New prognostic markers in acute myeloid leukemia: perspective from the clinic.

Acute myeloid leukemia (AML) is a disease with marked heterogeneity in both response to therapy and survival. Cytogenetics, age, and performance status have long determined prognosis and therapy. The advent of molecular diagnostics has heralded an explosion in new prognostic factors, including gene mutations in KIT, FLT3 (Fms-like tyrosine kinase 3), NPM1 (nucleophosmin 1), and CEBPA (CCAAT enhancer-binding protein-α). Microarray technology can now identify unique gene expression signatures associated with prognosis. Similarly microRNA expression, single nucleotide polymorphism arrays, and DNA methylation signatures have recently described important new prognostic subgroups of AML, and are contributing to our understanding of AML disease biology. Combined with proteomic profiling, these technologies have helped identify new targets and signaling pathways, and may soon help to identify individual patients likely to benefit from specific therapies, including allogeneic hematopoietic cell transplantation. In summary, new clinical and molecular prognostic markers have begun to significantly improve our understanding of AML biology. We are now close to a time when we will be able to use these prognostic factors and technologies to identify new targets for therapy and to determine who may benefit from that therapy, and ultimately change how we treat individual patients with AML.