RNA-seq data analysis of CD123 loss samples

Molecular analysis of CD123 loss following UCART123 treatment. Overall design: The RNA were extracted from CD123- cells or CD123+ cells from UCART123 treated mice in PDX-3 experiment. In the PDX study, mice treated with UCART123 experienced CD123-negative relapse. Unexpectedly, we identified not a single, but three diverse mechanisms of CD123 loss amongst mice that relapsed with CD123- disease: genomic loss of CD123 DNA; a truncated transcript containing only exons 2-9; and predominant alternative splicing (skipping from exon 2 to exon 5) which is reminiscent of CD19 epitope loss in B-cell acute lymphoblastic leukemia36. The most plausible explanation is the selection of a small pre-existing population of clones lacking CD123, that were enriched upon the selective pressure of UCART123 therapy.