(R)-2-Hydroxyglutarate: A Leukemic Enantiomer

(R)-2-Hydroxyglutarate: A Leukemic Enantiomer

Author: Melania Tesio

Acute myeloid leukemia (AML) is a blood cancer characterized by a hyper proliferation of white blood cells. Mutations in isocitrate dehydrogenases, enzymes converting isocitrate into α-ketoglutarate, often occur in AML patients. Their precise pathogenic role, however, remains elusive.

Julie-Aurore Losman, Dana-Farber Cancer Institute, Boston, USA, and colleagues revealed that the (R)-enantiomer of 2-hydroxyglutarate (HG, pictured) plays a crucial role in the development of the leukemic disease. The compound, abnormally produced by isocitrate dehydrogenases as a consequence of their mutations, accumulates in blood cells and deregulate their proliferation, thus promoting the leukemic transformation. (R)-2-HG effects are, however, reversible, as compounds blocking its production could restore a normal cellular growth. Thus, the pharmacological inhibition of (R)-2-HG production might be a valuable therapeutic intervention against acute myeloid leukemias.

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