Characterization, expression, and mutational analysis of endosomal protein lethal giant disc (Lgd/CC2D1A) as a biomarker in patients with T-cell acute lymphoblastic leukemia.

[BACKGROUND] The endosomal pathway plays a crucial role in eukaryotes, and its conservation across evolution underscores its importance in fundamental processes, such as endocytosis, cytokinesis, and autophagy. Dysregulation of the Notch signaling system, essential for growth and development, contributes to cancers like leukemia. In Drosophila melanogaster (DM), specific endosomal genes function as tumor suppressors, regulating Notch signaling, either through promoting Notch degradation or directing its recycling. Nevertheless, it is still unanswered how endosomal genes specifically, lethal giant discs (lgd/CC2D1A), affect Notch-1-mediated transduction in human malignancies, such as T-cell acute lymphoblastic (T-ALL).

[AIM] This study aimed to comprehensively characterize the (lgd/CC2D1A) CC2D1A/lgd in human T-ALL by performing mutational analysis and sequencing and evaluating its gene and protein expression levels. These analyses were conducted to elucidate better the role of (lgd/CC2D1A)CC2D1A in the pathophysiology of T-ALL and to explore its potential association with the Notch-1 signaling pathway.

[MATERIALS AND METHODS] In this study, we sequenced the lgd and investigated its expression in peripheral blood samples of human T-ALL samples. We used molecular approaches to analyse the Lgd/CC2D1A gene for mutations and characterize its gene and protein expression across genomic and proteomic datasets.

[RESULTS] Sequencing data revealed the presence of the lgd variant (CC2D1A) in T-ALL patients and healthy individuals. Lgd and Notch-1 expression were significantly upregulated in T-ALL patients, demonstrating a strong positive correlation at both the genomic and proteomic levels.

[CONCLUSIONS] Through this analysis, we reported the presence of Lgd with an altered nucleotide sequence in T-ALL patients. We also found its elevated expression compared with healthy controls, which might affect disease progression. Our investigation results also lay the foundation for the possible development of Lgd as a predictive indication for the early identification of T-ALL.