TETRASPANIN CD9 AND CD81: DIFFERENTIAL REGULATION AND POTENTIAL ROLES IN CHEMORESISTANCE IN ACUTE AND CHRONIC LYMPHOCYTIC LEUKEMIA

Аннотация

Abstract

Tetraspanins (TSPANs) are a family of transmembrane proteins implicated in diverse cellular processes, including signal transduction and cell adhesion.  While their precise functions are still being elucidated, their involvement in cancer, particularly leukemia, is increasingly recognized. This study focuses on the multifaceted roles of two specific TSPANs, CD9 and CD81, in acute lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia (CLL), with a specific emphasis on their impact on chemotherapy response.  Previous research has established CD9 as a prognostic marker in B-cell ALL (B-ALL), with expression correlating with specific genetic subtypes and glucocorticoid resistance.  However, its role in other leukemia subtypes and its precise contribution to chemoresistance remain incompletely understood.  Similarly, CD81 has been shown to mediate chemoresistance in B-ALL by facilitating protective interactions with the bone marrow microenvironment, but its significance in CLL and its broader impact on chemotherapy sensitivity require further investigation.  This study addresses these gaps by investigating the expression of CD9 and CD81 in ALL and CLL patients, stratified by chemotherapy regimen, including vincristine (VCR), methotrexate (MTX), and doxorubicin (DOXO).  Our results demonstrate a statistically significant upregulation of both CD9 and CD81 at the gene and protein levels in ALL patients treated with chemotherapy compared to controls.  Furthermore, we observed significant upregulation of CD9 in untreated CLL patients, while no significant difference in CD9 or CD81 expression was found between the ALL and CLL groups.  These findings strongly suggest a critical role for CD9 and CD81 in mediating chemoresistance in ALL, particularly in the context of VCR, MTX, and DOXO treatment.  Based on these observations, we discuss potential mechanisms by which CD9 and CD81 contribute to leukemogenesis and propose that targeting these TSPANs may represent a novel therapeutic strategy to overcome chemoresistance and improve patient outcomes in leukemia.