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Molecular Minimal Residual Disease Monitoring in Acute Myeloid Leukemia: Challenges and Future Directions

The Journal of Molecular Diagnostics | Published online: April 21, 2018

Adrian Selim and Andrew S. Moore

The ability to sensitively monitor minimal residual disease (MRD) has played a key role in improving the management and outcomes for a number of leukemias, particularly acute promyelocytic leukemia and childhood acute lymphoblastic leukemia. In contrast, MRD monitoring in acute myeloid leukemia (AML) has been limited by variable test methodologies and a relative paucity of patient-specific MRD markers. Inter and intratumor genetic heterogeneity pose significant challenges for the identification of molecular markers suitable for MRD monitoring in AML, particularly for those cases without structural chromosomal rearrangements associated with fusion genes. Furthermore, the need to discriminate which mutations may be suitable for MRD monitoring creates additional complexity. The mainstay of current molecular MRD monitoring is real-time quantitative PCR, targeting fusion genes, mutations, and gene overexpression. New technologies, particularly next-generation sequencing (NGS) approaches, offer new ways to overcome these limitations. Here, we review the techniques available for molecular MRD monitoring in AML and discuss their utility in clinical practice.

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