The molecular pathogenesis of acute myeloid leukemia.

The description of the molecular pathogenesis of acute myeloid leukemias (AML) has seen dramatic progress over the last years. Two major types of genetic events have been described that are crucial for leukemic transformation: alterations in myeloid transcription factors governing hematopoietic differentiation and activating mutations of signal transduction intermediates. These processes are highly interdependent, since the molecular events changing the transcriptional control in hematopoietic progenitor cells modify the composition of signal transduction molecules available for growth factor receptors, while the activating mutations in signal transduction molecules induce alterations in the activity and expression of several transcription factors that are crucial for normal myeloid differentiation. The purpose of this article is to review the current literature describing these genetic events, their biological consequences and their clinical implications. As the article will show, the recent description of several critical transforming mutations in AML may soon give rise to more efficient and less toxic molecularly targeted therapies of this deadly disease.