Cytokines, Genetic Lesions and Signaling Pathways in Anaplastic Large Cell Lymphomas
Abstract
:Simple Summary
Abstract
1. Main ALCL Subtypes
1.1. Systemic ALK+ ALCL
1.2. Systemic ALK- ALCL
1.3. Cutaneous ALCL
1.4. Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL)
2. ALCL Oncogenesis
2.1. ALCL Cell of Origin
2.2. ALK+ ALCL
2.3. STAT3 a Pivotal Transcription Factor in Most ALCL Subtypes
2.4. STAT3-Independent ALK- ALCLs
3. Cytokines in ALCLs
3.1. Detection and Monitoring of Cytokines
3.2. Cytokines in ALK+ ALCL
3.3. Signaling through IL-2R Activates the JAK/STAT Pathway in Cutaneous ALCL
3.4. Cytokines in BIA-ALCL
3.5. Cytokines Modify the Microenvironment and Pathology
3.5.1. BIA-ALCL
3.5.2. C-ALCL and CD30+ CLPD
3.6. Does Cytokine Profile Indicate the Cell of Origin or Maturation Stage of ALCLs?
3.6.1. Systemic ALCL
3.6.2. BIA-ALCL
4. Therapy of ALCLs
4.1. Front-Line Treatments
4.2. Targeted Therapies
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Acknowledgments
Conflicts of Interest
References
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Categories | Systemic ALK+ ALCL | Systemic ALK- ALCL | Cutaneous ALCL | BIA-ALCL |
---|---|---|---|---|
Patient age/gender | Children/adolescents | Adults | Elderly males | Women |
Prognosis | Good | Poor | Excellent | Excellent |
Treatment | Multiagent chemotherapy | Brentuximab-vedotin | Surgery, radiation, methotrexate | Capsulectomy |
Extent of disease | Lymph nodes and frequent extranodal disease | Widespread | Skin with/without regional lymph nodes | Localized to breast |
Pathology | Sheets of anaplastic cells, fibrosis in Hodgkin-like variant | Sheets of anaplastic cells | Sheets of anaplastic cells, frequent neutrophils | Individual and clusters of anaplastic cells often at capsule surface, frequent eosinophils |
ALCL Subtype | Predominant Phenotype | Differentiation | Gene Rearrangement | Mutations | Signaling Pathways | Therapeutic Targets |
---|---|---|---|---|---|---|
Systemic ALK+ ALCL | CD30+ ALK+, EMA+, CD3+, CD4+, CD3-CD4-CD5-Cytotoxic | T-cytotoxic Th17/Th22, | ALKwith NPM1 80% | STAT3 | CD30, ALK, JAK | |
Systemic ALK- ALCL | CD30+ ALK-, CD3+, CD4+, CD3-CD4-CD5-, Cytotoxic | T-cytotoxic | TP63 (12.5%) DUSP22 rare | JAK-STAT | STAT3 ERBB4 | CD30, JAK, HER |
Cutaneous ALCL | CD30+, ALK-, EMA-, CD4+, CD2-CD3-CD5-, CLA+, Cytotoxic LEF1 | Th2 /Th17 | DUSP22 (30%) TP63 (10%) ALK * exceptional | MSCE116KDUSP22 rare | CD30-IRF4-MYC Th2 signaling | CD30 pSTAT6 |
Th2 | NPM-TYK2 | TYK2 | STAT1 STAT6 | TYK | ||
BIA-ALCL | CD30+, ALK-, EMA+, TCR- CD4+ > CD8+ Cytotoxic | Th2 | - | JAK-STAT and epigenetic modifiers | STAT3 STAT6 | CD30, JAK pSTAT6 |
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Merlio, J.-P.; Kadin, M.E. Cytokines, Genetic Lesions and Signaling Pathways in Anaplastic Large Cell Lymphomas. Cancers 2021, 13, 4256. https://doi.org/10.3390/cancers13174256
Merlio J-P, Kadin ME. Cytokines, Genetic Lesions and Signaling Pathways in Anaplastic Large Cell Lymphomas. Cancers. 2021; 13(17):4256. https://doi.org/10.3390/cancers13174256
Chicago/Turabian StyleMerlio, Jean-Philippe, and Marshall E. Kadin. 2021. "Cytokines, Genetic Lesions and Signaling Pathways in Anaplastic Large Cell Lymphomas" Cancers 13, no. 17: 4256. https://doi.org/10.3390/cancers13174256
APA StyleMerlio, J. -P., & Kadin, M. E. (2021). Cytokines, Genetic Lesions and Signaling Pathways in Anaplastic Large Cell Lymphomas. Cancers, 13(17), 4256. https://doi.org/10.3390/cancers13174256