P1/2, N=43, Suspended, SymBio Pharmaceuticals | Recruiting --> Suspended

Proteomic profiling showed that NAMPT inhibition with KPT-9274 induced adaptive upregulation of BCL2, an anti-apoptotic protein, highlighting a survival mechanism...Additionally, NAMPT inhibition reduced PARP activity and impaired DNA repair pathways, sensitizing AML cells to cytarabine and hypomethylating agents. Together, these results demonstrate that NAMPT inhibition both potentiates venetoclax activity and enhances the cytotoxic effects of standard chemotherapies by targeting metabolic and DNA repair vulnerabilities. These findings provide strong preclinical support for evaluating NAMPT and BCL2 dual inhibition strategies in future AML clinical trials.

Cytarabine (ara-C) and fludarabine (F-ara-A) are key drugs in leukaemia treatment. Mechanistically, IMPDHi depleted allosteric SAMHD1 activators GTP and dGTP, thereby increasing active triphosphate metabolites in SAMHD1-proficient, but not SAMHD1-deficient, cells. Our findings suggest that the addition of IMPDHi to ara-C and F-ara-A may have therapeutic benefits in some AML cases.

For relapsed and refractory APL, relevant drug resistance gene monitoring should be carried out. Some relapsed and refractory APL patients who do not respond to conventional treatment are at risk of death. We report a successful case, the regimen of VEN targeted therapy combined with chemotherapy still holds promise for the treatment of future relapsed/refractory APL.

Additionally, the study on an Fc-silenced mutant (GZ1 LALAPG) indicated that Fc-mediated functions played a critical role in the enhanced therapeutic effects. These findings highlighted the potential of anti-CD36 mAb in combination with Ara-C as a novel treatment strategy for overcoming drug resistance in AML.

To investigate this question, we used a knock-in mouse that constitutively expresses a Calr frameshift allele and introduced conditional Ezh2 deletion triggered by tamoxifen...Short-term colony assays showed that inhibition of PPARγ modestly increased the anti-proliferative effect of cytarabine on AML-derived stem and progenitor cells, suggesting a possible reliance on FAO...At a non-critical stage, peripheral counts remain near-normal while bone marrow HSPC compartments are already distorted. AML-like, but not sMF-like, Flk2- CD48+ LSK cells transmit leukemia and display enhanced fatty-acid-oxidation signatures, suggesting a distinct, potentially targetable metabolic bias.

P3, N=205, Terminated, Fred Hutchinson Cancer Center | N=500 --> 205 | Trial completion date: Aug 2027 --> Apr 2025 | Active, not recruiting --> Terminated; due to increased mortality and futility analyses

Infiltrative mediastinal/retroperitoneal MS may present with esophageal obstruction and mimic lymphoma or carcinoma. High-index suspicion, targeted biopsy with high-power morphology, and a focused immunohistochemical panel are critical for timely diagnosis and treatment initiation.

P1, N=10, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Oct 2025 --> Oct 2026

P3, N=99, Recruiting, The Affiliated People's Hospital of Ningbo University | Trial completion date: Dec 2026 --> Aug 2026 | Trial primary completion date: Dec 2026 --> Aug 2026

Sapacitabine with olaparib produces high rates of hematologic toxicity. However, the ORR of 50%, mPFS of 9.7 months, and durability of response in some patients suggest possible combinatorial benefit. Further exploration of olaparib with different sapacitabine schedules or substitution of a PARP1-selective inhibitor to potentially decrease hematological toxicity is warranted.

DDX6 KO leads to rapid PB dissolution and release of PB-enriched mRNAs, such as BCAT1, into the cytosol, where these transcripts undergo degradation. By reducing BCAT1 levels, DDX6 KO reprograms amino acid metabolism and sensitizes AML cells to cytarabine chemotherapy.