Novel Fusion Gene PTPRC-Cyrib As a Drug Resistance Mechanism in T-ALL

To investigate the mechanisms of resistance conferred by the novel fusion gene PTPRC-CYRIB in T-cell acute lymphoblastic leukemia (T-ALL).

Using next generation sequencing, we identified the novel fusion gene PTPRC-CYRIB in the bone marrow of a primary drug-resistant T-ALL patient, subsequently confirmed its presence by Sanger sequencing. Molecular cloning techniques were employed to construct a plasmid overexpressing the PTPRC-CYRIB gene. Stable overexpression of PTPRC-CYRIB in T-ALL cell lines was achieved via lentiviral transduction. The T-ALL cell line overexpressing PTPRC-CYRIB was designated as the overexpression (OE) group, while the control group (NC) consisted of cells transduced with empty vector. Polymerase chain reaction (PCR) and western blotting (WB) confirmed PTPRC-CYRIB gene expression in transduced cells. Growth curves were plotted to assess proliferation rates, colony formation assays were conducted to evaluate clonogenic potential, and cell counting Kit-8 (CCK8) assays were performed following treatment with Vincristine, Idarubicin, Cyclophosphamide, and Prednisone to determine drug resistance in the OE group compared to the NC group.

We successfully constructed stable T-ALL cell lines overexpressing PTPRC-CYRIB. PCR and WB analysis confirmed PTPRC-CYRIB overexpression in the OE group compared to the NC group. Growth curve analysis revealed significantly increased proliferation rates in the OE group. Colony formation assays demonstrated enhanced clonogenic potential in OE cells. Following drug intervention, CCK8 assays indicated significantly reduced inhibitory effects of Vincristine, Idarubicin, Cyclophosphamide, and Prednisone on proliferation in the OE group compared to the NC group, with statistical significance (P < 0.05).

Overexpression of the fusion gene PTPRC-CYRIB in T-ALL may contribute to the development of drug resistance.

No relevant conflicts of interest to declare.