City of Hope Advances Novel AML Therapies and Unveils Breakthrough Research at ASH 2025
Key Insights
City of Hope is presenting 105 sessions at the 2025 American Society of Hematology Annual Meeting, showcasing advances in blood cancer research, cellular therapies, and precision medicine.
The institution's phase 1 clinical trial of AOH1996, a novel inhibitor targeting cancer-associated proliferating cell nuclear antigen (caPCNA (search)), offers a promising approach to overcome chemotherapy resistance in acute myeloid leukemia patients.
Researchers have identified FTO (search) enzyme as a therapeutic target in AML, developing FP54 (search) inhibitor that demonstrates superior antitumor efficacy compared to older inhibitors in experimental models.
City of Hope, one of the largest cancer research and treatment organizations in the United States, is showcasing groundbreaking advances in blood cancer treatment and precision medicine at the 2025 American Society of Hematology (ASH) Annual Meeting. The institution will present findings across 105 sessions, highlighting innovative therapies that promise to transform outcomes for patients with aggressive hematologic malignancies.
Novel AML Therapy Targets Chemotherapy Resistance
At the forefront of City of Hope's research portfolio is an innovative phase 1 clinical trial evaluating AOH1996, a novel therapeutic agent targeting acute myeloid leukemia (AML). Developed by Dr. Linda Malkas' laboratory, AOH1996 functions as an inhibitor of cancer-associated proliferating cell nuclear antigen (caPCNA (search)), a protein instrumental in the growth and proliferation of leukemia cells.
The investigational drug operates through a compelling mechanism that selectively disrupts caPCNA (search), inducing DNA damage and metabolic alterations specific to malignant cells. This approach presents a potential solution to overcome chemotherapy resistance and disease relapse in AML patients. The oral and continuous administration of AOH1996 is designed to assess safety, optimal dosing, and preliminary efficacy, with potential for subsequent combination therapies employing standard regimens such as Azacitidine and Venetoclax.
Targeting RNA Modification in Leukemia
City of Hope scientists have identified an exciting therapeutic target within the protein translation machinery of AML cells. The enzyme fat mass and obesity-associated protein (FTO (search)) has been spotlighted as a regulator that removes methylation marks from RNA strands, thereby enhancing the biogenesis of ribosomes and fueling unchecked protein synthesis critical for leukemic cell survival.
Led by systems biology expert Dr. Jianjun Chen, the team developed FP54 (search), a next-generation inhibitor that effectively neutralizes FTO (search)'s demethylase activity. Experimental models reveal that FP54 exhibits superior antitumor efficacy compared to older inhibitors, reducing leukemic burden and prolonging survival in murine models. This research significantly augments the therapeutic arsenal against AML by targeting the post-transcriptional regulatory axis.
Biomarker Discovery for Secondary Cancer Risk
Another transformative study from City of Hope has uncovered a potential biomarker to predict the risk of secondary malignancies in survivors of hematopoietic cell transplantation (HCT). Investigators including Drs. June-Wha Rhee and Saro Armenian conducted a comprehensive retrospective analysis of nearly two thousand patients and discovered that the presence of clonal hematopoiesis (CH) increases the likelihood of developing non-hematologic cancers post-HCT.
This association extends the known implications of CH beyond blood cancer predisposition to a broader oncogenic risk profile, emphasizing the need for surveillance and potentially tailored interventions in this vulnerable population.
ASH 2025 Presentations Highlight Clinical Progress
City of Hope's extensive presence at ASH 2025 includes several high-impact oral presentations. Dr. Ibrahim Aldoss will present results from the PARADIGM study, a phase 2 randomized multi-center trial comparing azacitidine and venetoclax to conventional induction chemotherapy for newly diagnosed fit adults with AML. The presentation is scheduled for the plenary session on Sunday, December 7.
Additional presentations will cover advances in CAR T cell therapy, including CD19 (search)-CAR T cell therapy as definitive consolidation in older adults with B-cell acute lymphoblastic leukemia, and BAFFR (search)-CAR T cells demonstrating durable responses in relapsed/refractory B-cell lymphomas with prior CD19-directed therapy failure.
Substantial Research Investment Fuels Innovation
Underpinning these discoveries are substantial research awards fueling continued innovation. Drs. Jianjun Chen and Xiaolan Deng secured a $4.7 million grant from the National Cancer Institute to investigate RNA modification and its role in codon-biased translation in AML. Similarly, Drs. Rama Natarajan and Zhen Chen received $3.6 million to explore epigenetic mechanisms in diabetic microvascular disease.
"ASH is where the future of hematology takes shape," said Marcel van den Brink, M.D., Ph.D., City of Hope chief physician executive and president of City of Hope National Medical Center. "Our teams are proud to share discoveries that deepen scientific understanding and accelerate progress toward more effective, safer treatments for patients worldwide."
Advancing Precision Medicine Approaches
City of Hope's integrated research model seamlessly connects laboratory discoveries with clinical application, accelerating the development of precision treatments. The institution's multidisciplinary approach encompasses molecular biology, genomics, clinical trials, and health services research, creating a comprehensive platform for scientific advancement.
The emerging therapies and diagnostic tools show immense potential not only to improve survival rates for devastating cancers like AML but also to elucidate fundamental biological processes that underpin aging, cancer susceptibility, and therapeutic resistance. These advances promise to extend healthspan and revolutionize the management of life-threatening diseases through scientific rigor and visionary collaboration.