. Current risk classification systems for pediatric ALL rely on both clinical and genetic features, including the presence of specific high-risk translocations; however, the most common cytogenetically-detected translocations in pediatric ALL collectively account for only 15% of patients. As a result, the majority of patients are classified, and thus treated, according to relatively nonspecific clinical features, such as age and leukocyte count. The long-term objective of this project is to improve treatment outcome for pediatric ALL by developing a new molecular risk classification scheme. The TEL/AML1 fusion is the most common genetic lesion in pediatric ALL, occurring in 25% of patients.
The Specific Aim of this application is to determine the prognostic importance of TEL gene rearrangements by prospectively studying all ALL patients registered on Pediatric Oncology Group protocols. Briefly, Southern blot analysis will be performed on genomic DNA isolated from diagnostic bone marrow on all newly diagnosed patients to determine the status (rearranged or germline) of the TEL gene. A multivariate analysis will then be performed to determine the independent prognostic importance of TEL status. This research may lead to less intensive therapy for patients with TEL gene rearrangements and may also allow the identification of patients who are currently assigned to low-risk protocols based on age and leukocyte count, but who actually need more intensive therapy. A secondary objective of this application is to determine the impact of MLL gene rearrangements on the outcome of children greater than one year old with ALL. This goal will be achieved by comparing molecular assays with standard karyotyping for detection of MLL rearrangements and determining the clinical significance of MLL rearrangements in this age group. MLL status will be detained by Southern blot analysis and results will be correlated with outcome. Risk-classification of infants with ALL will also be improved by using molecular techniques to identify those infants with MLL rearrangements.
| Rubnitz, Jeffrey E; Wichlan, David; Devidas, Meenakshi et al. (2008) Prospective analysis of TEL gene rearrangements in childhood acute lymphoblastic leukemia: a Children's Oncology Group study. J Clin Oncol 26:2186-91 |
