cytarabine

This multitargeted regimen addresses the biologic heterogeneity of MCL and permits flexible MRD-guided decisions on consolidation and maintenance. Trial Registration: ClinicalTrials.gov identifier: NCT04626791.

Here, we found that multiple lipid metabolism processes are aberrantly activated in Ara-C resistant AML cells, accompanied by upregulation of JAK-STAT3 signaling and key lipid metabolic regulators, notably SREBP1 and CPT2...Our findings highlight the critical role of STAT3-driven lipid metabolism reprogramming in chemoresistance. Furthermore, W1307 emerges as a promising therapeutic candidate to overcome chemoresistance in leukemia treatment.

P2, N=32, Active, not recruiting, Liping Dou

We conclude that KIT mutations, especially exon 17, confer a high-risk phenotype in otherwise favorable pediatric AML1::ETO AML. Our exploratory data suggest this may be associated with a chemoresistant profile, potentially driven by SOCS1-associated JAK-STAT dysregulation. These findings highlight the necessity of refined risk stratification based on KIT exon profiling and support targeting the SOCS1/JAK-STAT axis to overcome therapy resistance.

P2, N=120, Recruiting, Chinese PLA General Hospital | Trial primary completion date: Dec 2027 --> Sep 2027

pFAO blockade synergizes with chemotherapy drugs such as venetoclax and cytarabine, enabling exploitation of metabolic vulnerabilities to improve therapeutic outcomes. Integrating solid tumor and leukemia insights, peroxisomes emerge as dynamic lipid-processing organelles coupling FAO, redox buffering, and inter-organelle exchange to cancer persistence. Targeting peroxisome-mediated lipid delivery offers a frontier for overcoming metabolic resilience and therapeutic resistance in leukemia.

As an exploratory analysis, subtype-specific therapeutic vulnerabilities were revealed: Subtype A displays predicted sensitivity to immune checkpoint inhibitors (anti-PD-1) and tipifarnib, whereas Subtype B responds better to cytarabine/doxorubicin. Crucially, experimental validation confirmed significant upregulation of key model genes (HIP1, SQLE, VNN1) in AML patient samples and cell lines (P < 0.05), reinforcing the model's biological relevance. These findings establish PCD dysregulation as a central axis of AML heterogeneity, providing a framework for precision risk stratification and hypothesis-generating immunophenotype-guided therapy.

ORR was 57%, 20% and 25% in patients treated by intensive chemotherapy (IC), hypomethylating agents (HMA) and BSC (including low intensity treatments as hydroxyurea and low-dose cytarabine), respectively. We observed poor outcome using IC or HMA encouraging us to propose new clinical trials in this specific subgroup. Only ASCT was able to improve prognosis.

Furthermore, USP30 enhanced Ara-C resistance in AML cells in vivo. Together, USP30 promoted Ara-C resistance in AML by deubiquitinating and stabilizing FOXM1, thereby enhancing tumor growth and cell survival.

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

P1, N=24, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2026 --> Jun 2027 | Trial primary completion date: Jun 2026 --> Jun 2027

P2, N=32, Not yet recruiting, Institute of Hematology & Blood Diseases Hospital, China