Emerging treatments in acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL) is a clonal proliferation of early B- and T-lymphocyte progenitors and results in the accumulation of leukemic blasts in the bone marrow and various extramedullary sites. It affects both children and adults, with peak prevalence between the ages of 2 to 5 years. Despite current treatment protocols achieving rapid cytoreduction in the vast majority of patients, serious acute and late complications are frequent and resistance to chemotherapy often develops. In contrast to the successes obtained with pediatric patients, treatment outcomes for adults remain poor with only 40% of patients being long-term survivors. Extensive research in the field of ALL has helped understand the mechanisms that control leukemic cells, facilitating the design of new drugs that specifically interfere with leukemic pathways and overcome chemo-resistance induced by common treatment regimens. Herein, we review the current status of the development of novel anti-leukemic agents, with emphasis on small molecular inhibitors that have already translated into clinical trials and are in the advanced stages of preclinical development. Challenges to successful development of each strategy are discussed.