Fig. 2

Nanopore sequencing identifies ABCB1 fusions in ABCB1^high relapsed primary human HGSC but not primary AML. a Image illustrates the GTF2I-ABCB1 translocation. Red Xs indicate absent transcription from normal ABCB1 promoters in THP-1_R AML cells. b Tracks show the GTF2I portion of chimeric reads spanning the GTF2I-ABCB1 translocation generated by nanopore long-read sequencing (MinION; upper panel) and conventional sequencing (MiSeq; lower panel) of THP-1_R. Pink or blue coloring of reads indicates orientation. c ABCB1 expression levels in primary HGSC samples relative to normal human CD34⁺ haematopoietic stem and progenitor cells (HSPCs), as determined by quantitative PCR. Targeted nanopore sequencing was performed on the samples highlighted in pink; samples with a functional ABCB1 intron 1 fusion are marked with asterisks. d ABCB1 intron 1 breakpoints identified in HGSC samples & THP-1_R cells are indicated, together with the partner gene. e ABCB1 expression levels relative to normal human CD34⁺ HSPCs as determined by quantitative PCR in primary relapsed AML samples. Targeted nanopore sequencing was performed on the samples highlighted in pink. Three presentation AML samples are also shown in green. f H3K27Ac ChIPseq tracks showing the acetylation of ABCB1 promoters for nine of the relapsed AML samples shown in (E). For (C), (E) and (F) number indicates Biobank identifier; T = timepoint