V Foundation Awards $1 Million Grant to CU Anschutz for Infant ALL Research Targeting Menin Inhibition
核心洞察
A $1 million V Foundation grant will fund University of Colorado research into new treatments for infant acute lymphoblastic leukemia (搜索), a high-risk leukemia with very poor prognosis.
The "bedside to bench" study pairs clinical trial data from Kelly Faulk, MD, with cellular analysis by Patricia Ernst, PhD, using single-cell sequencing of patient bone marrow samples.
Researchers aim to understand why some patients respond to menin inhibitor (搜索) plus chemotherapy combinations while others do not, and to identify resistance mechanisms.
A $1 million grant from the V Foundation for Cancer Research (搜索) will support University of Colorado Anschutz Cancer Center (搜索) researcher Patricia Ernst, PhD, in her investigation of new treatment approaches for infant acute lymphoblastic leukemia (搜索) (ALL), an exceptionally high-risk form of leukemia that carries a very poor prognosis even with the advent of modern immunotherapy and cellular therapies.
The grant funds what the V Foundation terms "bedside to bench" research — a collaboration between Ernst, who serves as Molecular and Cellular Oncology program co-leader at the cancer center, and Kelly Faulk, MD, a physician-researcher at CU Anschutz Cancer Center and Children's Hospital Colorado. Faulk is overseeing an international clinical trial evaluating whether a menin inhibitor (搜索) combined with chemotherapy can effectively treat patients with infant ALL that has either relapsed after treatment or proven refractory to initial therapy.
Menin (搜索) inhibitors represent a targeted therapeutic class that works by blocking a protein leukemia cells require for survival. Early studies of these agents, conducted primarily in adults, demonstrated promising results with few side effects, culminating in the FDA approval of revumenib in 2024. However, as Ernst noted, "some patients did not respond or later became resistant."
Single-Cell Sequencing to Decode Treatment Response
A central component of the funded research involves Ernst's detailed cellular analysis of patient samples obtained through Faulk's clinical trial. Using single-cell sequencing to examine the entire transcriptome, the team will collect bone marrow aspirates at multiple time points: baseline (day 0, prior to the new drug), day 4, day 8, and day 29 of treatment.
"We want to know, does it look better? What changed? What happened to the cell?" Ernst explained. "We're working on the hypothesis that the drug is useful, but it may have flaws and Achilles' heels."
This longitudinal sampling strategy is designed to reveal the dynamic cellular changes occurring during menin inhibitor (搜索) therapy and to identify molecular signatures that distinguish responders from non-responders.
From Bench Findings to Animal Model Validation
The second phase of the research translates discoveries from patient samples into testable hypotheses in animal models. When the team identifies a gene that appears downregulated in responding patients, they plan to knock out that gene in animal models to determine whether it plays a deterministic role in treatment response.
Similarly, if the single-cell data suggest that immune cells are "struggling and partially succeeding in killing the leukemia," Ernst's team will explore ways to enhance that immune activity through modulation of known immune pathways. The broader aim is to uncover rational combination strategies — potentially involving other FDA-approved agents — that could improve the efficacy of menin inhibitor (搜索)-based regimens.
"Our goal is to develop better treatments for infants and young children with this aggressive leukemia, who currently have limited options," Ernst said. "This grant will help with that. It's encouraging, and it allows us to keep the trial going and keep accepting samples. I'm very grateful that private funding is still robust and people still believe in scientists."
The V Foundation for Cancer Research (搜索), founded in 1993 by ESPN and legendary basketball coach Jim Valvano, continues to fund high-impact oncology research through its grant programs, with this award specifically targeting the translational gap between clinical observation and mechanistic understanding in pediatric leukemia.