Analysis of the Main Checkpoints of the JNK-MAPK Pathway in HTLV-1-Associated Leukemia/Lymphoma via Boolean Network Simulation

• Published in: Biochemical genetics 2024-09
• Main Authors: Mardi, Shayan, Letafati, Arash, Hosseini, Amin, Faraji, Reza, Hosseini, Parastoo, Mozhgani, Sayed-Hamidreza
• Format: Article
• Language: English
• ISSN: 0006-2928; 1573-4927; 1573-4927
• DOI: 10.1007/s10528-024-10916-0

The c-Jun N-terminal kinase (JNK) pathway is a signal transduction pathway that plays a critical role in cell growth and survival. Its dysregulation is related to various cancers, including adult T-cell leukemia/lymphoma (ATLL), an aggressive peripheral T-cell malignancy caused by human T-cell lymphotropic virus type 1 (HTLV-1) infection. There is currently no vaccine or definitive treatment for ATLL. This research aimed to identify the JNK-MAPK pathway checkpoints to identify possible therapeutic targets using Boolean network analysis. First, the genes involved in the JNK pathway and their interactions were identified and mapped. Next, a Boolean network analysis was performed using the R programming language, which suggested protein kinase B (AKT) and MAP kinase phosphatase (MKP) for further evaluation. Finally, to confirm the effect of these two genes, a clinical study was conducted among ATLL patients and healthy individuals. The quantitative real time polymerase chain reaction (qRT‒PCR) results revealed a statistically significant decrease in the expression of AKT and MKP in ATLL patients compared to normal controls. This highlights the potential role of these two genes as potential therapeutic targets in ATLL.