Pediatric acute lymphoblastic leukemia: state of the art and new trends

Abstract

Recently, much progress has been made in understanding the biology, genetics and therapy of acute lymphoblastic leukemia a€“ a heterogeneous group of lymphoid disorders resulting from a monoclonal proliferation and expansion of immature B or T lymphocyte progenitor in the bone marrow, blood, and other organs. The disease is most common in children, but can occur in any age group. ALL in infants aged younger than 12 months is both rare and biologically different from ALL in older children. Children with ALL develop symptoms related to infiltration of blasts in the bone marrow, lymphoid system, and extramedullary sites, such as the central nervous system. In most patients, the cause of ALL is unknown. Diagnosis of ALL relies on an assessment of morphology, flow cytometry immunophenotyping, and identification of cytogenetic-molecular abnormalities. In ALL immunological markers give information of relevance to prognosis a€“ the worst prognosis is seen in the small minority of cases showing a mature B phenotype. The subtypes of ALL may be further determined by genomic profiling. Recent genomewide analyses of DNA copynumber abnormalities have identified numerous recurring genetic alterations in ALL. Mutations of genes encoding transcriptional regulators of B lymphoid development, including PAX5, EBF1, and IKZF1, occur in more than 40% of patients with B-cella€“progenitor ALL. Children whose ALL cells exhibit in vitro resistance to antileukemic agents have a substantially worse prognosis than children whose ALL cells are drug-sensitive. The currently accepted philosophy behind treatment of pediatric ALL is based on the recognition of the heterogeneity of the disease and the definition of specific cytogenetic-molecular abnormalities.

Keywords

• acute lymphoblastic leukemia, children, diagnosis, therapy