Molecular Heterogeneity of Core Binding Factor Acute Myeloid Leukemia (CBF-AML): Implications for Prognosis and for Treatment

Background/Objectives: Core binding factor acute myeloid leukemia (CBF-AML) is a subtype of AML characterized by specific genetic rearrangements, RUNX1::RUNX1T1 and CBFB::MYH11, that disrupt the CBF complex, which is essential for normal blood cell development. Although CBF-AML is regarded as a favorable-risk AML, it remains a challenging disease with significant molecular heterogeneity and relapse rates around 40–50%. A better understanding of the molecular heterogeneity of CBF-AML and the development of induction regimens reducing the risk of relapse are required. Methods: A systematic search of the literature showed the development of studies aiming to define the genetic heterogeneity of CBF-AML and of clinical studies aiming to improve the outcomes of newly diagnosed or relapsed/refractory, fit and unfit patients. The aim of the present review is to critically analyze these studies. Results and Conclusions: Molecular studies have identified the presence of some genetic alterations, such as KIT or FLT3-ITD mutations that increase the risk of relapse. Incorporation of Gemtuzumab Ozogamicin (GO) into frontline induction chemotherapy improved the outcomes of fit CBF-AML patients. Treatments based on the BCL2 inhibitor Venetoclax have been developed for unfit CBF-AML patients and may improve their outcomes. Serial monitoring via quantitative polymerase chain reaction for the specific fusion transcripts (RUNX1::RUNX1T1 or CBFB::MYH11) allows to define the minimal residua disease (MRD) and is crucial to monitor the effectiveness of treatments and to optimize the therapeutic strategy. The monitoring of MRD is also fundamental to define optimal strategies for consolidation strategy post-HSCT. These studies have contributed to identify CBF-AML patients who are at high risk of relapse and have to proceed to HSCT.