Although CD22 expression is present on the majority of B-ALL blasts at diagnosis and is usually retained in patients with CD19-negative relapse following CD19 CAR-T therapy, its expression is more variable than CD19 expression, which potentially could select for more pre-existing CD22-negative or CD22-low-expression blasts following CD22-directed treatment, resulting in a higher risk of relapse. The gene discussed is CD22; the disease is acute lymphoblastic leukemia.