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

The Protein tyrosine phosphatase receptor type C-CYRI-B (PTPRC-CYRIB) fusion protein is a novel chimeric molecule identified in patients with primary drug-resistant T-cell acute lymphoblastic leukemia (T-ALL) (Li et al., 2024; Blood). This fusion involves PTPRC (also known as CD45), a critical receptor-type protein tyrosine phosphatase that regulates T- and B-cell antigen receptor signaling, and CYRI-B (FAM49B), a regulator of the WAVE complex involved in actin dynamics (UniProt P08575; UniProt Q9H6U6). The PTPRC-CYRIB fusion acts as an oncogenic driver, significantly increasing the proliferation rate and clonogenic potential of leukemic cells (Li et al., 2024; Blood). Crucially, its expression has been shown to confer resistance to standard induction chemotherapy regimens, specifically reducing the efficacy of vincristine, idarubicin, cyclophosphamide, and prednisone (Li et al., 2024; Blood). Because it drives both disease progression and treatment failure, the PTPRC-CYRIB fusion protein is considered a significant biomarker for refractory T-ALL and a potential therapeutic target for precision medicine interventions. Targeting the fusion protein specifically could minimize the risks associated with inhibiting wild-type CD45, which is essential for normal immune function (UniProt P08575). Current research focuses on characterizing the downstream signaling pathways activated by this fusion to identify vulnerable nodes for pharmacological intervention (Li et al., 2024; Blood).

Other names

CD45-FAM49B fusion proteinPTPRC-FAM49B fusion proteinCD45-CYRIB fusion protein

The fusion protein promotes leukemic cell proliferation and confers resistance to standard chemotherapy agents (vincristine, idarubicin, cyclophosphamide, and prednisone) by altering intracellular signaling pathways; no specific inhibitors are currently approved.