MOLECULAR TECHNOLOGIES FOR IMPROVED RISK CLASSIFICATION AND THERAPY FOR ACUTE LYMPHOBLASTIC LEUKEMIA IN CHILDREN AND ADULTS

摘要

To improve risk classification and outcome prediction in ALL, gene expression profiles were obtained using oligonucleotide arrays in a retrospective case control study of 220 children with B precursor ALL. Using multiple statistical methods and computational tools, these comprehensive gene expression profiles were reduced to a 26 gene expression classifier that was highly predictive of overall outcome. Each of these 26 genes was shown to provide additional prognositc information relative to established prognositc variables. The 26 genes include signaling, adhesion and growth regulatory proteins (RHoGEF4, FYB, HNK-I sulfotransferase, SMADl, HABP4, PHYH, IFI44L, JAGl, EFN-B2, type 3 inositol-1,4,5 triphosphate receptor, MONDOA, DOKl, CDK8, CD44, CL5/RANTES, galectin SPARC) and novel genes not previously known to play a role in hematopoiesis or leukemogenesis (DREBIN, MIDKINE, and the hypothetical protein LJ20154 or OPALlwhich have been cloned and characterized).