The genetic changes in chronic myeloid leukaemia (CML) have been well elucidated, but challenges persist in cases with rare fusion transcripts or complex variant translocations. Here, we present a CML patient with e14a3 BCR-ABL1 transcript and t(9;22;12) variant Philadelphia (Ph) chromosome.
Cytogenetic analysis and fluorescence in situ hybridisation (FISH) was performed to identify the chromosomal aberrations and gene fusions. Rare fusion transcript was verified by reverse transcription-polymerase chain reaction (RT-PCR). Breakpoints were characterised and validated using Oxford Nanopore Technologies (ONT) and Sanger sequencing, respectively.
The karyotype showed the translocation t(9;22;12)(q34;q11.2;q24)[20], and FISH indicated 40% positive BCR-ABL1 fusion signals. RT-PCR suggested e14a3 type fusion transcript. The ONT sequencing analysis identified specific positions of translocation breakpoints: chr22:23633040-chr9:133729579, chr12:121567595-chr22:24701405, which were confirmed using Sanger sequencing. The patient achieved molecular remission 3 months after imatinib therapy.
The study indicates Nanopore sequencing as a valid strategy, which can characterise breakpoints precisely in special clinical cases with atypical structural variations (SVs). CML patients with e14a3 transcripts may have good clinical course in the tyrosine kinase inhibitor (TKI) era, as reviewed here.

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