Acute Myeloid Leukemia Molecular Genetic Testing

Content Review: October 2019 Last Update:
Detect and quantitate gene alterations/translocations/
inversions. Use for minimal residual disease (MRD) and relapse risk monitoring.
Use for diagnosis, prognosis, and management. Not intended for MRD monitoring.

Acute myeloid leukemias (AMLs) are a heterogeneous group of disorders characterized by the clonal expansion of myeloid precursors in the peripheral blood, bone marrow, and/or other tissues, which results in impaired hematopoiesis and bone marrow failure.     AML is the most common acute leukemia in adults (~80% of leukemia cases) and accounts for the largest number of annual deaths from leukemia in the United States.   Gene alterations, along with translocations and inversions, carry prognostic importance in AML. In addition to large chromosomal rearrangements, molecular changes have also been implicated in the development of AML. A comprehensive evaluation of several molecular markers, including FLT3, NPM1, IDH1, and IDH2, is important for risk assessment and prognostication in certain patients with AML, and may guide treatment decisions. 

For more information on next generation sequencing testing for AML, refer to the Acute Myeloid Leukemia Mutation Panel by Next Generation Sequencing Test Fact Sheet.

Testing Strategy

At diagnosis, the minimum AML workup includes a bone marrow aspirate for morphology, flow cytometric immunophenotyping, cytogenetics (eg, karyotyping and fluorescence in situ hybridization [FISH]), and appropriate molecular genetic testing.   

Disease Overview

Incidence

>20,0000 cases/year in the U.S. 

Age of Onset

Median is 67 years 

Symptoms

  • Symptoms resulting from thrombocytopenia, neutropenia, and anemia due to the accumulation of blasts in the marrow 
  • Morphologic hallmark: excessive accumulation of blasts (typically >20%) and other defined immature cells which affect one or more myeloid lineage 

Test Interpretation

For more detailed information on the prognostic significance of molecular markers in AML, see the ARUP Consult Acute Myeloid Leukemia topic.

Sensitivity/Specificity

GeneMethodologyAnalytical SensitivityAnalytical Specificity (%)
FLT3 ITD and TKDPCR/CESignal ratio of 0.05 for ITD and 0.05 for TKD D835100
IDH1 and IDH2PCR/sequencing40% mutated cells100
NPM1Quantitative reverse transcription PCR1:100,000100
CBFB-MYH11aQuantitative reverse transcription PCR1:10,000100
PML-RARAaQuantitative reverse transcription PCR1:10,00085
RUNX1-RUNX1T1aQuantitative reverse transcription PCR1:100,000100

aThese fusions can initially be screened by FISH but are also useful in monitoring for MRD.

CE, capillary electrophoresis; PCR, polymerase chain reaction

Limitations

  • Variants outside the targeted regions or below the limit of detection will not be identified.
  • Results must always be interpreted within the patient's clinical context and in conjunction with other relevant data and should not be used alone for a diagnosis of malignancy.

References