Poor prognosis in acute lymphoblastic leukemia may relate to promoter hypermethylation of cancer-related genes.

The hallmark of acute lymphoblastic leukemia (ALL) is a progressive appearance of malignant cell behavior that is triggered by the evolution of altered gene function. ALL has traditionally been viewed as a genetic disease; however, epigenetic defects also play an important role. DNA promoter methylation has gained increasing recognition as an important mechanism for transcriptional silencing of tumor-suppressor genes. Hypermethylation may contribute to the pathogenesis of leukemias providing an alternative route to gene mutation. We have reported that gene methylation in ALL cells is the most important way to inactivate cancer-related genes in this disease. In fact, this epigenetic event can help to inactivate tumor-suppressive apoptotic or growth-arresting responses and has prognostic impact in B- and T-ALL. The presence in individual tumors of multiple genes simultaneously methylated is an independent factor of poor prognosis in both childhood and adult ALL in terms of disease-free survival and overall survival. Moreover, methylation status is able to redefine the prognosis of selected ALL groups with well-established prognostic features.