In addition to CD22ΔE12, CD22E2 skipping by aberrant splicing [32,33] also occurs in B-ALL, which results in very low CD22E2 mRNA levels and is associated with inherent resistance to CD22-directed immunotherapies such as inotuzumab, ozogamicin, and CAR-T cells [34,35,36] due to reduced expression of the target CD22 protein. This evidence concerns the gene CD22 and acute lymphoblastic leukemia.