AML Mutational Analysis Profile
Test Code
P AML
Test Synonyms
FLT3 & NPM1 mutations
Associations
Acute Myelogenous Leukemia (AML)
Methodology
Polymerase Chain Reaction (PCR), Gene amplification of FLT3 (exons 14 and 15) and NPM1 (exon 12) with fluorescently-labeled primers followed by detection with capillary electrophoresis
Testing for FLT3 will be performed at Laboratory for Personalized Molecular Medicine (LabPMM.com) of San Diego, California pursuant to patents licensed from Takara Bio of Otsu, Japan.
Testing for FLT3 will be performed at Laboratory for Personalized Molecular Medicine (LabPMM.com) of San Diego, California pursuant to patents licensed from Takara Bio of Otsu, Japan.
CPT Codes
83891 - Isolation nuclic acid
83898 x3 - Amplification nucleic acid, single primer pair
83892 - Enzymatic digestion
83909 x3 - Separation and identification by capillary electrophoresis
83912 - Interpretation and report
83898 x3 - Amplification nucleic acid, single primer pair
83892 - Enzymatic digestion
83909 x3 - Separation and identification by capillary electrophoresis
83912 - Interpretation and report
Turnaround Time
Less than 4 days
Specimen Requirements
5.0 mL EDTA (min. 3.0 mL) whole blood or (min. 2.0 mL) bone marow
Specimen Stability
18-25°C for 1 week; 4°C for up to 14 days
Storage & Handling
Ship at ambient temperature, cool in summer. (Do not allow ice pack to directly contact sample.)
Causes for Rejection
Improper specimen labeling; Insufficient sample volume; Clotted specimen; Specimen older than 7 days
Reference Range
FLT3: Negative, Positive
NPM1: Negative, Positive
Related Content
A negative FLT3 and Negative NPM1 result can be reflexed to CEBPA mutation analysis when requested.
Description
This test provides additional prognostic information for CN-AML patients. FLT3-ITD-positive patients may be candidates for future therapies with FLT3 tyrosine kinase inhibitors.
Cytogenetic abnormalities in acute myeloid leukemia (AML) are useful diagnostic markers and prognostic factors for remission, relapse and survival. However, 40-49% of adults and 25% of children with AML are cytogenetically normal (CN) and are classified with a prognosis with intermediate risk. Several molecular markers of prognostic significance have been identified in CN-AML patients.
Internal tandem duplications (ITD) in exons 14 and 15 of the FMS-related tyrosine kinase 3 (FLT3) gene are detected in 28-33% of CN-AML patients. FLT3-ITD mutations are associated with a poorer prognosis. Nucleophosmin member 1 (NPM1) mutations in exon 12 are found in 46-60% of CN-AML patients. NPM1 mutations in patients that lack FLT3-ITD are associated with a significantly improved outcome, but NPM1 mutations do not impact the poor outcome of patients with FLT3-ITD.
Cytogenetic abnormalities in acute myeloid leukemia (AML) are useful diagnostic markers and prognostic factors for remission, relapse and survival. However, 40-49% of adults and 25% of children with AML are cytogenetically normal (CN) and are classified with a prognosis with intermediate risk. Several molecular markers of prognostic significance have been identified in CN-AML patients.
Internal tandem duplications (ITD) in exons 14 and 15 of the FMS-related tyrosine kinase 3 (FLT3) gene are detected in 28-33% of CN-AML patients. FLT3-ITD mutations are associated with a poorer prognosis. Nucleophosmin member 1 (NPM1) mutations in exon 12 are found in 46-60% of CN-AML patients. NPM1 mutations in patients that lack FLT3-ITD are associated with a significantly improved outcome, but NPM1 mutations do not impact the poor outcome of patients with FLT3-ITD.
References
- Mrozek K. et al. (2007). Clinical relevance of mutations and gene-expression changes in adult acute myeloid leukemia with normal cytogenetics: are we ready for a prognostically prioritized molecular classification? Blood. 109:431-448.
- Baldus C. et al. (2007). Clinical outcome of de novo acute myeloid leukemia patient with normal cytogenetics is affected by molecular genetic alterations: a concise review. Br. J. Hematol. 137:387-400.
- Swerdlow SH, Camo E, Harris NL, Jaffe ES, et al (2008). WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th Edition.
- Frankfurt O, Licht J, Tallman M (2007). Molecular characterization of acute myeloid leukemia and its impact on treatment. Curr Opin Oncol. 19:635-649.
- Gale RE, Green C, Allen C, et al (2008). The impact of FLT3 internal tandem duplication mutant level, number, size, and interaction with NPM1 mutations in a large cohort of young adult patients with acute myeloid leukemia. Blood. 111: 2776-2784.
- NCCN guidelines Acute myeloid leukemia
