Intracellular signaling pathways involved in childhood acute lymphoblastic leukemia; molecular targets

Abstract

Acute lymphoblastic leukemia (ALL) is a malignant disease characterized by an uncontrolled proliferation of immature lymphoid cells. ALL is the most common hematologic malignancy in early childhood, and it reaches peak incidence between the ages of 2 and 3 years. The prognosis of ALL is associated with aberrant gene expression, in addition to the presence of numerical or structural chromosomal alterations, age, race, and immunophenotype. The Relapse rate with regard to pharmacological treatment rises in childhood; thus, the expression of biomarkers associated with the activation of cell signaling pathways is crucial to establish the disease prognosis. Intracellular pathways involved in ALL are diverse, including Janus kinase/Signal transducers and transcription activators (JAK-STAT), Phosphoinositide-3- kinase–protein kinase B (PI3K-AKT), Ras mitogen-activated protein kinase (Ras-MAPK), Glycogen synthase kinase-3b (GSK-3b), Nuclear factor-kappa beta (NF-jB), and Hypoxia-inducible transcription factor 1a (HIF-1a), among others. In this review, we present several therapeutic targets, intracellular pathways, and molecular markers that are being studied extensively at present.