New treatment approach against leukemia

An international research team led by researchers from Vetmeduni Vienna have made an important discovery that could lead to a better understanding of lymphocytic leukemia. They identified the STAT5B protein as crucial for the development of the disease. The findings represent a possible therapeutic approach involving new, precision medicine strategies.

The BCR/ABL fusion gene, which does not occur among healthy people, has been shown to be a causative agent in the pathogenesis of B-cell acute lymphocytic leukemia (ALL). This gene leads to transformation of white blood cells, which can proliferate out of control. Earlier studies by the research group of Veronika Sexl at Vetmeduni Vienna showed that the STAT5 transcription factor was essential for the development of BCR/ABL-induced leukemia. Surprisingly, mutations in StatB, but not StatA, have been frequently described in hematopoietic tumors; therefore, the authors of this new study used BCR/ABL as a model system to disentangle the contribution of STAT5A or STAT5B for leukemogenesis. They found that the absence of STAT5A led to a decrease in cell survival and the formation of colonies of malignant cancer cells; the effects were even more drastic in the absence of STAT5B. In the mouse model, loss of STAT5B increased interferon response and suppressed transformation. The opposite scenario was true in patients with overactive STAT5B: the interferon response against tumour growth was suppressed and transformation was enhanced. According to the researchers, this may be of direct clinical relevance for patients, as a better understanding of the complex role of STAT5B could enable the development of precision medicine strategies to treat BCR/ABL ALL.

Published in Leukemia

Sebastian Kollmann, Eva Grundschober, Barbara Maurer, Wolfgang Warsch, Reinhard Grausenburger, Leo Edlinger, Jani Huuhtanen, Sabine Lagger, Lothar Hennighausen, Peter Valente, Thomas Decker, Birgit Strobl, Mathias Müller, Satu Mustjoki, Andrea Hölbl-Kovacic and Veronika Sexl.