KEY TAKEAWAYS
- The study aimed to investigate the role of AXL activation in the progression of SCC in early-stage, untreated patients with CLL.
- Researchers found that AXL drives SCC in CLL, suggesting AXL inhibition as a potential therapy.
Occurrence of squamous cell carcinoma (SCC), even in patients with early-stage, untreated chronic lymphocytic leukemia (CLL), presents a significant morbidity risk, with instances of transformation into metastatic skin lesions.
Sutapa Sinha and the team aimed to investigate the underlying mechanisms contributing to SCC development in patients with CLL, focusing on the potential role of AXL signaling in driving cancer progression.
They performed an inclusive analysis involving the purification of CLL cells and extracellular vesicles (EVs) from the blood/plasma of patients with CLL. The expression and activation of AXL were assessed, focusing on its functions in normal keratinocytes (HEKa) using an in vitro co-culture system. Additionally, AXL activity was evaluated in SCC tissues to understand its role in the progression of squamous cell carcinoma in patients with CLL.
About the results, researchers detected aberrant activation of AXL, AKT, and ERK-1/2 in SCC cell lines compared to HEKa. They also observed increased expression of AXL in primary SCC tissues obtained from patients with CLL. Increased activation of AXL, AKT, ERK-1/2, and Src was discernible in HEKa upon co-culturing with CLL cells.
Further analysis suggests that Gas6, a ligand of AXL, regulates AXL activation in co-cultured HEKa. Interestingly, exposure of HEKa cells to CLL plasma-derived EVs induced the expression of AXL, P-AKT, and EMT-associated markers, leading to cell migration. Finally, pharmacologic inhibition of AXL-induced cell death in SCC lines in a dose-dependent manner.
The study concluded that CLL cells are likely involved in driving SCC progression, at least in part, via activation of the AXL signaling axis. This indicates that AXL inhibition may be beneficial for CLL patients with SCC.
This study was funded by Mayo Internal Funding.
Source: https://pubmed.ncbi.nlm.nih.gov/38886556/
Sinha S, Guo R, Del Busso MD, et al. (2024). “Aberrant activation of AXL may drive progression of squamous cell carcinoma in CLL patients: a mechanistic study with clinical implications.” Br J Cancer. 2024 Aug;131(3):589-600. doi: 10.1038/s41416-024-02752-1. Epub 2024 Jun 17. PMID: 38886556; PMCID: PMC11300914.
