Acute Myeloid Leukemia (AML) via the CEBPA Gene

  • Summary and Pricing
  • Clinical Features and Genetics
  • Citations
  • Methods
  • Ordering/Specimens
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Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
996 CEBPA$580.00 81403 Add to Order
Targeted Testing

For ordering targeted known variants, please proceed to our Targeted Variants landing page.

Turnaround Time

The great majority of tests are completed within 18 days.

Clinical Sensitivity

CEBPA mutations are found in approximately 9% of AML cases and in 15-18% of normal karyotype AML (Klein and Marcucci. Gene Reviews 2010; Leroy et al. Leukemia 19(3):329-334, 2005; Frohling et al. J Clin Oncol 22(4):624-633, 2004).

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Deletion/Duplication Testing via aCGH

Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
600 CEBPA$690.00 81479 Add to Order
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Turnaround Time

The great majority of tests are completed within 28 days.

Clinical Sensitivity

To date, no gross deletions or duplications have been reported in CEBPA (Human Gene Mutation Database).

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Clinical Features

Acute Myeloid Leukemia (AML) comprises a phenotypically and genetically heterogeneous group of neoplastic disorders characterized by the accumulation of myeloid precursor cells in the bone marrow and blood. The malignant precursor cells display increased proliferation and a block in normal differentiation and maturation. Accumulating malignant cells replace normal bone marrow and interfere with normal blood cell production causing a decrease in red blood cells and platelets. Symptoms include easy bruising and bleeding, fatigue, and increased risk of infection due to a lack of normal white blood cells. Pathogenic variants have been identified in several genes in AML patients.  Approximately 13,000 cases of AML per year are diagnosed in the United States, and according to the results of several studies, CEBPA variants have been identified in 15-18% of cytogenetically normal AML cases (Leroy et al. Leukemia 19(3):329-334, 2005; Frohling et al. J Clin Oncol 22(4):624-633, 2004). CEBPA variants are found in cases of both familial AML and sporadic AML, though instances of the former are rare. The age of onset of AML resulting from CEBPA mutations varies, but is generally earlier in cases of familial AML (early childhood to adult onset) than in cases of sporadic AML (onset around fifth or sixth decade) (Klein and Marcucci. GeneReviews, 2010). Studies so far have indicated that the prognosis of patients with CEBPA-related AML is favorable (Preudhomme et al. Blood 100(8):2717-2723, 2002; Frohling et al., 2004; Bienz et al. Clin Cancer Res 11(4):1416-1624, 2005) thereby highlighting the importance of cytogenetic and molecular testing for AML patients.


CEBPA gene mutations are identified in 15-18% of cytogenetically normal AML cases (Leroy et al., 2005; Frohling et al., 2004). Only a few cases of familial AML have been reported (Smith et al. N Engl J Med 351(23):2403-2407, 2004; Renneville et al. Leukemia 23(4):804-806, 2009), and pathogenic variants in CEBPA displayed a dominant mode of inheritance with high penetrance. CEBPA encodes the transcription factor and tumor suppressor CCAATT enhancer binding protein alpha (C/EBPα) which is upregulated during granulocyte differentiation (Scott et al. Blood 80(7):1725-1735, 1992; Radomska et al. Mol Cell Biol 18(7):4301-4314, 1998). The CEBPA protein consists of two N-terminal transactivation domains and C-terminal leucine zipper and basic domains mediating homo- and hetero-dimerization and DNA-binding. Mutations in CEBPA typically involve either N-terminal frameshifts that result in truncated protein or C-terminal in-frame insertions or deletions that affect the DNA binding domain (Pabst et al. Nat Genet 27(3):263-270, 2001). No obvious genotype-phenotype correlations have been identified.

Testing Strategy

This test involves bidirectional Sanger DNA sequencing of the one coding exon of the CEBPA gene plus ~10 bp of flanking non-coding DNA on either side of the exon. We will also perform targeted sequence analysis (Test #100) in family members of patients with a known mutation or to confirm research results.

NOTE: Mutations identified in blood specimens during active AML cannot be categorized as acquired or familial without additional information such as a family history and pedigree, and/or results from testing a non-involved specimen such as skin fibroblasts. Also, in cases of sporadic AML resulting from CEBPA variants, low levels of leukemic cells in bone marrow or blood specimens for example, may not produce a signal that exceeds our limits of detection; negative results from testing should be interpreted in the context of this caveat (see Analytical Limitations for more details).

Indications for Test

Family history of AML, an abundance of French-American-British (FAB) Cooperative Group AML Classification subtypes M1 or M2 as established by review of cellular morphology and cytochemistries in blasts in peripheral blood or bone marrow aspirate, Auer rods in blasts in peripheral blood smear or bone marrow aspirate (Auer rods are abnormal, needle-shaped or round, light blue or pink-staining inclusions found in the cytoplasm of leukemic cells), aberrant CD7 expression on blasts in peripheral blood or bone marrow as demonstrated by flow cytometry (Klein and Marcucci. GeneReviews, 2010).  


