Stopping drug resistant processes in T-cell acute lymphoblastic leukaemia

Relapsed T-cell acute lymphoblastic leukaemia, which has come back during or after treatment, often can’t be treated with steroids as they no longer have an effect. The key to curing patients with relapsed ALL lies in a better understanding of the behaviour of treatment resistant leukaemia cells. Research has shown that using a medicine called Dasatinib alongside usual treatment can overcome steroid resistance. This treatment has now been included into a new international treatment guide that aims to test whether addition of Dasatinib will improve treatment response and long term outcomes in patients.

The only way to select patients who would benefit from Dasatinib is currently a complicated petri dish test. This test is available in Switzerland, but not in the UK. Dr Frederik van Delft and his team at Newcastle University plan to develop an alternative test using existing technology called flow cytometry, which is a way to measure the physical and chemical properties of groups of cells. Using this, the researchers will measure the activity levels of a leukaemia cell process that is closely linked to whether Dasatinib works for that patient.  

In patients with a good response to steroid treatment, the steroid enters the leukaemia cell and activates a series of genes which kills the leukaemia cell. When the steroid was given with Dasatinib, there was a stronger gene activation. The researchers plan to investigate the way that Dasatinib changes does this, in order to develop new treatments against steroid resistance.

Alongside this, the research team will use another technique, called CyTOF, to analyse leukaemia cells. Dr Frederik van Delft hopes this will help them find other processes which are making the T-cell acute lymphoblastic leukaemia resistant to treatment.