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Gene mutations affect the chances of being cured of leukaemia

Scientists at the University Hospital of Ulm and the Hanover Medical School (MHH) have succeeded in deciphering genetic defects in patients suffering from acute myeloid leukaemia. Their findings enable predictions to be made on the chances of the patient being cured of leukaemia and allow for more individualised therapies in the future.

Acute myeloid leukaemia (AML) is the most common form of acute leukaemia in adults. For quite some time, chromosomal alterations have been regarded as the predictive markers for a patient’s response to chemotherapy and on the prospects of a cure. However, fifty per cent of all AML patient samples do not reveal any chromosomal changes under the light microscope and are classified as AML with a normal karyotype.

Clinical consequences of genetic defects

Portrait of professor doctor Konstanze Döhner
Lead authors of the study: Prof. Dr. Konstanze Döhner
Portrait of doctor Richard Schlenk
and Dr. Richard Schlenk (Photo: University Hospital Ulm)
Over the last few years, scientists all over the world, including researchers in Ulm and Hanover, Germany, have succeeded in deciphering genetic defects in AML patients and assessing their clinical significance. Researchers at the Department of Haematology, Oncology, Rheumatology and Infectious Diseases at the University Hospital in Ulm and scientists of the Department of Haematology, Haemostaseology and Oncology at the Hanover Medical School made important contributions to improvements in this field.

In a recent study published in the New England Journal of Medicine, which was carried out by the German-Austrian AML Study Group (AMLSG) and coordinated by researchers from Ulm and Hanover, involved more than 40 centres in Germany and Austria. Over 800 patients with AML and normal karyotype were examined for genetic mutations, including the genes NPM1, FLT3, CEBPA, MLL and RAS.

Knowledge of the mutation enables prognoses to be made

The researchers found that specific genetic mutations or the combination of different mutations can be used as predictive markers on how patients respond to chemotherapy and the risk of recurrence and chances of a cure. The researchers also found that patients with genetic alterations with an unfavourable prognosis stand to have greater chances of cure following allogeneic bone marrow or blood stem cell transplantation. In contrast, patients with genetic alterations that suggest a positive prognosis, do not benefit from this intensive type of treatment and can be spared from unnecessary transplant-related morbidity.

According to information provided by the University Hospital in Ulm, the results of the study are likely to have a considerable effect on the treatment of AML patients. The researchers base this assumption on the fact that the WHO’s AML classification takes into consideration the genotypes identified in the study.
Dr. Richard F. Schlenk, chief physician and head of the AMLSG Study Centre, and Prof. Dr. Konstanze Döhner, chief physician and head of the Laboratory of Cytogenetic and Molecular Diagnostics at the University of Ulm, are the lead authors of the paper. According to information from the University Hospital of Ulm, the study was financed with grants from the German Federal Ministry of Education and Research (BMBF – Acute and Chronic Leukaemias Competence Centre) and IPD-Meta-Analysis: A model-based hierarchical prognostic system for adult patients with AML, as well as from the German José Carreras Leukaemia Foundation, the Else Kröner Fresenius Foundation and the Wilhelm Sander Foundation.
The results of the study were published on the 1st May 2008 in the renowned scientific journal New England Journal of Medicine.
Original publication: "Gene Mutations and Outcome of Treatment in Cytogenetically Normal Acute Myeloid Leukemia” – Studie zur prognostischen Bedeutung von Genmutationen bei der akuten myeloischen Leukämie (N Engl J Med 358:1909-18, 2008).

Source: University of Ulm 30th April 2008 (N, wp, 27.05.08)
Website address: https://www.gesundheitsindustrie-bw.de/en/article/press-release/gene-mutations-affect-the-chances-of-being-cured-of-leukaemia