Future Directions

Research developments in terms of our understanding of the biology of AML and the clinical evaluation of novel targeted therapeutic approaches are clearly going to have an impact on the range of assays that will need to be developed and offered by molecular pathology laboratories in the future. There is considerable interest in determining whether gene expression profiling using microarrays34-36 will yield further insights into the etiology of AML and lead to further refinement of the classification of the disease, enabling development of more rational treatment approaches. Large-scale gene expression profiling efforts may yield information that reliably distinguishes subgroups of patients with distinct prognoses and potentially identifies those who are likely to be highly sensitive or resistant to particular therapeutic agents. If these expectations are realized it could have major implications for hematology laboratories, leading to investigation of expression profiles of a more limited number of genes using Gene Chips and/or RQ-PCR as a key component of the diagnostic workup. Further information regarding individual variation in disease response according to polymorphisms in genes encoding components of drug-metabolizing pathways could see more widespread introduction of single nucleotide polymorphism (SNP) assays. Such approaches, in conjunction with flow cytometry, could be used to define resistance phenotypes, leading to the use of resistance modulators in suitable patients. Development of appropriate laboratory assays also is essential to determine whether novel therapeutic approaches designed, for example, to modulate drug resistance pathways or mediate gene reactivation through targeting histone deacetylases (HDACs) or DNA methyltransferases are indeed having their desired effect on the relevant pathways in vivo.

In addition to the expansion of the repertoire of assays used to evaluate newly diagnosed patients with AML, the next few years are likely to see more widespread use of MRD assessment to determine treatment approaches for patients with the disease. For patients with fusion gene transcripts, RQ-PCR is clearly the best approach, and international efforts are under way to establish optimal time points for MRD sampling and thresholds of fusion gene expression that are predictive of long-term outcome. A key challenge is to determine the most appropriate way to monitor patients who lack a suitable fusion gene marker, whether by RQ-PCR detection of genes that are typically overexpressed in AML or by use of flow cytometry. It is clear that the pathology laboratory is set to play an ever-increasingly important role in optimizing and individualizing the management of patients with AML.

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