RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1)

P2, N=29, Active, not recruiting, Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias | Recruiting --> Active, not recruiting

Selective pharmacologic inhibition of HDAC3 or targeted gene silencing via lipid nanoparticles suppressed the growth of lineage-plastic cancer cells, uncovering a therapeutically actionable vulnerability. Together, these findings establish RUNX1T1 as a cross-lineage regulator of HOX code-defined plasticity and identify the RUNX1T1-HDAC axis as a targetable mechanism underlying cancer lineage plasticity.

These results were confirmed in the CBF-2006 validation cohort. KIT-TKD mutations in RUNX1::RUNX1T1 and FLT3-ITD in CBFB::MYH11 worsen prognosis independently of MRD and must be included in risk stratification of CBF AMLs.

The median overall survival was 35.1 months for AML with RUNX1::RUNX1T1 versus 24.0 months for other AML (p = 0.0797) and 28.1 months in patients with KIT mutations versus 25.6 months in those without (p = 0.9051). These data highlight a strong biological association between RUNX1::RUNX1T1 and KIT exon 17 mutations and underscore the need for prospectively designed studies and the evaluation of KIT-directed therapeutic strategies in this subset of patients with AML.

CK and KIT mutations jointly identify a high-risk subgroup within t(8;21) AML. This baseline genetic stratification provides a foundation for risk-adapted therapy, with MRD assessment at CR offering complementary prognostic information.

The presence of MS appeared to correlate with worse clinical outcomes, as 67% of patients with MS died, compared to none without. Our findings expand the recognized molecular diversity of MBNs and provide insights into their biological behaviors, underscoring the clinical significance of identifying potential prognostic factors.

All patients remained disease-free, with no events of measurable residual disease (MRD) positivity by flow cytometry or molecular analysis documented. These findings preliminarily confirm that venetoclax, cytarabine, and homoharringtonine-based cytoreductive therapy is a safe and effective bridging therapy for allo-HSCT in patients with refractory/relapsed AML and RUNX1::RUNX1T1 fusion gene.

Our preliminary data provides proof of principle to suggest that environmental factors associated with childhood leukaemia risk have the potential to induce chromosomal translocations. Whilst this study is not designed to estimate in vivo risk or translocation frequency, it has allowed us to demonstrate a biologically plausible mechanism for epidemiological associations. Understanding the risk factors contributing to leukaemia-initiating events will be essential to refine public health policy and tailor prevention strategies.

This study established internally validated 3-year OS and RFS nomograms for pediatric RUNX1::RUNX1T1-positive AML with excellent discrimination and clinical utility. Prospective multicenter validation is warranted to confirm the robustness and facilitate clinical adoption.

P2, N=162, Not yet recruiting, National Cancer Institute (NCI) | Initiation date: Feb 2026 --> Jun 2026

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.