New strategies in acute myeloid leukemia: redefining prognostic markers to guide therapy

Abstract

Although standard therapy for AML has been relatively constant over the past 2 decades, this may be changing with enhanced technologies allowing for the classification of acute myeloid leukemia (AML) into molecularly distinct subsets. Some specific subsets of AML have an excellent prognosis in response to standard therapy, whereas the poor prognosis of AML associated with specific sets of mutations or chromosomal anomalies requires the development of new therapies. Elucidation of the molecular pathogenesis of AML has led to the development of therapies that affect signaling, apoptosis, protein and intermediate metabolism, the surface of the leukemia cell, leukemia cell/stromal interaction, and epigenetic regulation of gene expression.

Figure 1. Therapeutic Targets in AML

Therapy may be directed against signals generated by growth factor receptors (IL3-R, FLT3) by direct kinase inhibition, by inhibition of downstream signaling (MEK), (PI3K/AKT/mTOR) or by interference with the HSP90 chaperone protein. Additional targets on the horizon include migration/stromal interactions (SDF-1/CXCR4), anti-apoptotic molecules (BCL2), or aberrant DNA methylation and histone methylation. The leukemia cell surface may be targeted by anti-CD33 antibodies, other monoclonal antibodies or tumor vaccines.