Molecular pathogenesis and therapeutic strategies in CBF-AML

Abstract

Core-binding factor acute myeloid leukemia (CBF-AML), defined by t(8;21)(q22;q22)/RUNX1::RUNX1T1 or inv(16)(p13.1q22)/t(16;16)(p13.1;q22)/CBFB::MYH11, represents a distinct AML subset with characteristic biology. CBF-AML occurs more frequently in younger patients and is classified as a favorable-risk category in the current prognostic systems. Nevertheless, approximately 40% of the patients experience relapse, underscoring the need for improved therapeutic strategies. Recent comprehensive genomic analyses have demonstrated that co-occurring genetic alterations differ substantially between RUNX1::RUNX1T1-positive and CBFB::MYH11-positive cases, highlighting the heterogeneity within this subgroup. High-dose cytarabine (HD-AraC) consolidation remains the standard post-remission therapy, whereas the addition of gemtuzumab ozogamicin (GO) has shown benefits in reducing relapse risk. Furthermore, clinical trials are investigating tyrosine kinase inhibitors with KIT-inhibitory activity as potential therapeutic options. In parallel, measurable residual disease (MRD) monitoring using chimeric transcript quantification has been shown to provide valuable prognostic information and guide treatment stratification. The integration of genomic profiles and MRD dynamics into refined risk stratification frameworks is expected to optimize treatment decision-making. Future strategies incorporating molecularly targeted agents in combination with conventional chemotherapy may contribute to reducing relapse rates and further improving long-term survival in patients with CBF-AML.