Despite the high rate of cure, resistant forms of childhood acute lymphoblastic leukemia (ALL) constitute a leading cause of cancer-related deaths in children. We propose to study childhood ALL patients in order to arrive at a better risk stratification, based on gene expression profiles measured in microarray studies which allow simultaneous testing of the expression levels of thousands of genes. The primary aim of the study is to characterise the profiles of relapsing and non-relapsing patients in order to identity features with prognostic value. This will be achieved by studying complementary sets of patient specimens banked at our own institution. The quality of this set of more than 130 patient specimens makes them particularly suited for microarray studies. They allow us to ask very specific questions. (1) Which genes are expressed in leukemia specimens from patients who will relapse because their disease is resistant to chemotherapy, while not expressed (or expressed at lower levels) in patients who will respond to therapy? (2) Which genes are expressed at low levels in specimens from relapsing patients? (3) Are the same genes differentially expressed in the leukemia cells at relapse, compared to the time of diagnosis? The answers to these three questions will provide the basis for the selection of a panel of suitable prognostic marker genes.
The aim of the project is to establish tests to measure expression levels of these candidate prognostic markers by realtime quantitative polymerase chain reaction (PCR). These will subsequently be studied in a separate cohort of patients who have received uniform treatment to verify that they are indeed of prognostic significance. The overall goal is to develop a prognostic test to be used at the time of diagnosing a child with ALL to determine whether the patient is likely to be successfully treated on current therapy protocols or has a high risk of relapse, hence, should be receiving more intensive therapy.
| Cleaver, Amanda L; Beesley, Alex H; Firth, Martin J et al. (2010) Gene-based outcome prediction in multiple cohorts of pediatric T-cell acute lymphoblastic leukemia: a Children's Oncology Group study. Mol Cancer 9:105 |
