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Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
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Related Experiment Video

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Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
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Acute myeloid leukaemia genomics.

Michael Medinger1,2, Jakob R Passweg1

  • 1Division of Haematology, University Hospital Basel, Basel, Switzerland.

British Journal of Haematology
|June 28, 2017
PubMed
Summary

Acute myeloid leukaemia (AML) is a complex cancer. This review highlights new prognostic markers and targetable mutations to guide novel molecularly targeted therapies for AML.

Keywords:
acute myeloid leukaemiagene expressiongene rearrangementmutationstargeted therapies

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Area of Science:

  • Hematology
  • Oncology
  • Molecular Biology

Background:

  • Acute myeloid leukaemia (AML) is a heterogeneous malignancy with complex genetics.
  • Standard AML treatments have seen limited advancement over the past 30 years despite increased understanding of its pathophysiology.

Purpose of the Study:

  • To review advances in prognostic markers for AML.
  • To identify targetable mutations for developing novel molecularly targeted therapies.

Main Methods:

  • Literature review of recent studies on AML genetics and targeted therapies.
  • Analysis of mutation patterns in leukaemogenesis, distinguishing early epigenetic modifier mutations from later signalling molecule mutations.

Main Results:

  • Mutations in epigenetic modifiers (DNMT3A, ASXL1, TET2, IDH1/2) are early events in AML.
  • Mutations in NPM1 or signalling molecules (FLT3, RAS) are typically secondary events.

Conclusions:

  • Understanding the genetic landscape of AML is crucial for therapeutic development.
  • New prognostic markers and targetable mutations are expected to guide future AML treatments.