The characteristics and prognostic significance of the SET-CAN/NUP214 fusion gene in hematological malignancies: A systematic review

Abstract

Background: The SET-CAN/NUP214 fusion gene resulting from chromosomal del(9)(q34.11q34.13) or t(9;9) (q34;q34) has been found in T-cell acute lymphoblastic leukemia (T-ALL), B-cell acute lymphoblastic leukemia (B-ALL), acute myeloid leukemia (AML) and myeloid sarcoma (MS). Furthermore, the SET-CAN/NUP214 fusion gene has been found in the T-ALL cell line LOUCY and the AML line MEGAL. The common features of these cases are insensitivity to chemotherapy and poor prognosis. We reviewed the characteristics and prognostic significance of the SET-CAN/NUP214 fusion gene in hematological malignancies.Methods: This systematic literature search was conducted using the PubMed, Web of Science, Embase, and Cochrane Library databases. With the inclusion and exclusion criteria, we summarized all of the papers and performed a statistical analyses.Results: In general, the SET-CAN/NUP214 fusion gene is very rare in adult acute leukemia, more frequently found in T-ALL than in other types of leukemia, and more often in males. Flow cytometry data indicated that the markers CD34, CD33, CD13, and CD7 were common in SET-CAN/NUP214 positive acute leukemia, including ALL. Fluorescence in situ hybridization and arrays are important methods for detecting the fusion gene in newly diagnosed patients and can detect chromosomal del(9)(q34) will be detected. The chromosomal karyotype may be normal or complex, and, in terms of survival analysis, transplantation results in a better prognosis than chemotherapy alone.Conclusions and implications of key findings: The presence of SET-CAN/NUP214 fusion gene may be a Minimal Residual Disease of early recurrence, and it might be a poor indicator of outcome.Limitations: The mechanism, clinical characteristics, therapy and prognosis of the SET-CAN/NUP214 fusion gene in hematological malignancies require further research.

NUP214 Rearrangements in Leukemia Patients: A Case Series From a Single Institution

“…The overall frequency of NUP214 rearrangements was 2.08%; notably, the frequency was significantly higher in T-ALL (23.53%) than in AML (1.64%). Previous studies have reported frequencies of 6% for SET::NUP214 [ 18 ] and up to 6% for NUP214::ABL1 in T-ALL cases [ 12 ]. Collectively, these figures amount to 12%, which is approximately half the frequency found in the present study.…”

“…Unlike in the other fusion proteins, the NUP214 portion in the NUP214-ABL1 fusion protein is incorporated into the NPC, thereby combining the ABL1 tyrosine kinases to ensure that they can cross-phosphorylate and thus activate each other [ 17 ]. Regardless of the NUP214 partner gene or disease type, a common characteristic of all NUP214 rearrangements is that they are associated with treatment resistance and poor prognosis [ 18 , 19 ]. However, numerous studies in mice have shown that NUP214 rearrangements alone are insufficient for or at least inefficient in leukemogenesis [ 17 , 20 - 22 ].…”

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

“…Based on the collected patient information, the highest WBC count was 604.4 × 10 9 /L (T-ALL) and this patient died 5 months after diagnosis. The median percentage of leukemic blasts in the bone marrow was high (82.0-97.0%), probably reflecting the high proliferation status of fusion gene positive patients ( 4 , 24 ).…”

“…There is a large difference in the age of patients at initial diagnosis, the youngest patient is only 8 years old (T-ALL), the oldest patient is 58 years old (T-ALL), the average age is 30.2 years old and the patients are distributed in all age groups ( 6 , 17 , 24 , 26 , 35 , 41 ). Relatively speaking, the probability of fusion gene positive in adult leukemia patients is higher ( 40 ).…”

“…This necessitates more precise disease classification and optimization of therapeutic regimens. Research shows that HSCT can improve the prognosis, the level of SET-CAN/NUP214 after transplantation can predict recurrence to a certain extent ( 23 ), new methods such as CAR-T may be effective for patients and further research is needed ( 24 ).…”