Last Updated: 11/21/12
Leukemia Signatures for Risk of Classification & Targeting
Cheryl L. Willman, M.D., Ph.D.
University of New Mexico
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.
Collaborators:
- The project includes investigators from the Fred Hutchinson Cancer Research Center, New York University and two clinical cooperative groups, COG and SWOG.
- The project is supported by a very strong informatics and statistical team at the University of New Mexico in collaboration with Sandia National Laboratory. Sandia investigators have developed a novel, powerful analytical algorithm, VxInsight. Biostatistical support is also provided by each of the collaborators and the cooperative groups.
Projects:
- Refine the prognostic gene expression signature for high risk pediatric ALL patients. Develop an RT-PCR assay for the ALL prognostic signature and validate the signature in an independent ALL patient population.
- Determine differences in gene expression signatures taken at diagnosis and at relapse in ALL patients who relapse early (<36 months) and late (>36 months).
- Develop a prognostic gene expression signature for high risk adult ALL patients. Develop an RT-PCR assay for the ALL prognostic signature and validate the signature in an independent ALL patient population.
- Refine and validate a prognostic signature for infant (<1 year) leukemia.
- Refine and validate prognostic signatures for adult and pediatric AML.
- Develop signatures that predict response to targeted therapies in adult and pediatric AML.
Featured Publications:
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.
See also:
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
