Complex exon structure of CD19 and CD22 mRNA isoforms revealed by long-read Oxford Nanopore sequencing

B-cell acute lymphoblastic leukaemia (B-ALL) is the most common paediatric malignancy. CD19-CART immunotherapy has revolutionised its treatment.

CD19 alternative splicing was investigated with long-read nanopore direct cDNA and RNA sequencing, which obtained full-length profiles of CD19.

CD19 alternative splicing is associated with resistance to CAR T-cell immunotherapy.

Splicing of CD22, an alternative therapeutic target, was studied with nanopore sequencing; full-length transcripts revealed the complexity of CD22 isoforms.

Mukta summarised her talk stating that alternative splicing of target surface antigens, such as CD19 and CD22, generates many functional proteins which may impart resistance to immunotherapies such as CAR T-cells.