American Association for Cancer Research

Identification and Targeting of Novel Rearrangements in High-risk ALL


Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, and the leading cause of nontraumatic death in children and young adults. Until recently, the reasons why some people respond poorly to treatment have not been understood. Mullighan’s recent preliminary studies have used new genetic techniques to analyze leukemic cells obtained from children with ALL at high risk of relapse. This has identified new genetic changes that are associated with treatment failure, including alterations of the gene IKZF1, and previously unidentified chromosomal changes that activate genes that drive proliferation of leukemic cells. These altered genes include ABL1, CRLF2, JAK2, and PDGFRB. These genes may be targeted by specific drugs, suggesting that patients with these alterations may be treated with these agents. This project will determine the nature and frequency of these novel genetic alterations in ALL in children and young adults, and will use cutting-edge genomic profiling approaches to identify new genetic alterations in high-risk ALL. Mullighan will go on to develop experimental models that mimic human ALL in order to determine how these changes cause leukemia, in order to enable testing of new targeted therapies.


Charles G. Mullighan, M.D., is assistant member in the department of pathology at St. Jude Children’s Research Hospital.

Updated: April 4, 2011