SRP286918 PRJNA668379 GSE159331 Targeted nanopore sequencing for the identification of ABCB1 promoter translocations in relapsed acute myeloid leukemia [Targeted Resequencing] Resistance to chemotherapy is the most common cause of treatment failure in acute myeloid leukemia and the drug efflux pump ABCB1 is a critical mediator. Here we demonstrate that in vitro daunorubicin exposure can induce activating ABCB1 promoter translocations in human myeloid cells, similar to those recently described in recurrent high-grade serous ovarian and breast cancer. We then develop a targeted nanopore sequencing approach that enables efficient identification of ABCB1 structural variants in high-grade serous ovarian cancer. Finally, we confirm that ABCB1high cases of relapsed AML are not characterized by ABCB1 promoter translocations but instead show high-level activity of native promoters, consistent with endogenous regulation. Overall design: THP-1 cells were from DSMZ (Braunschweig, Germany) and cultured in RPMI 1640 medium (Sigma Aldrich) supplemented with 2mM L-Glutamine (Life Technologies, Carlsbad, CA) and 10% fetal bovine serum (Sigma Aldrich). Whilst under drug selection cells were counted and replated every third day. Cell lines were confirmed mycoplasma-free and authenticated by short tandem repeat DNA profiling. THP-1 were exposed to escalating doses of daunorubicin over 142 days, generating a resistant line (THP-1_R) which exhibited a 28.3-fold increase in daunorubicin IC50 compared with the sensitive parental cell line (THP-1_S). Known to contain an ABCB1 promoter fusion, THP-1_R was subjected to genomic target enrichment and sequencing by both long-read nanopore sequencing and conventional illumina sequencing (this data). GSE159331 pubmed 33167906 parent_bioproject PRJNA669673