CD19 and leukemia: The diverse mechanisms of CD19 downregulation under CD19 immunotherapeutic pressure are impressive, including deletion of the entire CD19 genomic locus, acquisition of CD19 frameshift mutations, alternative CD19 mRNA splicing to remove the targeted epitopes or transmembrane domain, and disruption of CD19 trafficking to the cell membrane, as well as leukemia lineage switch to a myeloid phenotype with concurrent loss of CD19 expression (Figure 2) (Bagashev et al. 2018, Balducci et al. 2017, Braig et al. 2017, Jacoby et al. 2016, Rayes et al. 2016, Sotillo et al. 2015, Zoghbi et al. 2017).