Prognostic and Predictive Biomarkers in Precursor B-cell Acute Lymphoblastic Leukemia

Abstract

Precursor B-cell acute lymphoblastic leukemia (B-ALL) is a hematologic malignancy characterized by clonal proliferation of abnormal B-cell precursors in the bone marrow. Most of the B-ALL cases are diagnosed in children, although it can present at any age. Thanks to the tremendous advances in our understanding of its biology, identification of more and more prognostic and predictive biomarkers, and application of individualized risk-adjusted treatment, B-ALL has become the most curable malignancy in children, with a long-term survival rate close to 90% in newly diagnosed patients. However, the prognosis of B-ALL remains dismal in adults and children with relapse. Relapsed B-ALL continues to be the leading cause of cancer-related death in children and young adults. Risk stratification is currently based on age, white blood cell count, early therapeutic response, and chromosomal abnormalities such as ploidy and translocations. Recent advances in molecular diagnostic technologies have led to a rapid expansion of the list of molecular biomarkers associated with B-ALL, which show promise to improve the accuracy of risk prediction, and eventually achieve better risk-adapted treatment and clinical outcome. In this chapter, we provide an overview of the prognostic and predictive biomarkers in B-ALL, including some recently identified genomic alterations with significant prognostic impact.