Acute Myeloid Leukemia: identification of a new targeted therapy approach

Acute myeloid leukemia (AML) is a hematologic malignancy that develops from hematopoietic stem cells. In physiology, these cells are capable of proliferating and differentiating into the different types of blood cells such as lymphoid and myeloid cells. In some cases, these hematopoietic stem cells undergo genetic alterations leading to the blockage of their differentiation and to an excess of proliferation. Nowadays, conventional treatments for AML (chemotherapy and marrow transplantation) fail in many patients or are contraindicated in others (age, comorbidities). Personalized treatments adapted to the gene alterations of each patient represent a promising therapeutic strategy in AML.

The work carried out by J. Decroocq et al (CARPEM team 11), published in the journal Leukemia, focused on RAS mutated AML. Using two pharmacological screening approaches on RAS-mutated AML cells, the authors identified MEK inhibitors (Trametinib) and pyrivinium pamoate, an anti-parasitic agent that leads to alterations of mitochondrial respiration in AML cells, as new therapeutic candidates. Interestingly, the combination of these 2 agents in mouse models allows an efficient inhibition of the propagation of RAS+ AML tumor cells, suggesting a synergistic effect of these 2 molecules. Thus, the use of pyrivinium pamoate or the development of a bioavailable derivative compound coupled with a MEK inhibitor appears to be a promising new therapeutic strategy opportunity for these subgroups of AML.

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