Evaluating the PHFScore Prognostic Tool in Acute Myeloid Leukemia
Acute myeloid leukemia (AML) patients face survival rates that vary widely due to the disease’s complex cellular heterogeneity. Publishing in this week’s journal Science Advances, researchers at the Centre for Genomic Regulation (CRG) in Barcelona introduced a six-gene scoring system called PHFScore, which combines the polycomb factor gene PHF19 with five other genomic markers to predict patient survival outcomes and chemotherapy response more accurately than single-marker analysis alone.
In Plain English: The Clinical Takeaway
- What it is: A new six-gene molecular panel (PHFScore) that groups AML patients by their genetic risk profile using standard bone marrow samples.
- Why it matters: It improves prognostic accuracy, helping clinicians identify high-risk patients who are less likely to achieve remission with standard chemotherapy.
- What’s next: The identified genes could serve as targets for future therapeutic drug development, though clinical implementation requires further validation.
Molecular Mechanisms and Cellular Plasticity in AML Survival
The journey toward the PHFScore began with a focus on a single genetic regulator, PHF19. As healthcare-in-europe.com reported, PHF19 belongs to a gene family that keeps other genes switched off during cellular differentiation—the biological process where immature cells mature into specialized blood cells. Earlier work from ICREA Research Professor Luciano Di Croce’s lab demonstrated that mice lacking PHF19 develop conditions resembling myelodysplastic syndrome, where precursor blood cells fail to mature properly.
To examine how leukaemia initiates in cells with similar starting defects, lead author Dr. Gianni Gamarra and his colleagues introduced a leukemia-causing gene into mouse blood cells with and without PHF19. Cells lacking the gene formed more colonies, took hold more easily upon transplantation, and stayed locked in an immature, stem-cell-like state. Blood cells form a hierarchy,
Gamarra explained as noted by News-Medical. At the top are stem cells, which are still plastic and could become almost anything. As they move down, they mature and take on a fixed identity. The more a cancer holds on to that plasticity, the more malignant it tends to be.
This cellular plasticity rendered the cells significantly harder to treat. Cells lacking PHF19 largely ignored chemotherapeutic drugs designed to force leukemia cells into a mature state. By bridging laboratory mouse models with human patient datasets, the CRG team identified six genes that behaved consistently across both systems. Genes including CARMIL1, HOPX, and ALDH1A1 displayed higher activity in patients with poor outcomes, while CALR, STAR, and PHF19 showed lower activity.
| Gene Marker Category | Specific Genes | Clinical Association |
|---|---|---|
| Upregulated Genes (Poor Prognosis) | CARMIL1, HOPX, ALDH1A1 | Associated with aggressive disease progression and lower survival rates |
| Downregulated Genes (Lower Activity) | CALR, STAR, PHF19 | Associated with loss of cellular differentiation and chemo-resistance |
Clinical Implications and Remission Rates in Younger Adults
The clinical stakes of this genomic profiling are stark, particularly when evaluating treatment efficacy in younger adults treated for AML. According to findings corroborated by News-Medical from the Science Advances study, patients with the lowest levels of PHF19 survived for significantly shorter durations than those with high levels. Furthermore, they exhibited dramatically lower rates of achieving remission after standard chemotherapy.
Fewer than half of patients with low PHF19 levels went into remission following standard therapy, compared to up to 85% of patients with the highest levels of the gene. Because patients already undergo bone marrow biopsies at initial diagnostic workups, measuring a targeted six-gene panel offers a simpler and more cost-effective prognostic route than sequencing broader genomic profiles. Some of these genes have never been previously linked to hematological malignancies, opening potential avenues for novel targeted therapies.
Contraindications & When to Consult a Doctor
While the PHFScore represents a significant advance in molecular pathology, it remains a research-stage prognostic instrument rather than an immediate diagnostic bedside test.
Future Trajectory and Research Support
The five-year study was spearheaded by Luciano Di Croce and Gianni Gamarra at the Centre for Genomic Regulation, incorporating single-cell expertise from Lars Velten’s group alongside technological support from the CRG’s Genomics Unit and Flow Cytometry Unit. As researchers continue to explore the exact mechanisms of these newly implicated genes, the PHFScore lays the groundwork for refined stratification models in clinical trials.
References
- Gamarra Figueroa, G. P., et al. (2026). Polycomb factor PHF19 affects AML initiation, patient prognosis, and survival. Science Advances. DOI: 10.1126/sciadv.aed6757
- Centre for Genomic Regulation (CRG) Research Releases. (2026). Six-gene scoring system could help predict AML survival.
- News-Medical. (2026). Six-gene score could improve survival predictions for acute myeloid leukemia.
