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.