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Personalized Leukemia Therapy Appears within Reach

Specific mutations of the FLT3 receptor may contribute to the development of acute myeloid leukemia. The Flt3 receptor regulates cell growth; activating gene mutations promote uncontrolled proliferation of white blood cells. This finding of the clinical cooperation group “Pathogenesis of Acute Myeloid Leukemia” can be used to develop a therapy by means of specific inhibitors that inhibit the growth signal.

Cancer is caused by mutations in the genome due to different factors. The gene mutations mostly affect the regulators of cellular metabolism or cell growth. As a consequence, the cells undergo malignant transformation and proliferate in an uncontrolled manner. Many of such gene mutations have been identified in leukemia.
In about one third of patients with acute myeloid leukemia (AML) the malignant cells have a mutation in the growth-regulating receptor FLT3.

As the team of scientists headed by Dr. Philipp Greif and Professor Karsten Spiekermann have now discovered by means of exome sequencing, blood cancer cells from a substantial number of patients in a subgroup of AML (so-called core-binding factor leukemias) also carry mutations in this receptor. The gene alterations at position N676 were previously unknown and now allow a new classification of this leukemia form, which is characterized by a particularly high cell count. In addition, according to the researchers, the newly identified FLT3 receptor mutations in this leukemia group provide a new target for personalized treatment of the disease. Inhibitors of the FLT3 receptor are already available and can now be administered to the affected patients.

The study was conducted by the clinical cooperation group “Pathogenesis of Acute Myeloid Leukemia”, a joint institution of Helmholtz Zentrum München and the Department of Internal Medicine III at the University Hospital of Munich. The aim of the clinical cooperation group (CCG) is to identify leukemia-causing mutations and to investigate why certain mutations can cause leukemia.

The head of the CCG Wolfgang Hiddemann emphasizes the importance of this
interdisciplinary collaboration: The results show in an exemplary way how innovative research methods, such as high-throughput DNA sequencing, allow discoveries, even in structures that have already been thoroughly examined. These insights into the molecular basis of the disease open up new treatment options for patients.

Acute myeloid leukemia (AML) is the most common cancer of the hematopoietic system occurring in adults. Only about 25 to 30 percent of the patients survive the first five years after diagnosis.



The mutation N676K is a new target for the treatment of acute myeloid leukemia. Patients with this mutation can be identified by this marker, and the uncontrolled cell growth can be inhibited by inhibitors of the growth-regulating FLT3 receptor. Source: HMGU