Evaluation of acute myeloid leukemia 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
This test includes next-generation sequencing to evaluate for the following 4 genes: FLT3, IDH1, IDH2, and TP53.
Next-generation sequencing detection of somatic gene mutations, including type, pattern, and distribution, has diagnostic, prognostic, and potential therapeutic implications for patients with hematologic cancers, such as acute myeloid leukemia (AML).
This test identifies targets for more accurate therapeutic management of AML.
For more information see Acute Myeloid Leukemia: Relapsed with Previous Remission Testing Algorithm
For a list of the genes and exons targeted by this test see Targeted Genes Interrogated by Next-Generation Sequencing, Acute Myeloid Leukemia, Therapeutic, 4-Gene Panel
Next-Generation Sequencing (NGS)
FLT3
IDH1
IDH2
Next gen sequencing of leukemia (AML)
Next Gen Sequencing Test
NGS cancer panel, hematologic
NGS hematologic malignancies
Somatic mutation detection by next generation sequencing (NGS), hematologic
TP53
Enasidenib therapy
Midostaurin therapy
For more information see Acute Myeloid Leukemia: Relapsed with Previous Remission Testing Algorithm
For a list of the genes and exons targeted by this test see Targeted Genes Interrogated by Next-Generation Sequencing, Acute Myeloid Leukemia, Therapeutic, 4-Gene Panel
Varies
This test focuses specifically on the gene mutations that are most utilized for therapeutic management of acute myeloid leukemias (AML) and is a subset of NGSHM / OncoHeme Next-Generation Sequencing for Myeloid Neoplasms, Varies. If a wider gene mutation analysis is desired or the indication is for a myeloid malignancy other than AML, order NGSHM.
Peripheral blood and bone marrow specimens must arrive within 14 days of collection.
The following information is required:
1. Clinical diagnosis
2. Pertinent clinical history, including disease phase (diagnostic, remission, relapse/refractory) and therapy status (especially if patient has received a hematopoietic stem cell transplant).
3. Clinical or morphologic suspicion
4. Date of collection
5. Specimen source
Question ID | Description | Answers |
---|---|---|
MP040 | Specimen Type | |
NGAID | Diagnosis/Indication |
Submit only 1 of the following specimens:
Specimen Type: Bone marrow aspirate (preferred)
Container/Tube:
Preferred: Lavender top (EDTA) or yellow top (ACD)
Acceptable: Green top (heparin)
Specimen Volume: 2 mL
Collection Instructions:
1. Invert several times to mix bone marrow.
2. Send bone marrow specimen in original tube. Do not aliquot
3. Label specimen as bone marrow.
Specimen Stability: Ambient (preferred)/Refrigerate
Specimen Type: Peripheral blood
Container/Tube:
Preferred: Lavender top (EDTA) or yellow top (ACD)
Acceptable: Green top (heparin)
Specimen Volume: 3 mL
Collection Instructions:
1. Invert several times to mix blood.
2. Send whole blood specimen in original tube. Do not aliquot
3. Label specimen as blood.
Specimen Stability: Ambient (preferred)/Refrigerate
Specimen Type: Extracted DNA from blood or bone marrow
Container/Tube: 1.5- to 2-mL tube with indication of volume and concentration of the DNA
Specimen Volume: Entire specimen
Collection Instructions: Label specimen as extracted DNA and source of specimen
Specimen Stability: Frozen (preferred)/Refrigerate/Ambient
1. Hematopathology Patient Information (T676)
2. If not ordering electronically, complete, print, and send a Hematopathology/Cytogenetics Test Request (T726) with the specimen.
Blood, Bone Marrow: 1 mL
Extracted DNA: 100 mcL at 20 ng/mcL concentration
Gross hemolysis | Reject |
Gross lipemia | OK |
Bone marrow biopsies Slides Paraffin shavings or frozen tissues Paraffin-embedded tissues Paraffin-embedded bone marrow aspirates Moderately to severely clotted | Reject |
Specimen Type | Temperature | Time | Special Container |
---|---|---|---|
Varies | Varies (preferred) | 14 days |
Evaluation of acute myeloid leukemia 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
This test includes next-generation sequencing to evaluate for the following 4 genes: FLT3, IDH1, IDH2, and TP53.
For more information see Acute Myeloid Leukemia: Relapsed with Previous Remission Testing Algorithm
For a list of the genes and exons targeted by this test see Targeted Genes Interrogated by Next-Generation Sequencing, Acute Myeloid Leukemia, Therapeutic, 4-Gene Panel
Next-generation sequencing 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.
An interpretive report will be provided.
Mutations (gene alterations) identified, if present, using human reference genome build GRCh37 (hg19). An interpretive report will be provided.
This test is a targeted next-generation sequencing assay that encompasses 4 genes with variable full exon, partial region (including select intronic or noncoding 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 variant 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), and these may not be clearly distinguishable from tumor-associated mutations. Some apparent mutations classified as variants of undetermined significance may represent rare or low-frequency polymorphisms.
Prior treatment for hematologic malignancy could affect the results obtained in this assay. In particular, a prior allogeneic hematopoietic stem cell transplant 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.
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 Nov 28;122(23):3741-3748. doi: 10.1182/blood-2013-06-460295
3. Amatangelo MD, Quek L, Shih A, et al: Enasidenib induces acute myeloid leukemia cell differentiation to promote clinical response. Blood. 2017 Aug 10;130(6):732-741. doi: 10.1182/blood-2017-04-779447
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 Aug 3;377(5):454-464. doi: 10.1056/NEJMoa1614359
5 Stein EM, DiNardo CD, Pollyea DA, et al: Enasidenib in mutant IDH2 relapsed or refractory acute myeloid leukemia. Blood. 2017 Aug;130(6):722-731. doi: 10.1182/blood-2017-04-779405
Next-generation sequencing is performed for the presence of a mutation in targeted regions of the following 4 genes: FLT3, IDH1, IDH2, and TP53. See Targeted Genes Interrogated by Next-Generation Sequencing, Acute Myeloid Leukemia, Therapeutic, 4-Gene Panel for details regarding the targeted gene regions identified in this test. This is a laboratory-developed test using research use only reagents. Extracted DNA from the clinical specimen is fragmented, adapter ligated, and a sequence library of fragments is prepared using a custom capture hybridization method. Individual patient samples are indexed ("bar-coded") for identification and the library is sequenced on an Illumina platform. Sequence data are processed through a bioinformatics pipeline and a variant call file is generated for final analysis and reporting.(Unpublished Mayo method)
Monday, Wednesday
This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.
81120
81121
81245
81246
81352
Test Id | Test Order Name | Order LOINC Value |
---|---|---|
NGAMT | AML 4 Gene Panel, Therapeutic | In Process |
Result Id | Test Result Name |
Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
|
---|---|---|
MP040 | Specimen Type | 31208-2 |
NGAID | Diagnosis/Indication | 29308-4 |
601698 | NGAMT Result | No LOINC Needed |
601700 | Pathogenic Mutations Detected | 82939-0 |
601699 | Interpretation | 69047-9 |
601701 | Clinical Trials | 82786-5 |
601702 | Variants of Unknown Signficance | 93367-1 |
601703 | Additional Notes | 48767-8 |
601704 | Method Summary | 85069-3 |
601705 | Disclaimer | 62364-5 |
601706 | AML 4 Gene Panel Gene List | 36908-2 |
601707 | Reviewed By: | 18771-6 |