P2/3, N=450, Enrolling by invitation, First Affiliated Hospital of Zhejiang University

P2/3, N=267, Enrolling by invitation, First Affiliated Hospital of Zhejiang University

c-Myc activation is a key driver of VEN resistance in t(8;21) AML. HHT acts as a mechanistically complementary agent, restoring VEN sensitivity. These results provide a preclinical rationale for clinical evaluation of VEN-HHT combination therapy in genetically defined AML subsets.

P2, N=46, Not yet recruiting, Dongguan People's Hospital

Bcl-2 homology domain 3 (BH3) mimetics, such as venetoclax (ABT-199), which targets BCL2, have shown promising activity in AML. Additionally, MIK665 showed significant activity against a subset of paediatric AML patient-derived xenografts (PDXs) in both ex vivo and in vivo experiments, with minimal impact on cardiac tissue pathophysiology. These findings strongly support the clinical advancement of MIK665 for paediatric AML treatment in a precision medicine approach.

Therefore, this platform is particularly suited for the treatment of FLT3-ITD AML while potentially applicable to other AML subtypes with high CD71 expression. By enabling specific intracellular accumulation of HHT and multitarget inhibition of FLT3 signaling pathways, this system achieves enhanced anti-AML efficacy both in vitro and in vivo, offering strong potential for future clinical translation.

The resulting nanoparticles were investigated in a refractory AML mouse model (AML1-ETO & C-KITD816V) with a high level of CXCR4 and in the t(8; 21)-positive AML cell line Kasumi-1. It was shown that E5-LNP@siAE effectively achieved RNAi of AML1-ETO and antagonism of CXCR4, thereby synergistically inducing effective multi-lineage differentiation, leading to significantly enhanced differentiation-post apoptotic responses of AML cells to homoharringtonine and remarkably prolonged survival in refractory AML mice.

Sabutoclax treatment was associated with both decreased protein expression and reduced nuclear translocation of NFATc1. Future studies could focus on comprehensive evaluation of its pharmacokinetic properties, systemic toxicity, and therapeutic efficacy in more clinically relevant metastatic models to establish its potential application in breast cancer-induced osteolytic bone destruction.

We previously conducted a prospective clinical trial on R/R AML with chemotherapy regimen BHA (bortezomib, homoharringtonine and cytarabine), which demonstrated promising efficacy in patients with FLT3-mutated R/R AML. Notably, this degradation effect was partially reversed by chloroquine. These findings demonstrate that bortezomib and homoharringtonine have synergistic effects and lead to degradation of FLT3-ITD oncoprotein, potentially contributing to a higher complete remission rate in FLT3-ITD R/R AML.

P2, N=41, Active, not recruiting, Institute of Hematology & Blood Diseases Hospital, China | Recruiting --> Active, not recruiting | N=60 --> 41 | Trial completion date: Jun 2027 --> Jun 2028 | Trial primary completion date: Jun 2026 --> Dec 2027

We report a case of a 42-year-old patient with EVI1-positive AML harboring the MLL-AF6 fusion gene, who failed to achieve remission after undergoing standard "IA" induction therapy and was then treated with VAH (venetoclax, azacitidine, and homoharringtonine) consolidation chemotherapy. This case suggests that the combination of ATRA with the VAH regimen may demonstrate promising efficacy and an acceptable safety profile in patients with EVI1-positive AML who are refractory to conventional chemotherapy. However, further clinical studies are required to confirm its wider applicability.