Acute myeloid leukemia: targeting the CD81 protein to prevent relapse

By Elodie Vaz | Published on April 28, 2026 | 3 min read


Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults, with incidence increasing after the age of 60. This hematologic malignancy is characterized by uncontrolled proliferation of immature cells—blasts—in the bone marrow and peripheral blood, disrupting normal hematopoiesis. Despite recent therapeutic advances, prognosis remains poor, largely due to a high rate of relapse. These treatment failures are mainly attributed to a rare subpopulation of leukemic stem cells (LSCs), which can evade conventional cytotoxic therapies and reinitiate the disease.  

In this context, a team from the Lille Interdisciplinary Cancer Research Center (Inserm/University of Lille/Lille University Hospital/CNRS) investigated the membrane protein CD81. Already known to be involved in interprotein communication within the cell membrane and overexpressed in certain cancers, this protein may play a key role in LSC biology. The aim of the study was to evaluate its relevance as both a prognostic biomarker and a therapeutic target in AML.

A protein at the heart of the problem

The researchers analyzed a cohort of 252 patient samples at diagnosis and 38 at relapse. CD81 expression on the surface of blasts was correlated with clinical data. In parallel, in vitro experimental models were used to modulate the protein’s expression in order to study its functional consequences. These observations were complemented by murine models of AML. Finally, advanced technology enabled the specific isolation of LSCs to closely analyze their CD81 expression profile.  

The analyses show that overexpression of CD81 is associated with poor therapeutic response. Its expression increases between diagnosis and relapse, suggesting a role in treatment resistance. Functionally, increased CD81 makes blasts more resistant to chemotherapy and is associated with morphological changes in the cell membrane that enhance their infiltration capacity. These findings are confirmed in vivo, where CD81 overexpression correlates with higher leukemic burden and increased tissue infiltration.

A promising target for future treatments

The study also highlights that LSCs overexpressing CD81 significantly increase at the time of relapse. This population is associated with a higher risk of relapse and shorter overall survival. “Our work shows that the CD81 protein can be considered a new marker of leukemic stem cells. Since these cells manage to escape chemotherapy, targeting them via CD81 could represent an effective therapeutic strategy, in addition to existing treatments,” explains Dr. Meyling Cheok in an Inserm press release.   From a therapeutic perspective, an anti-CD81 antibody was evaluated. It showed no toxicity on healthy cells in vitro, and in mice, its administration in combination with chemotherapy led to a sustained reduction in tumor burden, decreased disease aggressiveness, delayed relapse, and improved survival.  

These results position CD81 as both a prognostic biomarker and a potential therapeutic target in AML. Targeting LSCs via CD81 could help overcome one of the main therapeutic challenges—the persistence of resistant cells. “If these results are confirmed, targeting CD81 could prove effective not only against persistent leukemic cells, but also as a second-line treatment in cases of relapse,” concludes Meyling Cheok.


                  Read next: Pediatric leukemia: what if everything happens at the cell surface?



About the Author – Elodie Vaz
Health journalist, CFPJ graduate (2023).
Élodie explores the marks diseases leave on bodies and, more broadly, on human life. A registered nurse since 2010, she spent twelve years at patients’ bedsides before exchanging her stethoscope for a notebook. She now investigates the links between environment and health, convinced that the vitality of life cannot be reduced to that of humans alone.