Signaling landscape of AML: The story so far

Acute myeloid leukemia (AML) is the most frequent leukemia in adults and presents a very high incidence all over the world. The most important aberrations involve mutations and large chromosomal translocations in the genes responsible for hematopoiesis, resulting in an abnormal signal transduction activation that boosts survival and proliferation of progenitor cells and a typical accumulation of poorly differentiated myeloid cells. Acute myeloid leukemia is an extremely complex malignancy with considerable genetic, epigenetic, and phenotypic heterogeneity. Most AML genomes present very few mutations, which are responsible for the aberrant phenotypes observed. The possibility to characterize the mutations present in single cells and the studies on hematopoiesis performed both in vitro and in vivo, make AML an ideal model for investigating the underlying mechanisms of tumorigenesis. In the last years, the signaling proteins identified as specifically mutated in AML have raised huge consideration as attractive therapeutic targets and many efforts are currently ongoing in order to design ad hoc strategies to improve prognosis and therapy. Recent advances in the conventional treatments, together with innovative therapies, show significant promises for curing AML patients.