TSPAN5: A Potential Biomarker for Methotrexate Resistance in Acute Lymphoblastic Leukemia in Iraq

The transmembrane receptor family known as tetraspanins (TSPANs) was integral to diverse cellular processes, including protein anchoring, scaffolding, and signal transduction. While the functional repertoire of TSPANs is still being elucidated, their involvement in cancer development and progression is increasingly recognized. Specifically, tetraspanin 5 (TSPAN5) has been implicated in modulating key cellular behaviors such as survival, proliferation, and invasion. Critically, our previous work established a crucial role for TSPAN5 in the development of chemoresistance against conventional chemotherapeutics, including vincristine (VCR), methotrexate (MTX), and doxorubicin (DOXO), in malignant cells and no untreated cases. This study comprehensively reviews and analyzes current understanding of TSPAN5's physiological mechanisms in ALL and CLL, with a particular emphasis on its contribution to chemoresistance. We report a statistically significant upregulation of TSPAN5 in ALL patients stratified by chemotherapy regimen compared with untreated cases, specifically within the cohort treated with MTX (p < 0.0001). Although elevated TSPAN5 levels were observed in the VCR-only and DOXO-treated groups, these increases did not reach statistical significance. Furthermore, TSPAN5 expression in untreated CLL patients was comparable to controls; there was no discernible variation in TSPAN5 expression between the ALL and CLL groups. These results offer strong proof that TSPAN5 contributes to chemotherapy resistance in ALL, especially when MTX is used as a treatment. In light of these findings, we talk about the possible ways that TSPAN5 functions in leukemogenesis and suggest that focusing on TSPAN5 might be a useful therapeutic approach for overcoming chemoresistance and enhancing leukemia treatment results.