Chronic Myeloid Leukaemia Therapeutics

‌Chronic myeloid leukaemia (CML) is a relatively common adulthood leukaemia that is characterised by an acquired chromosomal abnormality. We have shown that a population of quiescent stem cells exists in CML that, by virtue of their dormancy, are resistant to conventional cell cycle-dependent chemotherapy drugs making CML an incurable disease in the absence of a bone marrow transplant (BMT). However, by studying quiescent leukaemic stem cells, it is hoped to reveal what factors maintain the cells in a quiescent state in order that a protocol may be developed to induce these cells to enter the cell cycle and thus be eradicated with chemotherapy.

It is becoming evident that imatinib mesylate (IM) is unlikely to completely eliminate primary CML stem cells in vitro and in vivo. We have shown pulsing with growth factor to initiate cell cycling prior to introducing IM significantly improves stem cell kill with respect to IM alone in vitro which has been translated into a clinical trial protocol. In order to further inform clinical trial design, pre-clinical testing in appropriate models of second-generation drugs, or novel ways of combining current drugs, is a major research focus. Moreover, as CML stem cell persistence in the bone marrow may be a drug delivery problem innovative ways of targeting the cancer stem cell, and not just the molecular cause of malignancy (BcrAbl in CML), is of particular interest.