Secondary Mutational and Cytogenetic Alterations in Core Binding Factor – Acute Myeloid Leukemia (Cbf-Aml): A Systematic Review and Meta-Analysis Publisher Pubmed



A Javidan AMIN ; A Azarboo ALIREZA ; S Jalali SAYEH ; P Fallahtafti PARISA ; Y Azimi Shahrabi YEGANEH ; M Yaghmaie MARJAN ; At Fathi Amir T
Source: Critical Reviews in Oncology/Hematology Published:2025

Abstract

Background: Acute myeloid leukemia (AML) with core-binding factor alterations (CBF-AML) is a notable subtype characterized by specific genetic alterations and a relatively favorable prognosis. Despite this, a significant proportion of CBF-AML patients experience relapse, indicating the potential prognostic role of other co-present cytogenetic abnormalities and gene mutations. Methods: A comprehensive search of PubMed, Embase, Web of Science, and Scopus was conducted until April 2024. Studies evaluating the prognostic impact of secondary cytogenetic abnormalities and gene mutations in CBF-AML were included. Data extraction and quality assessment were independently performed by two reviewers. Statistical analysis was conducted using the “meta” package in R. Results: 59 studies met the inclusion criteria. Mutations in the c-kit gene were significantly associated with decreased overall survival (OS) and disease-free survival (DFS) at 1, 5, and 10-year intervals. Patients with high c-kit expression also showed poorer survival outcomes. The presence of FLT3-ITD mutations was also correlated with lower survival rates. N-RAS mutations were found to have a variable impact on prognosis, with some studies indicating a negative effect on OS and DFS, while others showed no significant impact. Certain secondary cytogenetic abnormalities, such as loss of sex chromosomes and trisomy 8, were found to negatively affect prognosis, while trisomy 22 was found to increase 5-year RFS. Conclusion: Secondary cytogenetic abnormalities and mutations, notably c-KIT and FLT3-ITD, were linked to poorer survival in CBF-AML. Trisomy 8 also worsened prognosis, while N-RAS mutations showed minimal impact. These findings highlight the value of genetic profiling for risk stratification and personalized therapy. Future research should explore targeted treatments for high-risk subgroups to improve outcomes and reduce relapse rates. © 2025 Elsevier B.V., All rights reserved.