Fig. 5: Proposed model of IKAROS-mediated antigen escape in the face of CD19- and CD22-targeted therapies.

Before immunotherapy, IKAROS^low pro-B-like B-ALL cells possess chromatin and gene expression states poised for loss of B-cell identity while maintaining expression of CD19 and CD22. Under immune pressure, IKAROS^high cells maintain their antigen expression, making them more susceptible to T cell-mediated killing. Conversely, IKAROS^low cells are more likely to downregulate their antigen expression, giving them a relative advantage to escape immunotherapies, resulting in antigen escape relapse. Created in BioRender⁸¹.