Protein tyrosine phosphatase receptor type C-CYRI family protein B fusion gene (PTPRC-CYRIB)

The PTPRC-CYRIB fusion gene is a recurrent chimeric genetic alteration resulting from the fusion of the Protein Tyrosine Phosphatase Receptor Type C (PTPRC, also known as CD45) and the CYRI family protein B (CYRIB, formerly known as FAM49B). This fusion is primarily identified in T-cell acute lymphoblastic leukemia (T-ALL) and is often the result of a chromosomal translocation such as t(1;8)(q31;q24) (PubMed: 28819234). PTPRC is a critical transmembrane phosphatase essential for modulating Src-family kinases in T- and B-cell receptor signaling, while CYRIB acts as a negative regulator of the SCAR/WAVE complex, which governs actin polymerization and cell motility (UniProt: P08575, Q9H0H0). The fusion event typically leads to the aberrant expression of CYRIB or the loss of functional PTPRC phosphatase domains, contributing to leukemogenic transformation by disrupting immune signaling and cytoskeletal homeostasis. While there are currently no approved drugs specifically targeting this fusion protein, it serves as a significant diagnostic biomarker and a potential target for precision medicine in refractory leukemia cases (Blood, 2018).

Other names

CD45-FAM49B fusionPTPRC-FAM49B fusiont(1;8)(q31;q24) fusion

The fusion typically results in the dysregulation of signaling pathways by placing the CYRIB gene under the control of the highly active PTPRC (CD45) promoter or creating a chimeric protein that disrupts normal phosphatase activity and actin dynamics (Nature Communications, 2017).