BJH - volume 13, issue 8, december 2022
Q. Van Thillo MD, PhD
T-cell acute lymphoblastic leukaemia (T-ALL) is a devastating disease, which mainly occurs in childhood. Despite an improvement of the overall survival, the current treatments have many side effects, and patients with relapsed or refractory disease continue to have a very poor prognosis. T-ALL arises from T-cell progenitors that have acquired multiple genomic lesions, which co-operate to drive leukaemia development. For some genetic alterations, such as the TCF7::SPI1 fusion or ectopic expression of TLX3, their role in driving leukaemia remains largely unknown. Therefore, we first investigated the co-operation between TCF7::SPI1 and NRAS(G12D). Using a mouse model, we were able to show that β-catenin is a crucial coactivator for the oncogenic function of the TCF7::SPI1 fusion protein. In the second part, we demonstrated that TLX3 and FLT3-ITD co-operate in driving leukaemia by activating the SPI1/PU.1 transcriptional program in an ex vivo pro-T-cell model and mouse model. This oncogenic function of TLX3 was shown to be dependent on other cofactors. Together, these two models of oncogenic co-operation in T-ALL demonstrate that the interaction between oncogenic transcription factors and cofactors is paramount for their function. Thus, these data provide a rationale for developing treatments directed at these protein interactions in the future for leukaemia.
(BELG J HEMATOL 2022;13(8):325–7)
Read more
Top
To provide the best experiences, we and our partners use technologies like cookies to store and/or access device information. Consenting to these technologies will allow us and our partners to process personal data such as browsing behavior or unique IDs on this site and show (non-) personalized ads. Not consenting or withdrawing consent, may adversely affect certain features and functions.
Click below to consent to the above or make granular choices. Your choices will be applied to this site only. You can change your settings at any time, including withdrawing your consent, by using the toggles on the Cookie Policy, or by clicking on the manage consent button at the bottom of the screen.
