Acute Myeloid Leukemia: Genetic Tests Should Improve the Therapy
Most forms of AML are due to a new combination of chromosome fragments. In one of the most frequent AML mutations, a piece of chromosome 8 breaks off and is erroneously attached to chromosome 21. Thus, on the molecular level a so-called fusion gene develops. It has parts of both AML1 and ETO genes, which normally function completely independently of each other. The fusion gene codes for a mutated protein, which can no longer fulfill its original function – the regulation of cell maturation. The mutation characterized as t(8;21) generally responds well to treatment.
Moreover, the disease process is also influenced by additional less drastic mutations. Their identification is necessary to permit a well-founded prognosis and thus to make the therapy decision. Dr. Susanne Schnittger and her team are analyzing the genetic mutation KITD816, which occurs in 1.5 percent of all AML cases, but in 12.5 percent of patients with a t(8;21)- translocation. This is a small mutation which affects the KIT gene and has been known for years to be associated with the development of AML.
”Within this group, KITD816 occurs first and foremost in patients whose healing process is poor – and that, although cancer patients with the t(8;21) mutation actually respond well to chemotherapy,” said Susanne Schnittger, explaining her research results. Under the auspices of the National Genome Research Network (NGFN) funded by the German Federal Ministry of Education and Research (BMBF), she and her Munich team investigated the genotypes of a total of 1940 AML patients for the KITD816 mutation in order to identify patients who respond less well to current therapy. In the meantime the pharma industry has developed a new agent (PKC412) for the therapy of AML and launched it on the market. Susanne Schnittger: “First results give rise to hope that AML patients with a KITD816 mutation can be helped with the new agent PKC412.” Clinical studies have already shown that PKC412 is effective against other forms of AML. Further tests shall now also check this alternative therapy for the KITD816 mutation.
