Relapse of acute lymphoblastic leukemia in children in the context of microarray analyses

Over the last four decades the treatment of patients with newly diagnosed childhood acute lymphoblastic leukemia (ALL) has improved remarkably. However, still about 20% of children with ALL relapse despite risk-adapted polychemotherapy. The prognosis of relapsed ALL is relatively poor, even with modern aggressive chemotherapy. Identification of the biological and genetic mechanisms contributing to recurrence in patients with ALL is critical for the development of effective therapeutic strategies to treat refractory leukemic patients. Allogeneic hematopoietic stem-cell transplantation is the treatment of choice for many children with relapsed ALL. The gene expression profile obtained by microarray technology could provide important determinants of the drug response and clinical outcome in childhood ALL. Incorporation of the data on expression levels of newly identified genes into existing strategies of risk stratification might improve clinical management. Current microarray data show correlation of in vitro drug resistance with significant patterns of gene expression and explain clinical differences between early and late relapse. Genes involved in cell proliferation, self-renewal and differentiation, protein biosynthesis, carbohydrate metabolism, and DNA replication and repair are usually among those highly expressed in relapsed lymphoblasts. Current status and future perspectives of microarray data on gene expression and drug resistance profile in relapsed pediatric ALL are discussed in this review.