Articles

Novel molecular insights and targeted therapies in T-cell acute lymphoblastic leukaemia

BJH - volume 8, issue 6, october 2017

S. Peirs PhD

SUMMARY

Patients with T-cell acute lymphoblastic leukaemia are mainly treated with intensive combination chemotherapy. Although this treatment strategy is quite successful in children, refractory or relapsed disease is more difficult to treat. Moreover, the chemotherapeutic agents are associated with substantial toxicity. In order to find more effective and less toxic therapies, the genetic and epigenetic alterations in T-cell acute lymphoblastic leukaemia are studied and molecularly targeted drugs are being developed. In this thesis, two new strategies to treat T-cell acute lymphoblastic leukaemia were identified and evaluated. On the one hand, high expression of the anti-apoptotic factor BCL2 was found as a hallmark of the immature T-cell acute lymphoblastic leukaemia subgroup. The BCL-2 specific inhibitor venetoclax proved to be a promising potential new therapy in T-cell acute lymphoblastic leukaemia and synergized with standard chemotherapeutic agents and BET bromodomain inhibitors. On the other hand, the enzyme KDM1A was identified as an interaction partner of the oncogenic transcription factor ZEB2. Antileukemic effects were demonstrated in several T-cell acute lymphoblastic leukaemia cell lines upon pharmacological inhibition of KDM1A.

(BELG J HEMATOL 2017;8(6):244–6)

Read more
X