Considering autophagy, ?-Catenin and E-Cadherin as innovative therapy aspects in AML

29.10.2015

Kühn K, Römer W

Cell Death Dis. 2015;6:e1950.

Cell Death Dis.            online article

Acute myeloid leukemia (AML) is the most common type of leukemia and characterized by a massive accumulation of immature and non-functional myeloid precursor cells in the blood and the bone marrow. A large number of these AML cases involve chromosomal translocations that generate chimeric oncoproteins like AML1-ETO or PML-RAR?, which stimulate abnormal proliferation and block myeloid differentiation. As classical chemotherapeutics only tend to highly proliferating cells and do not address at all the issue of differentiation arrest, a better understanding of these cytogenetic aberrations would facilitate the development of targeted therapies. Recently, impressive therapeutic successes have been achieved in acute promyelocytic leukemia (APL) exhibiting striking remission rates and long-term survival up to 90%. In this, the PML-RAR? fusion protein represses the transcription of genes, which are important for myeloid differentiation. The degradation of PML-RAR? can be induced by pharmacological doses of all-trans retinoic acid (ATRA), thereby enabling transcription and terminal differentiation of immature precursor cells. However, ATRA is only clinically successful for the small subset of APL patients. Thus, substances that may contribute to the differentiation of other AML subtypes and their modes of action are currently investigated. In a recently published issue of Cell Death Discovery, Kühn et al. describe the lectin LecB as inducer of the differentiation of the AML cell line THP-1 and propose a regulation by the interplay between autophagy and ?-Catenin.