CBFB (Core-Binding Factor Subunit Beta 2)

We also highlight broader RUNX/CBFβ inhibitors, alternative therapeutic vulnerabilities linked to fusion-associated cofactors and chromatin regulators, and combination approaches such as BET bromodomain inhibition that enhance antileukemic activity. Together, these findings support the CBFβ-SMMHC-RUNX1 interface as a mechanistically informative and therapeutically actionable target, and illustrate the broader potential of targeting oncogenic transcription factor complexes in core-binding factor AML.

AKT inhibitors eliminated differences in DNMT3B, HIF1α, and MMP2 expression between normoxia and hypoxia. In hypoxic conditions, CBFβ-MYH11 regulates the AKT/DNMT3B/SHP2 pathway to modulate variations in P53 expression, ultimately hindering the progression of hepatocellular carcinoma.

Importantly, combining CBFβ-SMMHC inhibitors with BET bromodomain inhibitors synergistically eradicates inv(16) leukemia in preclinical models. Together, these insights into the structural basis and functional role of the CBFβ-SMMHC-RUNX1 interface highlight protein-protein interaction disruption as a promising translational strategy in core-binding factor leukemia therapy.

Runx1 restricts some forms of breast cancer and inhibits the full oncogenic potential of aberrant WNT signalling. Combined Runx1 and Runx2 loss dramatically accelerates disease progression suggesting that Runx2 can substitute for Runx1 in dampening the oncogenic effects of WNT signalling.

CBFB acts as a key player in Gastric cancer progression, with higher expression predicting poor prognosis and showing strong diagnostic potential. Mechanistically, CBFB may promote progression by engaging STAT3; single-cell data indicate overexpression in mast cells with enhanced mast cell-endothelial crosstalk. Functional data support CBFB as a therapeutic target in Gastric cancer.

Mechanistically, CBF-β loss leads to upregulation of type I interferon signalling, and we uncover a direct inhibitory role for CBF-β at the STING locus controlling Interferon Stimulated Gene expression. Targeting CBF-β in kidney cancer both selectively induces tumour cell lethality and promotes activation of type I interferon signalling.

The early use of VEN-AZA appears to be effective and well tolerated in AML patients with molecular relapse after allo-HSCT, particularly in those carrying CBFβ::MYH11 fusion gene or NPM1 mutation.

P2, N=178, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Feb 2026 --> Feb 2027

In RUNX1::RUNX1T1 patients, older age, elevated initial white blood cell count, lower hemoglobin, lower initial fusion transcript load, and the presence of FLT3-ITD or KIT D816/D822 mutations were associated with an increased likelihood of PC2 nonresponse. Based on these variables, we developed a weighted scoring system with good discrimination to identify RUNX1::RUNX1T1 patients at high risk of PC2 nonresponse.

Cytologic, flow cytometric, and molecular analyses of ascitic fluid can provide critical diagnostic evidence for myeloid sarcoma in cases where abdominal effusion is associated with myeloid sarcoma involvement.

This differential effect arose because different concentrations of IMU-935 were required to disrupt the interaction in Th17 cells versus thymocytes, due to varying levels of RUNX1 that compete with RORγt for CBFβ binding. This study reveals an unreported mechanism for RORγt regulation and a selective RORγt inhibitor that prevents Th17-driven autoimmunity without the risk of lethal lymphoma from thymocyte disruption.

KIT exon 17 mutational status and treatment protocol was identified as independent prognostic factors for OS and EFS in CBF-AML and RUNX1::RUNX1T1-AML. Our study found that prospective evaluation of KIT mutations is crucial in pediatric CBF-AML, particularly in RUNX1::RUNX1T1 patients, where the survival can be significantly improved by high-risk chemotherapy and hematopoietic stem cell transplantation.