Identification of novel UBE2E3::PDE1A and CTC1::MEF2C fusion transcripts in acute myeloid leukemia

Acute myeloid leukemia (AML) is a hematologic malignancy caused by the malignant proliferation and differentiation block of immature myeloid cells (blasts) in the bone marrow. The pathogenesis, diagnostic classification, treatment, and prognosis of AML are fundamentally linked to the accumulation of genetic variants, fusion gene formation, and chromosomal karyotype abnormalities. Using mRNA sequencing (next-generation sequencing, NGS), we identified and validated two novel fusion genes, UBE2E3::PDE1A and CTC1::MEF2C, in a case of AML-M2a. This patient also harbored six single nucleotide variants (SNV) (EP300, KRAS, NRAS, RAD21, TET2, and TP53) and complex karyotype (CK). The chromosomes exhibited extreme instability and high variability, with tumor cells containing multiple clones and showing continuous karyotype evolution as the disease progressed. The patient was treated with three chemotherapy regimens (VMA, VHAA, and Decitabine-Venetoclax), but none achieved remission. We propose that the combination of these novel fusion genes, multiple SNVs, and the complex karyotype collectively contributed to the patient's multidrug resistance.