Acute Myelogenous Leukemia

In vivo+, Que slowed SHI-1 xenograft growth and decreased expression of c-Myc, GLUT1, and HK2. This study demonstrates that Que exerts antileukemia effects by inhibiting proliferation, glycolysis, and energy metabolism in acute monocytic leukemia cells.

Model-agnostic explanations (Shapley additive explanations) consistently highlighted white blood cell count, age, transplantation, and TET2 among top contributors. An interpretable machine learning framework built from accessible clinical and genomic variables provided quantitative risk discrimination for IR-AML across development and external test cohorts, supporting individualized risk assessment and informing refinement of prognostic stratification.

Here, we describe a novel DHODH inhibitor, JNJ-74856665, that showed strong efficacy in a subset of AML samples. The transcriptional regulator SREBF2, known to control cholesterol and lipid metabolism, was upregulated in DHODHi sensitive AMLs, and a strong synergy was observed between combination of both DHODHi and the SREBP inhibitor dipyridamole. Our data indicate that combined DHODH and SREBP inhibition is of interest to explore further as a therapeutic target option in AML.

Venetoclax-based regimens represent a major advancement in the treatment of NPM1-mutated AML, promoting a shift toward more targeted and less toxic therapeutic approaches. Nonetheless, prospective randomized trials are required to establish standardized clinical algorithms and to refine maintenance and discontinuation strategies, with the ultimate goal of improving patient quality of life and long-term outcomes.

Each case also harbored co-occurring mutations associated with adverse prognosis, such as BCOR, ASXL1, and RUNX1. These findings suggest NUTM1 fusions in AML could represent a distinct molecular subset with potentially poor prognosis, warranting further functional and clinical investigation to clarify their biological and therapeutic significance.

Despite these gains, the absolute survival benefit remains modest, prolonged cytopenias are universal, and outcomes in TP53-mutated or younger adverse-risk patients are still poor, raising legitimate questions about cost-effectiveness and generalizability. Nonetheless, CPX-351 stands as the first clinically validated example of ratiometric nanomedicine in oncology, proving that reformulating established drugs can yield meaningful progress where novel agents have often failed.

P2, N=57, Completed, Sidney Kimmel Cancer Center at Thomas Jefferson University | Active, not recruiting --> Completed

P1, N=34, Active, not recruiting, City of Hope Medical Center | Trial completion date: Aug 2025 --> Jul 2026

P=N/A, N=120, Completed, AbbVie | Active, not recruiting --> Completed

P1, N=53, Suspended, National Cancer Institute (NCI) | Recruiting --> Suspended

This study suggests that ddPCR may be a transformative tool for MRD monitoring with the superior sensitivity and longer lead time for predicting relapse than conventional methods in AML/MDS patients after allo-HSCT. Its outstanding performance supports its integration into routine post-transplant monitoring to enable early intervention and improve outcomes.

We propose that such a low-intensity regimen may be suitable for older patients with AML, who are unfit for intensive chemotherapy. We also present data indicating that PRI5202 induces myeloid differentiation in blasts from patients with myelodysplastic syndrome (MDS), and we propose to further investigate PRI5202 as a differentiation therapy for patients suffering from MDS.