Blast phase of chronic myeloid leukemia with concurrent BCR::ABL1 and SET::NUP214: A report of two cases

Abstract

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm defined by the presence of t(9;22)(q34;q11.2)/BCR::ABL1. Additional chromosomal abnormalities play an important role in the progression to CML. However, the additional fusion gene was rarely reported such as CBFB::MYH11. In this report, we described two cases of the co-occurrence of BCR::ABL1 and SET::NUP214 in CML-BP for the first time, which is associated with poor outcomes during tyrosine kinase inhibitor (TKI) treatment. Meanwhile, we retrospectively analyzed SET::NUP214 fusion transcript of the two cases at initial diagnosis of the CML chronic phase by quantitative RT-PCR, and detected at a ratio of 1.63% and 1.50%, respectively. SET::NUP214 may promote disease progression during the transformation of CML. This study highlights the importance of extended molecular testing at the initial diagnosis of CML-CP at TKI resistance and/or disease transformation.

The Incidence of Multiple Fusions in a Series of Pediatric Soft Tissue and Bone Tumors

“…This phenomenon has been reported in hematopoietic and epithelial malignancies and is thought to contribute to treatment resistance and disease progression. 9 , 10 , 11 , 15 , 24 While this is an intriguing possibility, the current study is constrained by limited clinical data. Further work on this cohort is continuing to determine the potential clinical and prognostic significance of multiple fusions in PSTBTs.…”

“… 6 Conversely, there remains continued debate about which fusion genes are of clinical value and are considered actionable, particularly when more than 1 fusion is discovered in a single tumor sample. 7 , 8 Several studies have demonstrated multiple fusions in single tumor samples, predominantly in hematopoietic 9 - 11 and epithelial 12 - 15 malignancies. While similar findings have been reported in soft tissue samples, 16 the incidence of multiple fusions in single PSTBT samples has not been well documented.…”

“… 16 However, some tumors have multiple fusions with therapeutic relevance. 11 - 13 Thus, the classification of fusions according to potential clinical significance is of paramount importance. There is a well-known scheme for classifying and reporting sequence variants in cancer, including SNVs, CNVs, and structural variants, based on criteria published by the American Society of Clinical Oncology and College of American Pathologists.…”

SET-CAN/NUP214 fusion gene in leukemia: general features and clinical advances

“…Chen Y et al. ( 5 ) first reported two rare cases of SET-CAN/NUP214 fusion gene positive CML in 2022 (No.18-19), the two patients detected BCR-ABL1 and SET-CAN/NUP214 fusion transcripts after 7 and 2 years of treatment with tyrosine kinase inhibitor (TKI), one patient (no.18) received chemotherapy and HSCT, and still survived up to the end of follow-up (95.7 months after initial diagnosis, 6.5 months after transplantation), the other patient (No.19) gave up treatment and died 36 months after the initial diagnosis. Retrospective analysis of samples from two patients showed that SET-CAN/NUP214 fusion transcript was present at the initial diagnosis, but not during TKI treatment.…”

“…Additional chromosome abnormalities play an important role in the deterioration of CML in chronic phase (CP) and accelerated phase (AP), SET-CAN/NUP214 fusion gene may be used as the main clone in CML to promote disease transformation, and its combination with BCR-ABL1 accelerates disease progression. Similar to the treatment of other fusion genes in CML cases, high intensity TKI chemotherapy and HSCT may be more effective for these patients ( 5 , 66 ).…”