GENOMIC PREDICTOR OF ACUTE LYMPHOCYTIC LEUKEMIA BIOLOGY

Dana-Farber Cancer Institute, Boston MA

Investigators

Linked publications & trials

Abstract

DESCRIPTION: (Applicant's Description) Despite overall improvements in the treatment of childhood ALL, the outcome of individual patients remains uncertain. Thus the individualization of treatment for patients with the intent of maximizing cure yet minimizing treatment-related side effects is not currently feasible. While particular chromosomal translocations do have prognostic value, most patients lack such informative rearrangements. Furthermore, the mechanism of action of these characteristic translocation proteins is in large part unknown, thereby limiting their ability to contribute to an overall, generalizable understanding of treatment response and outcome prediction. The goal of Project 8 is to take a genomic approach to these issues, focusing on gene expression profiling using DNA microarrays coupled with pattern recognition computer algorithms. Specifically, we will focus on 3 subgroups of ALL patients: 1) those who in general have a favorable outcome (namely, TEL/AML1 positive patients), 2) those with a generally unfavorable prognosis (infants and adults), and 3) T-cell ALL, for which response is unpredictable. By comparing the gene expression profiles of these groups of patients, we hope to identify gene expression 'signatures' of favorable and unfavorable prognosis. The development of improved molecular predictors of outcome is an essential first step in the targeting of specific therapies to specific patients. It is also anticipated that this project will result in new insights into the mechanism by which, for example, the TEL/AML1 fusion protein causes ALL that is highly curable. Such insights are likely to be valuable not only for understanding TEL/AML1-induced ALL, but also for understanding chemoresponsiveness in general.