CEBPA Mutation Analysis

What the laboratory says this test is for

This testing, consisting of FLT3, NPM-1, and CEBPA, is recommended in the NCCN guidelines for determination of AML risk status in patients with cytogenetically normal AML. The presence of CEBPA gene mutations is associated with increased disease-free survival and overall survival. Mutations in NPM1 gene is a predictor of favorable prognosis and good response to induction chemotherapy. The presence of (FLT3) internal tandem duplication is associated with short disease-free survival.

What the laboratory says this test is for

FLT3 testing is established as a prognostic marker associated with poor prognosis (high percentage of bone marrow blast cells, increased risk of relapse from CR, and reduced survival). However, with the advent of FLT3 inhibitors it is now also a test for targeted therapy in AML. The multi-kinase inhibitor Midostaurin, in combination with chemotherapy, is a targeted agent that significantly prolongs survival in patients with newly diagnosed FLT3-mutated AML and was recently approved by the Food and Drug Administration (FDA). Recently, the European LeukemiaNet recommends FLT3 testing (both tyrosine kinase domain; TKD and internal tandem duplication; ITD mutations) for all patients with AML, with results required within 3 days.In de novo AML, IDH1/2 mutations are associated with older age, normal karyotype, and NPM1 mutations. IDH1/2 and TET2 mutations are mutually exclusive. IDH1 mutations are found in 6-16% of de novo AML and are associated with a poorer outcome in patients treated with intensive chemotherapy, even in patients with favorable prognosis as per European LeukemiaNet (ELN) classification. IDH2 mutations are found in 8-19% of de novo AML. The prognostic impact of IDH2 mutations differs strongly and is less predictive overall. In the past 2 years, two mutant IDH (mutIDH) inhibitors, Enasidenib (AG-221), and Ivosidenib (AG-120), have been FDA-approved for IDH-mutant relapsed or refractory acute myeloid leukemia (AML) based on phase 1 safety and efficacy data and continue to be studied in trials in hematologic malignancies.NPM1 mutations have an overall favorable effect on the outcome for AML. Patients with FLT3-ITD and NPM1 mutations have improved outcomes when compared to patients with those who only have the FLT3-ITD mutation, but those with both mutations had a poorer prognosis than patients with only NPM1 mutations.CEBPA mutated AML into separates into 2 prognostic subsets: (1) CEBPA double-mutated AML and (2) CEBPA single-mutated AML. Favorable outcome was restricted to double-mutated AML cases and is an independent prognostic factor for a favorable outcome. FLT3-ITD, NPM1, ASXL1 and RUNX1 mutations are detected more frequently in CEBPA single-mutated AML.TP53 mutations correlate with poor response to chemotherapy and poor survival in patients with or without complex karyotype. There is a decreased frequency of FLT3, and NPM1 mutations in TP53 mutated AML.

What the laboratory says this test is for

The CEBPA gene, a myeloid transcription factor, is mutated in a subset of acute myeloid leukemia (AML), particularly those with chromosome analyses showing normal diploid karyotype, Cytogenetically Normal (CN). CN-AML that have CEBPA mutations show favorable outcome compared to other groups of CN-AML. Testing for CEBPA mutation, along with NPM1 (test code 16158-NPM (Exon 12) Mutation Analysis, Cell-based) is recommended for all patients with CN-AML.