Analysis of RBP expression and binding sites identifies PTBP1 as a regulator of CD19 expression in B-ALL.

ABSTRACT: Despite massive improvements in the treatment of B-ALL through CART-19 immunotherapy, a large number of patients suffer a relapse due to loss of the targeted epitope. Mutations in the CD19 locus and aberrant splicing events are known to account for the absence of surface antigen. However, early molecular determinants suggesting therapy resistance as well as the time point when first signs of epitope loss appear to be detectable are not enlightened so far. By deep sequencing of the CD19 locus, we identified a blast-specific 2-nucleotide deletion in intron 2 that exists in 35% of B-ALL samples at initial diagnosis. This deletion overlaps with the binding site of RNA binding proteins (RBPs) including PTBP1 and might thereby affect CD19 splicing. Moreover, we could identify a num

SUBMITTER: Ziegler N 

PROVIDER: S-EPMC9980455 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature