Fig. 2: CNAs and RUNX1-ETS2 fusion in CML-CP and BC.

a Sequencing-based copy-number profiling in CML-CP and BC samples from 52 cases. Frequencies of copy-number gains or losses are depicted along the chromosomal regions. b RUNX1-ETS2 fusion detected in a patient (TW-CML-M-001) by conducting WES analysis. Sanger sequencing of cDNA obtained from the BC samples was used to validate the fusion breakpoint (top). Simplified scheme of RUNX1-ETS2 fusion (bottom). Inversion 21 involves the RUNX1 and ETS2 genes for generation of the fusion. The karyotyping result of this sample at CP diagnosis was as follows (results at BC diagnosis were not obtained): 47,XY,+8,inv(9)(p11q13),t(9;22)(q34;q11). c Time chart showing dynamic changes in RUNX1-ETS2 and BCR-ABL1 burdens assessed by RT-qPCR at several time points in a patient (TW-CML-M-001). The horizontal and vertical axes represent the time from CP diagnosis (Dx) and levels of the indicated transcripts, respectively. The patient received imatinib (Ima) treatment after CP diagnosis and achieved CHR, while the BCR-ABL1 burden was not reduced significantly. Approximately 15 months after CP diagnosis, there was an abrupt development of BC, which was successfully treated with cytarabine and hydroxyurea in addition to imatinib. Thereafter, BCR-ABL1 transcript levels showed continuous reductions, and were below the threshold of CMR at 15 years after BC diagnosis. The RUNX1-ETS2 transcript was detected at the time of CP diagnosis and increased markedly during BC development, declined following chemotherapy with imatinib, and was undetectable 4 years after BC transformation.