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Discovery of novel gene mutations in leukemia patients opens up personalized therapy options

Date:
August 2, 2013
Source:
Helmholtz Zentrum Muenchen - German Research Centre for Environmental Health
Summary:
Specific mutations (N676K) in the FLT3 receptor can contribute to the development of acute myeloid leukemia. The FLT3 receptor regulates cell growth, while activating gene mutations promote the uncontrolled proliferation of white blood cells.

Protein structure of the FLT3 receptor.
Credit: © Blood

Specific mutations (N676K) in the FLT3 receptor can contribute to the development of acute myeloid leukemia. The FLT3 receptor regulates cell growth, while activating gene mutations promote the uncontrolled proliferation of white blood cells. These findings were reported in the specialist journal Blood by a group of scientists from the Helmholtz Zentrum Mόnchen and the Hospital of the Ludwig Maximilians University (LMU) in Munich as part of a clinical research collaboration with the German Cancer Consortium (DKTK). The results provide the basis for the development of new leukemia treatments using specific inhibitors, which block growth signals.

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Gene mutations often trigger cancer. These changes in the DNA mostly affect the regulators of cellular metabolism or cell growth, which cause cells to degenerate and proliferate rapidly. Many such gene mutations that cause leukemia have been identified.

In about one third of patients with acute myeloid leukemia (AML) the malignant cells have a mutation in the growth-regulating FLT3 receptor. As the team of scientists headed by Dr. Philipp Greif and Professor Karsten Spiekermann have now discovered, 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. Mutations affecting amino-acid position N676 have not been previously detected and may allow a new classification of this form of leukemia, which is characterized by extremely high white blood cell counts. "The FLT3 receptor mutations we have found in these leukemia patients provide a new basis for treating the disease," says Dr. Philipp Greif. "We already have FLT3 receptor inhibitors at hand, which we can now use to treat the affected patients."

The study was conducted by the clinical cooperative group "Pathogenesis of acute myeloid leukemia," a collaboration between the Helmholtz Zentrum Mόnchen (HMGU) and the Department of Internal Medicine 3 at the Hospital of the Ludwig Maximilians University (LMU). The project leader and last author, Dr. Philipp Greif, heads a team of young scientists funded by the German Cancer Consortium (DKTK) within the clinical cooperative group. Professor Wolfgang Hiddemann, who heads the group, stresses the importance of this interdisciplinary collaboration: "Our 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."


Story Source:

The above story is based on materials provided by Helmholtz Zentrum Muenchen - German Research Centre for Environmental Health. Note: Materials may be edited for content and length.


Journal Reference:

  1. S. Opatz, H. Polzer, T. Herold, N. P. Konstandin, B. Ksienzyk, E. Zellmeier, S. Vosberg, A. Graf, S. Krebs, H. Blum, K. P. Hopfner, P. M. Kakadia, S. Schneider, A. Dufour, J. Braess, M. C. Sauerland, W. E. Berdel, T. Buchner, B. J. Woermann, W. Hiddemann, K. Spiekermann, S. K. Bohlander, P. A. Greif. Exome sequencing identifies recurring FLT3 N676K mutations in core-binding factor leukemia. Blood, 2013; DOI: 10.1182/blood-2013-01-476473

Cite This Page:

Helmholtz Zentrum Muenchen - German Research Centre for Environmental Health. "Discovery of novel gene mutations in leukemia patients opens up personalized therapy options." ScienceDaily. ScienceDaily, 2 August 2013. <www.sciencedaily.com/releases/2013/08/130802101738.htm>.
Helmholtz Zentrum Muenchen - German Research Centre for Environmental Health. (2013, August 2). Discovery of novel gene mutations in leukemia patients opens up personalized therapy options. ScienceDaily. Retrieved November 25, 2014 from www.sciencedaily.com/releases/2013/08/130802101738.htm
Helmholtz Zentrum Muenchen - German Research Centre for Environmental Health. "Discovery of novel gene mutations in leukemia patients opens up personalized therapy options." ScienceDaily. www.sciencedaily.com/releases/2013/08/130802101738.htm (accessed November 25, 2014).

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