Blood cancer: When drugs work

New marker found for the treatment of leukaemia patients

Patients suffering from acute myeloid leukaemia (AML) – a certain form of blood cancer – are treated with the help of chemotherapy. Often, the active substances Decitabine and Azacitidine – so-called DNA methyltransferase inhibitors – are used for older patients because those affected cannot tolerate intensive chemotherapy. But only some of the AML patients respond to this treatment. However, it is not yet possible to estimate which patients will benefit from these agents and which will not before starting therapy.

Supposedly equivalent drugs: important difference found

Recently, a multidisciplinary international team with cooperation partners from Germany, the USA and Great Britain carried out a study on this problem, which was funded by the Frankfurt Foundation for Children with Cancer and the association Hilfe für krebskranke Kinder Frankfurt. The scientists were able to show that the enzyme SAMHD1 converts the activated form of Decitabine back into its inactive initial form. This prevents therapeutic activity.

Interestingly, the effect of Azacitidine is not influenced by SAMHD1. The results, published under the title “Selective inactivation of hypomethylating agents by SAMHD1 provides a rationale for therapeutic stratification in AML” in the renowned journal Nature Communications, show that there are significant differences between these drugs, which are often considered equivalent. Furthermore, the amount of SAMHD1 in AML cells as a marker could predict how sensitive they are to Decitabine. This is of potential clinical importance.

Frankfurt scientist in international research team

The research was led by Prof. Jindrich Cinatl from the University Hospital Frankfurt and Prof. Oliver Keppler from the Ludwig-Maximilians-University Munich. Numerous research groups from the Goethe University Frankfurt as well as scientists from the universities of Göttingen, Greifswald, Munich, Münster, Cambridge and Kent in Great Britain and Yale/USA were involved. The first author of the study, Prof. Thomas Oellerich from Goethe University, said of the results: “There is now justified hope that patients will benefit from these new research results in the foreseeable future.” Prof Oellerich holds a professorship of the German Consortium for Translational Cancer Research. Together with the University of Mainz, the University Hospital is a site of this health centre, which is funded by the Federal Ministry of Education and Research.

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