A previously unknown subgroup of high-risk leukaemia in children has been revealed with a new, more accurate DNA test.

Our researchers, with collaborators in Prague, have found a new technique for tracking leukaemia cells containing a genetic change called BCR-ABL1. The findings were announced in a research paper published online last week in the journal Blood.

First, here’s some background. The commonest childhood cancer is Acute Lymphoblastic Leukaemia (ALL) which in turn has more than 20 subtypes, depending on which genes are altered. Overall, in Australia, more than 85% of children with ALL can be cured but patients with high-risk subtypes including BCR-ABL1 have a survival rate of less than 70%, despite the use of more intensive treatment.

The most common cause of treatment failure is disease relapse due to small numbers of cancer cells (Minimal Residual Disease or MRD) that survive throughout treatment. To determine each child’s risk of relapse, our MRD group carries out very sensitive DNA tests, specifically designed for each patient, using their bone marrow cells. The MRD results are provided to clinicians to allow them to adjust the child’s treatment if need be.

The MRD group is constantly looking to improve this disease monitoring with more accurate and reliable tests. This gene looks to be a good one to test for. Here’s why.

More accurate testing for residual disease

This new DNA test proved to be more accurate than standard MRD testing for patients with BCR-ABL-positive leukaemia. What’s more, the test revealed a biological diversity amongst this high-risk subgroup. In about 20% of children with this gene change, their leukaemia cells resembled chronic myeloid leukaemia (CML), the most common leukaemia in adults.

This is surprising but important, because treatment choices for CML can differ to those for ALL. Knowing which children are part of this subgroup will allow clinicians to make better decisions about treatments to maximise effectiveness and minimise side effects. Current treatment options for BCR-ABL-positive leukaemia include drugs targeted directly at BCR-ABL1, chemotherapy and bone marrow transplantation.

Rosemary Sutton
A/Prof Rosemary Sutton

A/Prof Rosemary Sutton is head of our MRD group, and one of the paper’s authors. She says that while the number of children with this newly-identified type of leukaemia is low, she is enthusiastic about the implications of this study for their treatment.

“I’m most excited about our capacity to do our MRD testing in a new and different way to benefit children with BCR-ABL-positive leukaemia, particularly this CML-like subtype of ALL.

“Now that we can test for the BCR-ABL1 gene directly, it will help identify the best treatment options for children in this high-risk group,” she said.

In Australia, the research was funded by grants from the National Health and Medical Research Council (NHMRC) and Cancer Council NSW.

Read the research findings in the recently published paper ‘Monitoring of childhood ALL using BCR-ABL1 genomic breakpoints identifies a subgroup with CML-like biology’  and learn more about this new test.

Top image: Jodie Giles (left) and Nicola Venn (right), research paper co-authors, look at DNA test results in the MRD lab.



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