Improving the outlook for children with Philadelphia positive ALL

Defects in genes that control blood cell development are common causes of blood cancers, such as acute lymphoblastic leukaemia. One well-recognised example involves a switch of genes between two chromosomes to produce an abnormal chromosome called the Philadelphia chromosome. This single genetic change can produce at least two types of leukaemia - chronic myeloid leukaemia (CML) and Philadelphia positive acute lymphoblastic leukaemia (Ph+ALL).

These two leukaemias are usually thought of as very distinct diseases and have different treatments. However, new scientific research indicates that some (but not all) cases of Ph+ALL share a lot in common with CML. Ph+ALL cases with CML-like features (called CML-like Ph+ALL) appear to be a new sub-type of leukaemia and may need different treatment approaches to enable long-term cure.

In this project, we will investigate this newly discovered leukaemia sub-type– CML-like Ph+ALL. We have three experimental aims:

1. To discover whether CML and CML-like Ph+ALL originate in the same types of primitive blood cells located in the bone marrow. This will help us understand how CML-like Ph+ALL develops.
2. To measure the levels of gene expression in the different leukaemia subtypes to see if we can identify a genetic “signature” that allows us to distinguish between Ph+ALL, CML and CML-like Ph+ALL. This will help devise new tests to use in the clinic to identify patients with CML-like Ph+ALL at the time of diagnosis.
3. To test CML-like Ph+ALL cells in the laboratory to see if they will respond to new less toxic therapies that our research team have recently developed to increase long-term cure for patients with CML.

In this way, we aim to improve the outlook for patients diagnosed with Ph+ALL, by making sure they get the right diagnosis and treatment.