Protein Drives Tumorigenesis in B-Cell Tumors
(ChemotherapyAdvisor) – CD19 is a major driver of tumorigenesis in B-cell tumors, according to researchers of the University of Pennsylvania, Philadelphia, PA, and The Children's Hospital of Philadelphia, Philadelphia, PA. The researchers made this conclusion in a paper entitled “CD19 is a major B cell receptor–independent activator of MYC-driven B-lymphomagenesis,” which was published in the Journal of Clinical Investigation on May 1.
The investigators' research aims were based on previous studies, which demonstrated that PAX5 is a B-cell–specific transcription factor that is overexpressed through chromosomal translocations in a subset of B-cell lymphomas. Studies have also demonstrated that activation of immunoreceptor tyrosine-based activation motif (ITAM) proteins and B-cell receptor (BCR) signaling by PAX5 contributes to B-lymphomagenesis. The investigators aimed to determine the unknown effect of PAX5 on other oncogenic transcription factor-controlled pathways.
The research was conducted using a MYC-induced murine lymphoma model as well as MYC-transformed human B-cell lines. Based on experiments in this system, the investigators reported that PAX5 controls c-MYC protein stability and steady-state levels. “This promoter-independent, posttranslational mechanism of c-MYC regulation was independent of ITAM/BCR activity. Instead it was controlled by another PAX5 target, CD19, through the PI3K-AKT-GSK3β axis,” the investigators wrote. “Expression of CD19 in murine lymphomas with spontaneous silencing of PAX5 boosted MYC levels… cell proliferation in vitro, and overall tumor growth in vivo… and negatively correlated with the overall survival of patients with lymphoma in the same way that MYC levels do.”
The authors concluded: “CD19 is a major BCR-independent regulator of MYC-driven neoplastic growth in B-cell neoplasms.”