Identification of a novel CSF3R-SPTAN1 fusion gene in an atypical chronic myeloid leukemia patient with t(1;9)(p34;q34) by RNA-Seq

- CSF3R rearrangement is first found in hematological neoplasms.
- The patient with CSF3R-SPTAN1 fusion showed a poor response to dasatinib therapy.

Membrane-proximal and truncated mutations of colony-stimulating factor 3 receptor (CSF3R) are frequently found in chronic neutrophilic leukemia (CNL) and atypical chronic myeloid leukemia (aCML). However, rearrangement involving CSF3R in hematological neoplasms has not been reported. Here, we report a case of a 21-year-old female diagnosed as aCML with t(1;9)(p34;q34) who presented a CSF3R rearrangement. First, RNA sequencing identified a novel fusion transcript involving exon 17 of CSF3R and exon 50 of non-erythrocytic-1-spectrin-alpha (SPTAN1). Subsequent reverse transcription-polymerase chain reaction (RT-PCR) and bidirectional Sanger sequencing confirmed the in-frame fusion. The breakpoint was located at the C-terminus of CSF3R, suggesting a pattern of truncation mutation of CSF3R. Unexpectedly, the patient failed to achieve a complete hematological response following the SRC kinase inhibitor dasatinib therapy, which has been reported to effectively inhibit truncated forms of CSF3R. The patient accepted allogeneic hematopoietic stem cell transplantation (HSCT) and currently remains in a good state. In conclusion, this report is the first to identify a fusion involving CSF3R and SPTAN1 in aCML with t(1;9)(p34;q34).