Dr. Willman's program will refine and confirm molecular profiles that address three important clinical issues in leukemia using specimens from patients entered on clinical trials. The first goal is to improve risk classification, outcome prediction and therapeutic response in pediatric and adult ALL. The investigators will also refine profiles that differentiate ALL patients who will relapse early vs. those who will relapse late. Dr. Willman has developed profiles that provide additional information and do not simply recapitulate the known genetic alterations in this patient population. The second goal is to refine profiles that more accurately diagnose AML and ALL in infants <1 year of age and that improve outcome prediction. They will also attempt to develop profiles that predict response to different therapeutic regimens. Third, the investigators will refine profiles that improve risk classification, outcome prediction and response to targeted therapies in childhood and adult AML. All three of these goals represent significant clinical problems where patients would benefit from improved molecular diagnostics.
Mullighan CG et al (2009a) Deletion of IKZF1 and prognosis in acute lymphoblastic leukemia. N Engl J Med 360: 470-480. PMID: 19129520
Mullighan CG et al (2009b) JAK mutations in high-risk childhood acute lymphoblastic leukemia. Proc Natl Acad Sci U S A 106: 9414-9418. PMID: 19470474
These two publications from the Willman SPECS project improve the classification of pediatric ALL into meaningful risk categories for assignment of therapy.
Pediatric Oncology: Gene-expression profiling is prognostic in ALL cases
Nature Reviews Clinical Oncology 7, 239 (May, 2010)
Cancer Research Highlights: More Gene Mutations Found in Childhood Leukemia
NCI Cancer Bulletin; May 5, 2009