28 January 2019

Austrian researchers have announced new discoveries about genes that play a key role in the development of B-cell acute lymphocytic leukaemia.

The research team, based at Vetmeduni, Vienna, has been studying the STAT5 transcription factor, which is essential for the development of BCR/ABL-induced leukaemia.

STAT5 is coded for by two genes, STAT5A and STAT5B. It had previously been assumed that the two genes, which are 90% identical, were "functionally equal."

However, the two genes have different roles to play in the development of disease, according to their new findings published in the journal Leukaemia.

In mouse models, the team showed that removing Stat5b had the most significant effects, suppressing tumour transformation and increasing interferon response. However, removing Stat5a had less significant effects on leukaemia development or progression. Their work suggests that STAT5B is the more important gene for BCR/ABL-induced B-cell acute lymphocytic leukaemia.

Andrea Hölbl-Kovacic, who co-led the study, said: "Our data show that STAT5A and STAT5B are twins with different personalities, and that STAT5B facilitates leukaemogenesis in BCR/ABL leukaemia.

"Our findings might help explain the high frequency of STAT5B mutations in haematopoietic tumours."

Study co-leader Veronika Sexl said: "What is exciting is that in recent years cases have been found of patients with mutations that result in STAT5 activation and are assumed to drive disease. Surprisingly, these mutations were found at a much higher frequency in STAT5B than in STAT5A."

Source: Kollmann, S., Grundschober, E., Maurer, B., Warsch, W., Grausenburger, R., Edlinger, L., Huuhtanen, J., Lagger, S., Hennighausen, L., Valente, P., Decker, T., Strobl, B., Müller, M., Mustjoki, S., Hölbl-Kovacic, A., Sexl, V. (2019) “Twins with different personalities: STAT5B – but not STAT5A – has a key role in BCR/ABL-induced leukemia”, Leukemia, available at doi: 10.1038/s41375-018-0369-5


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