B-Cell Precursor Abnormalities in Childhood Acute Lymphoblastic Leukemia

Abstract

Despite the improvement in prognosis of childhood acute lymphoblastic leukemia (ALL) due to the implementation of relapse risk stratification, the majoritiy of relapses occurs in cases that were initially not considered as high-risk. Furthermore, current therapies are designed in the fifties and sixties of the past century and result toxicity. Therfore, there is a need for better relapse risk stratification and newly designed drugs that specifcally target leukemic cells. This thesis identifies the interaction and independency of different recently introduced relapse risk markers. It demonstrates that both BCR-ABL1-like gene expression signature and all variants of IKZF1 deletions are correlated to an unfavorable prognosis in B-cell precursor ALL (BCP-ALL). These observations resulted in the implementation of IKZF1 deletions in the currect DCOG ALL-11 treatment protocol. Furthermore, this thesis demonstrates that TCF3-rearranged BCP-ALL is characterized by an activated pre B-cell receptor. This pathway may be used for targetting leukemic cells in future clinical trials.