Leukemia accounts for more than one third of all childhood cancer cases—acute forms being the most frequent. In these forms, the cancer cells originate in immature and abnormal precursors of white blood cells, which proliferate chaotically without completing maturation, causing the cells to be unable to fulfil their functions. They fill up the space in the bone marrow and undermine the production and differentiation of other blood cells. A team from the François-Jacob Institute has focused on childhood acute lymphoblastic leukemia, an acute form of leukemia affecting T lymphocytes. Their work has highlighted the importance of an epigenetic factor.

"We are trying to understand what causes the blockage in the development of T lympocytes" said Irina Naguibneva, biologist at the François-Jacob Institute. "We are wondering why certain proteins necessary for their development are either insufficient or ineffective," she said. The researchers decided to take a closer look at microRNAs, which are small epigenetic factors that have a great influence on the production of proteins. "Certain microRNAs target messenger RNAs, the large RNAs that generate proteins from genes," Naguibneva added. "We have shown that a specific microRNA is directly related to the presence of protein TLX3, known for its implications in T-cell acute lymphoblastic leukemias."

In collaboration with hematologists, biologists and clinicians at the Trousseau Hospital, the researchers have analyzed the expression of more than 700 micro-RNAs in 41 young patients. They have found that a family of microRNA, including miR-125b which is known for its role in other cancers and is deregulated in one group of these T-leukemias. This family is characterized by the abnormal expression of protein TLX3. So is miR-125b also involved in this type of leukemia? "Our functional analysis shows a direct correlation between the expression of miR-125b and that of TLX3," Naguibneva said. "Whether in vitro or in vivo, the overexpression of TLX3, inducing the blockage of T-cell development, is associated with miR-125b induction." This correlation could allow researchers to explain some of the mechanisms of the TLX3 protein and miR-125b may be a good candidate to diagnose this disease.