BCP-ALL blasts are not dependent on CD19 expression for leukaemic maintenance

In recent years the anti-CD19/anti-CD3 bispecific antibody blinatumomab and chimeric antigen receptor (CAR) modified T cells targeting CD19 have shown early efficacy in clinical trials of paediatric and adult B-cell precursor acute lymphoblastic leukaemia (BCP-ALL).1, 2, 3, 4, 5 The rationale behind targeting CD19 in BCP-ALL is primarily its homogenous cell surface expression and B-lineage specificity.5 Thus, the entire malignant cell population should be targeted and eradicated by anti-CD19-directed immunotherapies. CD19 would be expected to have important functions in BCP-ALL survival, based on its roles in enhancing pre-B-cell receptor (pre-BCR) mediated phosphoinositide 3-kinase (PI3K) signalling and through pre-BCR-independent pathways such as MYC activation.6, 7, 8, 9 However, the effects of CD19 depletion on BCP-ALL cells have not been investigated. Hence, we examined the role of CD19 in leukaemic maintenance by silencing its expression in BCP-ALL cell lines and primograft samples using RNA interference.