida, N., Miyoshi, H., & Ohshima, K. (2021). Clinical Applications of Genomic Alterations in ATLL: Predictive Markers and Therapeutic Targets. Cancers, 13(8), 1801. https://doi.org/10.3390/cancers13081801