CBFB (Core-Binding Factor Subunit Beta 2)

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.

Our research identifies SPTAN1-kla as a novel oncogenic driver in HBV-related HCC, functioning via metabolic reprogramming and immune modulation. These findings position SPTAN1-kla as a promising therapeutic target for developing precision interventions against HBV-related HCC.

Combined inhibition of CDK12 and RUNX1 suppressed melanoma growth in vivo. These findings identify RUNX1/CBFβ as a compensatory mechanism in CDK12-inhibited melanoma and define a synthetic lethal interaction with translational potential for combinatorial therapy.

We developed a prognostic scoring system including clinical and molecular profiles termed NTCTH (NPM1 (HR=0.16), TP53 (HR=3.45), CBF t-AML (HR=0.09), first course intensive induction Therapy regime (HR=0.24), and allo-HSCT (HR=0.36)) in patients who performed NGS. Our study first demonstrated prognostic factors of t-AML in large samples from multiple centers in China and found that NPM1 and CBF t-AML were associated with superior OS, and TP53 was associated with inferior OS.

Patients harboring the CBFβ::MYH11 fusion gene showed significantly higher response rates to Ven-HMA induction than those with the RUNX1:: RUNX1T1 fusion gene (P<0.01) . Ven-HMA represents a novel therapeutic strategy that exhibits significant efficacy in inv (16) -positive patients; however, it demonstrates relatively lower remission rates in t (8; 21) -positive patients.

P2, N=178, Active, not recruiting, National Cancer Institute (NCI)

To provide evidence-based guidance on ALP, we conducted a retrospective analysis of 608 patients with newly diagnosed AML (non-M3), among whom 20 developed ALP during hydroxycarbamide (hydroxyurea) therapy and/or induction chemotherapy, resulting in an overall incidence rate of 3.3% (20/608) and a mortality rate of 35% (7/20)...Notably, CBFβ::MYH11 fusion positivity was associated with improved survival in ALP patients (p = 0.015). This study provides preliminary insights into the risk and prognostic factors of ALP.

Finally, we show that CBFβ-SMMHC could not induce leukemia in mice with a Runx1-R188Q mutation, which reduces RUNX1 DNA binding but not affecting its interaction with CBFβ-SMMHC or its sequestration to cytoplasm by CBFβ-SMMHC. Our data suggest that, in addition to binding RUNX1 to regulate gene expression, enhancing RUNX1 binding affinity to its target DNA is an important mechanism by which CBFβ-SMMHC contributes to leukemogenesis, highlighting RUNX1-DNA interaction as a potential therapeutic target in inv(16) AML.

Mutational analyses in breast cancer patients reveal frequent alterations in the DDR1-RUNX1 signaling axis, particularly co-occurring mutations. Together, these findings uncover DDR1-RUNX1 as a central signaling pathway driving breast epithelial differentiation, whose dysregulation may contribute fundamentally to breast cancer pathogenesis.