Acute myeloid leukemia remains a common blood cancer in adults, especially after age 60. Despite intense treatments, many patients relapse a few months after apparent remission. A team from Lille has just identified a molecule on the surface of cancer cells which could become a target to limit these relapses.
Carried out by Inserm, the University and the Lille University Hospital, this work shows that this molecule is present in large quantities on the cells causing the disease, called leukemic stem cells. This is the CD81 protein, the role of which has just been detailed in the review Signal Transduction and Targeted Therapy. A track that is still poorly known.
Why the CD81 protein is intriguing in acute myeloid leukemia
This form of leukemia is most common in adults. In the bone marrow, immature cells called blasts invade the space and block the production of blood cells. Despite chemotherapy, a population of leukemic stem cells remains lurking, capable of surviving treatments and then relaunching the disease.
The researchers analyzed 252 patient samples at diagnosis and 38 at the time of relapse. When CD81 is very present on the surface of blasts, the response to treatment is less good. Between diagnosis and relapse, its expression increases further, which directly links the protein to the risk of recurrence.
CD81, driver of aggression via leukemic stem cells
In the laboratory, the team modified the quantity of CD81, a membrane protein, on the surface of the blasts. When its level increases, the cells are more resistant to chemotherapy and their membrane becomes covered with extensions, signs of increased infiltration potential. In mice with AML, overexpression of CD81 is accompanied by a higher leukemic burden in blood and bone marrow.
When the expression of the protein decreases, the leukemic burden and the aggressiveness of the disease decline in the animal. By studying patient samples, the team showed that the proportion of leukemia stem cells highly rich in CD81 increases between diagnosis and relapse, and is linked to increased relapse risk and shorter overall survival. “Our work shows that the CD81 protein can be considered as a new marker of leukemic stem cells. As these cells manage to escape chemotherapy, targeting them via this CD81 protein could represent an effective therapeutic strategy, in addition to existing treatments.“, explains Meyling Cheok, Inserm research director and head of the study.
An anti-CD81 antibody which opens a therapeutic avenue to be confirmed
The researchers tested an antibody against CD81 on healthy bone marrow cells, with no toxicity observed at therapeutic doses. In mice carrying AML, this treatment, tolerated in combination with chemotherapy, reduced tumor burden, made the disease less aggressive, delayed relapse and prolonged survival. “If these results are confirmed, targeting CD81 could prove effective not only against persistent leukemia cells, but also as a second-line treatment in cases of relapse.“, concludes Meyling Cheok.