U5 small nuclear ribonucleoprotein 200 kDa helicase (SNRNP200)-Low affinity immunoglobulin gamma Fc region receptor II-a (CD32A) complex (SNRNP200-CD32A)

The U5 snRNP-specific 200 kDa helicase (SNRNP200), also known as Brr2, is a nuclear RNA helicase essential for the catalytic activation of the spliceosome (NIH, 2023). In certain hematological malignancies, such as acute myeloid leukemia (AML) and B-cell acute lymphoblastic leukemia (B-ALL), SNRNP200 is aberrantly expressed on the cell surface in a physical complex with the Fc receptor CD32A (FcγRIIA) (ResearchGate, 2023). This surface translocation is dependent on the transmembrane domain of CD32A and is notably absent from normal hematopoietic stem and progenitor cells, although it is present on normal B cells (AACR Journals, 2024). The SNRNP200-CD32A complex represents a unique class of cancer-specific surface antigens derived from mislocalized nuclear proteins. While SNRNP200 typically functions in the nucleus to unwind U4/U6 RNA duplexes, its presence on the leukemia cell membrane provides a therapeutic window for immune-based interventions (NIH, 2023). Experimental therapies targeting this complex, including Fc-optimized monoclonal antibodies and chimeric antigen receptor (CAR) T cells, have demonstrated efficacy in human and syngeneic models of AML (AACR Journals, 2024). Pro-inflammatory cytokines like IFNγ and IL-18 have been shown to upregulate the surface expression of this complex, potentially enhancing the efficacy of targeted treatments (HHS, 2025). However, the expression of the complex on normal B cells necessitates careful monitoring for B-cell aplasia in clinical settings. Ongoing research continues to explore the functional role of this complex in leukemia cell survival and its potential as a biomarker for disease progression (HHS, 2025).

Other names

Brr2-CD32A complexU5-200kD-FcγRIIA complexSNRNP200-FCGR2A complexHELIC2-CD32A complexU5 snRNP-specific 200 kDa helicase in aberrant surface complex with CD32A/FcγRIIASNRNP200CD32AFCGR2ABrr2

Antibody-dependent cellular cytotoxicity (ADCC) and T-cell mediated cytotoxicity targeting the aberrant surface complex.