23 November 2017
New insights into the molecular mechanisms of leukaemia
Published online 27 January 2017
Scientists unveil a promising therapeutic target for T-cell acute lymphoblastic leukaemia.
The functions of ZEB2 protein that are related to tumour development might be dependent on its interaction with KDM1A protein, according to a new study that probes the molecular mechanism of leukaemia.
ZEB2 drives the expression of multiple genes that are involved in inducing leukaemia and some of its cells’ aggressive features, such as self-renewal and metastasis. Until this research, however, there has been little understanding of this process on the molecular level.
The scientists from Australia, Belgium and Egypt are now suggesting that ZEB2 interacts with KDM1A, which has the ability to modify the histone proteins wrapped around the DNA, to promote the survival and self-renewal of T-cell acute lymphoblastic leukaemia (T-ALL).
Inhibiting KDM1A in ZEB2-overexpressing leukaemic cell lines consequently resulted in decreasing cell survival in comparison to ZEB2-deficient cell lines. More interestingly, inhibiting KDM1A in ZEB2-overexpressing transplanted T-ALL cells in mice delayed the tumour’s evolution as well as reduced the tumour burden.
“Further work needs to be done here to determine the role of this interaction in other forms of leukaemia including acute myeloid leukaemia (AML), and solid tumours, as well. Also, it would be significant to explore whether the KDM1A inhibition can be beneficial in these settings where ZEB2 expression is increased,” says co-author Jody Haigh from the Department of Clinical Hematology at Monash University in Australia.
“Our hope for the future is that studying the ZEB2–KDM1A interactions will lead to revealing novel drug targets and effective combination therapies to treat a wide range of cancers."
- Goossens S. et al. Oncogenic ZEB2 activation drives sensitivity towards KDM1A inhibition in T-cell acute lymphoblastic leukemia. Blood http://dx.doi.org/10.1182/blood-2016-06-721191 (2017).