Higher levels of the protein UHRF1 were associated with shorter survival among adults with adult T-cell leukemia/lymphoma (ATLL), according to a study by Ying Lin and co-authors published in PLOS ONE on November 11, 2026. The researchers also found that reducing UHRF1 slowed growth and increased cell death in two ATLL cell lines in laboratory experiments. The results point to UHRF1 as a possible prognostic marker, but do not establish a clinical test or treatment.
The study examined tumor tissue from 72 people with ATLL and tissue from 30 people with reactive lymphadenopathy as controls. Using immunohistochemistry to measure UHRF1 protein, the authors reported higher signal in the ATLL samples: the median optical-density measure was 26.6, compared with 1.3 in controls. The median percentage of tissue area positive for UHRF1 was 9.9% in ATLL samples and 0.6% in controls. Both differences were statistically significant.
The researchers then compared outcomes in patients with higher and lower UHRF1 expression. After adjusting for clinical and laboratory characteristics, high expression remained associated with poorer progression-free survival and overall survival. The adjusted hazard ratios were 1.959 for progression-free survival and 2.397 for overall survival. These estimates describe associations in this study cohort; they do not show that UHRF1 itself caused the outcomes. The paper also reports a median follow-up of 10.5 months, limiting what the cohort can say about longer-term outcomes.
Higher UHRF1 expression was also associated with several signs of more aggressive disease, including acute or lymphoma-type ATLL, bone marrow involvement, and higher measures such as LDH, β2-microglobulin, and Ki-67. These patterns add context to the survival association, but they do not establish how UHRF1 relates to disease progression. The authors note that ATLL prognosis is currently assessed largely through clinical staging, and propose UHRF1 as a candidate molecular marker for further study.
To explore possible biological effects, the team reduced UHRF1 in two ATLL cell lines, HuT-102 and MT-4, using short-hairpin RNA. The modified cells grew more slowly than control cells. Measures of apoptosis, or programmed cell death, also increased in both lines, though the pattern differed between them. These experiments offer preliminary evidence about cell behavior in laboratory models. They do not show that targeting UHRF1 would help patients, and the authors call for validation in additional cell models, primary cells, and animal studies.
The team also investigated whether UHRF1 might act through the AMPK signaling pathway. They did not detect a stable interaction between UHRF1 and AMPK or the PP2A catalytic subunit PPP2CA, and reducing UHRF1 did not produce a clear change in measured AMPK-related proteins. The authors say the possible connection remains unresolved; weak and variable blot signals also prevented robust quantification of some measurements. The study therefore does not establish the mechanism behind the cell-growth and apoptosis findings.
The authors describe the patient analysis as retrospective and relatively small, and say the prognostic association needs testing in larger, multi-center cohorts. There is an inconsistency in the paper's description: the methods name Ningde Municipal Hospital and Fujian Medical University Union Hospital as sources of patients, while the limitations section calls the analysis single-center. The report does not explain this discrepancy. The authors also state that the underlying patient data are not publicly available because of restrictions.