RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1)

Our findings suggest that non-D816 KIT mutations are associated with a less aggressive clinical phenotype, lower mast-cell differentiation, and improved outcomes. These results support a biologically distinct role of non-D816 KIT variants in MNs and highlight the need for refined risk stratification incorporating KIT variant classes.

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

Collectively, these results demonstrate that N-WASP is suppressed in AML and is closely associated with disease risk and clinical outcome. N-WASP may serve as a novel prognostic biomarker and potential therapeutic target warranting further investigation.

However, there is growing literature that patterns of co-mutation, and more importantly, postremission measurable residual disease (MRD) status, modify these risks dynamically; necessitating an adaptive approach to optimize patient outcomes. In this review, we summarize evidence on how molecular and MRD features could assist clinicians in identifying high-risk patients within these favorable-risk subgroups, and where escalation of therapy, including with allogeneic transplantation in first remission, may be beneficial.

The conditioning regimen included olaparib, FLAG, busulfan, and cyclophosphamide. These findings highlight the potential of PARPi-enhanced conditioning to overcome chemotherapy resistance and reduce relapse by targeting leukemia stem cells (LSCs) through immune-mediated mechanisms. Small-sample retrospective studies have inherent limitations; hence further prospective studies are warranted to validate these results.

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.