Identifying Novel Therapeutic Targets and Combination Strategies for Patients with BPDCN
Abstract
We used CRISPR interference to perform an unbiased assessment of genes that confer sensitivity or resistance to tagraxofusp or to venetoclax and azacitidine when knocked down. We compared these data to RNA-sequencing of BPDCN cells at baseline and in the setting of MRD after treatment with the same drug. We identified hits in expected pathways that mediate resistance to venetoclax and tagraxofusp. One important hit was a largely uncharacterized RNA binding protein that confers sensitivity to both treatments when depleted. We performed eCLIP-seq to identify targets of this RNA binding protein and are currently performing experiments to understand the mechanism of sensitization.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2022
- Accession Number
- AD1194123
Entities
People
- Andrew A Lane
- Marina Konopleva
- Naveen Pemmaraju
- Omar Abdel-Wahab
Organizations
- Dana–Farber Cancer Institute
- The University of Texas MD Anderson Cancer Center