Test Catalog

Test ID: NGAMT    
Next-Generation Sequencing Acute Myeloid Leukemia, Therapeutic Gene Mutation Panel (FLT3, IDH1, IDH2, TP53), Varies

Useful For Suggests clinical disorders or settings where the test may be helpful

Evaluation of acute myeloid leukemia (AML) using a focused 4-gene panel at the time of diagnosis, or possibly relapsed or refractory disease, to help determine optimal (eg, targeted) therapeutic approaches

Genetics Test Information Provides information that may help with selection of the correct genetic test or proper submission of the test request

This test includes next-generation sequencing to evaluate for the following 4 genes: FLT3, IDH1, IDH2, and TP53.

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

See Targeted Genes Interrogated by Next-Generation Sequencing, Acute Myeloid Leukemia, Therapeutic, 4-Gene Panel in Special Instructions for a list of the genes and exons targeted by this test.

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Next-generation sequencing (NGS) is a comprehensive molecular diagnostic methodology that can interrogate multiple regions of genomic tumor DNA in a single assay. Many hematologic neoplasms, including acute myeloid leukemia (AML), are characterized by morphologic or phenotypic similarities, but can have characteristic somatic mutations in many genes. In addition, many cases of AML lack a clonal cytogenetic finding at diagnosis (normal karyotype) and can be better classified according to gene mutation profile. The presence and pattern of gene mutations in AML can provide critical prognostic information and may help in guiding therapeutic management decisions by physicians, particularly if targeted therapies are available.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Interpretation Provides information to assist in interpretation of the test results

Mutations (gene alterations) identified, if present, using human reference genome build GRCh37 (hg19). An interpretive report will be provided.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

This test is a targeted next-generation sequencing (NGS) (panel) assay that encompasses 4 genes with variable full exon, partial region (including select intronic or non-coding regions), or hot spot coverage (depending on specific locus). Therefore, this test will not detect other genetic abnormalities in genes or regions outside the specified target areas. The test detects single base substitutions (ie, point mutations), as well as small insertion or deletion type events, but it does not detect gene rearrangements (ie, translocations), gene fusions, copy number alterations, or large scale (segmental chromosome region) deletions and complex changes.

 

This assay does not distinguish between somatic and germline alterations in analyzed gene regions, particularly with variant allele frequencies (VAF) near 50% or 100%. If nucleotide alterations in genes associated with germline mutation syndromes are present and there is also a strong clinical suspicion or family history of malignant disease predisposition, additional genetic testing and appropriate counseling may be indicated. Mutation cells detected between 5% and 10% VAF may indicate low-level (ie, subclonal) tumor populations, although the clinical significance of these findings may not be clear. A low incidence of gene mutations associated with myeloid neoplasms can be detected in nonmalignant hematopoietic cells in individuals with advancing age (clonal hematopoiesis of indeterminate potential, CHIP) and these may not be clearly distinguishable from tumor-associated mutations. Some apparent mutations classified as variants of undetermined significance (VUS) may represent rare or low frequency polymorphisms.

 

Prior treatment for hematologic malignancy could affect the results obtained in this assay. In particular, prior allogeneic hematopoietic stem cell transplant (HSCT) may cause difficulties in resolving somatic or polymorphic alterations, or in assigning variant calls correctly to donor and recipient fractions, if pertinent clinical or laboratory information (eg, chimerism engraftment status) is not provided.

 

Correlation with clinical, histopathologic and additional laboratory findings is required for final interpretation of these results. The final interpretation of results for clinical management of the patient is the responsibility of the managing physician.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Patel JP, Levine RL: How do novel molecular genetic markers influence treatment decisions in acute myeloid leukemia? Hematology Am Soc Hematol Educ Program 2012;2012:28-34

2. Lindsley RC, Ebert BL: The biology and clinical impact of genetic lesions in myeloid malignancies. Blood 2013;23:3741-3748

3. Amatangelo MD, Quek L, Shih A, et al.: Enasidenib induces acute myeloid leukemia cell differentiation to promote clinical response. Blood 2017;130(6):732-741

4 Stone RM, Mandrekar SJ, Sanford BL, et al.: Midostaurin plus Chemotherapy for Acute Myeloid Leukemia with a FLT3 Mutation. N Engl J Med 2017;377:454-464

5 Stein EM, DiNardo CD, Pollyea DA, et al. Enasidenib in mutant IDH2 relapsed or refractory acute myeloid leukemia. Blood 2017;130(6):722-731

Special Instructions Library of PDFs including pertinent information and forms related to the test