Grant: Project Grant

Acute Myeloid Leukemia or AML is an aggressive blood cancer that is fatal if not treated. AML regroups many different subtypes which can be distinguished by typical chromosomal aberrations which in some cases correlate with the prognosis of the disease. AML patients are for the most part still treated with chemotherapeutic regimens that have not changed since several decades. Treatment is toxic and the only cure is a stem cell transplantation, which is not only costly but also restricted to individuals with the ability to withstand the harsh preparations required for such a procedure. AML cells are rapidly dividing, immature cells and if it were possible to induce these cells to differentiate into non dividing mature cells, the leukemia could be stopped and eventually be cured. That this is indeed possible has been demonstrated for a subtype of AML, the acute promyelocytic leukemia. Here, the cells respond to a treatment with retinoic acid by differentiation to mature stages and arrest their cell division. Patients affected by this subtype tolerate the therapy with retinoic acid well and most can be cured. We now have evidence that AML cells from another type of leukemia that also affects children can be induced to differentiate and forced to stop growing by a particular RNA molecule called "ELDR". In contrast to the regular messenger RNAs, which represents the blueprint for the building of proteins in our body, ELDR has no such coding potential and belongs to the group of so-called "long non-coding RNA". These types of RNA molecules have regulatory functions for instance in the organisation of the genome. We also observed that ELDR amplifies the effect of retinoic acid and other drugs against AML, which suggests that this RNA has the potential fo a future therapeutic agent. We propose therefore to clarify how ELDR acts at a molecular level in AML cells and how its ability to drive differentiation of leukemic cells can be exploited for a new AML therapy.