Leukemia

P1, N=15, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Aug 2026 --> Dec 2026 | Trial primary completion date: Aug 2026 --> Dec 2026

The patient was treated with cytoreductive therapy, followed by imatinib, with a favorable clinical and hematologic response. This case highlights the potential for massive splenomegaly to mask CML and emphasizes the importance of early molecular testing. Splenectomy may unmask underlying hematologic malignancy through significant postoperative hematologic changes.

The enhanced cytotoxicity in leukemia cells was driven by oxidative stress: the general antioxidant N-acetylcysteine (NAC) and the mitochondrial ROS scavenger MitoTEMPO substantially reversed the combination effect. DNA damage markers (γH2AX and 8-OHdG) were also increased in MOLT-4 cells and attenuated by NAC and MitoTEMPO. Overall, cisplatin/PLB triggers selective and oxidative stress-dependent in leukemia cells while sparing normal macrophages, supporting the combination as a promising antileukemic approach with limited toxicity.

P1/2, N=70, Recruiting, Ellipses Pharma | Trial completion date: Dec 2026 --> Dec 2027 | Trial primary completion date: Oct 2025 --> Dec 2027

P=N/A, N=37, Active, not recruiting, University Hospital, Montpellier | Not yet recruiting --> Active, not recruiting

P=N/A, N=18, Active, not recruiting, Atılım University

T cell-redirecting therapies represent a central pillar in modern oncology, delivering high response rates across hematologic malignancies with expanding roles in earlier treatment settings. Future progress will depend on improving durability, optimizing sequencing, mitigating toxicity, and enhancing real-world deliverability through next-generation and multitarget platforms.

This study identifies WNK1 as a key oncogenic driver in AML and establishes WNK1 inhibition as a promising therapeutic strategy that not only suppresses AML progression but also sensitizes leukemia cells to venetoclax. These findings provide a rationale for novel combination regimens to overcome drug resistance in AML.

SF3B1 mutation enhances U1-U3 binding and increases the association of the U1-U3 complex with caRNA, driving chromatin-accessibility remolding, R-loop formation, DNA damage, and copy-number abnormalities that promote tumorigenesis. A U1-specific 2'-O-methoxyethyl antisense oligonucleotide that selectively blocks U1-U3 pairing suppresses these genomic abnormalities, reduces leukemic infiltration, and prolongs survival in xenograft and patient-derived models, establishing pathological snRNA-snoRNA rewiring as a critical driver of SF3B1-mutant leukemogenesis.

Integrated RNA-seq, CUT&TAG, and ATAC-seq analyses further showed that transcriptional changes induced by MLL3 loss were more closely associated with promoter-proximal alterations in H3K27Ac, H3K27me3, and chromatin accessibility than with putative MLL3-dependent enhancer regions. Together, these findings reveal that MLL3 suppresses breast tumor initiation through a dosage-sensitive, catalytic-independent adaptor function that regulates promoter-proximal epigenetic states.

Additionally, mir-155-5p demonstrated a significant decrease in the LIF-treated group compared to the PBS group (p < 0.0001). These results suggest that LIF modulates critical molecular pathways in RPL by influencing the expression of essential genes and miRNAs, highlighting its potential as a therapeutic target for pregnancy-related complications.

Future research should focus on clarifying the molecular mechanisms involved and conducting large-scale, population-based studies to validate these associations. Understanding these genetic variants may improve leukemia risk assessment and inform personalized therapeutic strategies.