Surrogate marker profiles for genetic lesions in acute leukemias

The basic hypothesis of surrogate marker profiles is that individual genetic lesions result in characteristic distortions of the cellular phenotype with some predictable consistency that can be exploited by sophisticated immunophenotyping. While cytogenetic and molecular aberrancies currently are accepted prognostic predictors in acute leukemias, single antigen expression and even antigenic profiles rarely impact on prognosis. However, increasingly, phenotypes are delineated which can serve as surrogates for underlying genetic aberrations of clinical importance. This development is of particular significance as antileukemic therapy becomes available that targets any component of the disturbed molecular pathways associated with these genetic lesions. This chapter will focus on established surrogate marker profiles, such as those for PML/RARα, AML1/ETO, FLT3-gene mutated acute lymphocytic leukemia (ALL), and BCR/ABL(POS) ALL. As the list of therapeutic targets grows, the role of surrogate antigen profiles will grow, as they can predict for the efficacy of targeted approaches in lieu of expensive, time-consuming and not always accessible genetic analyses.