28 June 2013

A potential drug candidate identified by Japanese researchers who used x-ray crystallography at the AS could help to improve outcomes for sufferers of acute myeloid leukaemia. 

Acute myeloid leukaemia (AML) is a type of cancer that affects the blood and bone marrow. Overproduction of immature white blood cells stops the bone marrow making normal blood cells. The immature white cells cannot fight infection, and the shortage of red cells and platelets leads to anaemia and easy bleeding or bruising. (Leukaemia Foundation)

Leukaemia stem cells that survive conventional chemotherapy are thought to contribute to disease relapse, leading to poor long-term outcomes for AML patients.

The researchers used large-scale chemical library screening techniques to identify a pyrrolo-pyrimidine molecule (called RK-20449) with potential for binding to their chosen target, hematopoietic cell kinase (HCK), which is highly expressed in leukaemia stem cells. Crystal structures determined on the MX beamline revealed that RK-20449 binds to the activation pocket of HCK, confirming its potential for further investigation. Separate studies in laboratory mice showed that RK-20449 reduced the number of leukaemia stem cells. If RK-20449 can eliminate significant numbers of chemotherapy-resistant leukaemia stem cells, it may help prevent relapse and lead to improved outcomes for AML patients.

Yoriko Saito et al., A Pyrrolo-Pyrimidine Derivative Targets Human Primary AML Stem Cells in Vivo, Sci Transl Med, Vol. 5, Issue 181, p. 181ra52