Official Gene Symbol OMIM ID
CEBPA 116897
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Aml - Acute Myeloid Leukemia 601626


Genetic Counselors
  • Bienz, M. et al. (2005). "Risk assessment in patients with acute myeloid leukemia and a normal karyotype." Clin Cancer Res 11(4):1416-1424. PubMed ID: 15746041
  • Frohling S. et al. (2004). "CEBPA mutations in younger adults with acute myeloid leukemia and normal cytogenetics: prognostic relevance and analysis of cooperating mutations." J Clin Oncol 22(4):624-633. PubMed ID: 14726504
  • Human Gene Mutation Database (Bio-base).
  • Klein R.D. and Marcucci G. (2010) "Familial Acute Myeloid Leukemia (AML) with Mutated CEBPA." GeneReviews. PubMed ID: 20963938
  • Leroy, H. et al. (2005). "CEBPA point mutations in hematological malignancies." Leukemia 19(3):329-334. PubMed ID: 15674366
  • Pabst T. et al. (2001). "Dominant-negative mutations of CEBPA, encoding CCAAT/enhancer binding protein-alpha (C/EBPalpha), in acute myeloid leukemia." Nat Genet 27(3):263-270.  PubMed ID: 11242107
  • Preudhomme, C. et al. (2002). "Favorable prognostic significance of CEBPA mutations in patients with de novo acute myeloid leukemia: a study from the Acute Leukemia French Association (ALFA)." Blood 100(8):2717-2723.  PubMed ID: 12351377
  • Radomska H.S. et al. (1998). "CCAAT/enhancer binding protein alpha is a regulatory switch sufficient for induction of granulocytic development from bipotential myeloid progenitors." Mol Cell Biol (7):4301-4314. PubMed ID: 9632814
  • Renneville, A. et al. (2009). "Another pedigree with familial acute myeloid leukemia and germline CEBPA mutation." Leukemia 23(4):804-806. PubMed ID: 18946494
  • Scott L.M. et al. (1992). "A novel temporal expression pattern of three C/EBP family members in differentiating myelomonocytic cells." Blood 80(7):1725-1735. PubMed ID: 1391942
  • Smith, M.L. et al. (2004). "Mutation of CEBPA in familial acute myeloid leukemia." N Engl J Med 351(23):2403-2407. PubMed ID: 15575056
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Bi-Directional Sanger Sequencing

Test Procedure

Nomenclature for sequence variants was from the Human Genome Variation Society (  As required, DNA is extracted from the patient specimen.  PCR is used to amplify the indicated exons plus additional flanking non-coding sequence.  After cleaning of the PCR products, cycle sequencing is carried out using the ABI Big Dye Terminator v.3.0 kit.  Products are resolved by electrophoresis on an ABI 3730xl capillary sequencer.  In most cases, sequencing is performed in both forward and reverse directions; in some cases, sequencing is performed twice in either the forward or reverse directions.  In nearly all cases, the full coding region of each exon as well as 10 bases of non-coding DNA flanking the exon are sequenced.

Analytical Validity

As of February 2018, we compared 26.8 Mb of Sanger DNA sequence generated at PreventionGenetics to NextGen sequence generated in other labs. We detected only 4 errors in our Sanger sequences, and these were all due to allele dropout during PCR. For Proficiency Testing, both external and internal, in the 14 years of our lab operation we have Sanger sequenced roughly 14,300 PCR amplicons. Only one error has been identified, and this was an error in analysis of sequence data.

Our Sanger sequencing is capable of detecting virtually all nucleotide substitutions within the PCR amplicons. Similarly, we detect essentially all heterozygous or homozygous deletions within the amplicons. Homozygous deletions which overlap one or more PCR primer annealing sites are detectable as PCR failure. Heterozygous deletions which overlap one or more PCR primer annealing sites are usually not detected (see Analytical Limitations). All heterozygous insertions within the amplicons up to about 100 nucleotides in length appear to be detectable. Larger heterozygous insertions may not be detected. All homozygous insertions within the amplicons up to about 300 nucleotides in length appear to be detectable. Larger homozygous insertions may masquerade as homozygous deletions (PCR failure).

Analytical Limitations

In exons where our sequencing did not reveal any variation between the two alleles, we cannot be certain that we were able to PCR amplify both of the patient’s alleles. Occasionally, a patient may carry an allele which does not amplify, due for example to a deletion or a large insertion. In these cases, the report contains no information about the second allele.

Similarly, our sequencing tests have almost no power to detect duplications, triplications, etc. of the gene sequences.

In most cases, only the indicated exons and roughly 10 bp of flanking non-coding sequence on each side are analyzed. Test reports contain little or no information about other portions of the gene, including many regulatory regions.

In nearly all cases, we are unable to determine the phase of sequence variants. In particular, when we find two likely causative mutations for recessive disorders, we cannot be certain that the mutations are on different alleles.

Our ability to detect minor sequence variants, due for example to somatic mosaicism is limited. Sequence variants that are present in less than 50% of the patient’s nucleated cells may not be detected.

Runs of mononucleotide repeats (eg (A)n or (T)n) with n >8 in the reference sequence are generally not analyzed because of strand slippage during PCR and cycle sequencing.

Unless otherwise indicated, the sequence data that we report are based on DNA isolated from a specific tissue (usually leukocytes). Test reports contain no information about gene sequences in other tissues.

Deletion/Duplication Testing via Array Comparative Genomic Hybridization

Test Procedure

Equal amounts of genomic DNA from the patient and a gender matched reference sample are amplified and labeled with Cy3 and Cy5 dyes, respectively. To prevent any sample cross contamination, a unique sample tracking control is added into each patient sample. Each labeled patient product is then purified, quantified, and combined with the same amount of reference product. The combined sample is loaded onto the designed array and hybridized for at least 22-42 hours at 65°C. Arrays are then washed and scanned immediately with 2.5 µM resolution. Only data for the gene(s) of interest for each patient are extracted and analyzed.

Analytical Validity

PreventionGenetics' high density gene-centric custom designed aCGH enables the detection of relatively small deletions and duplications within a single exon of a given gene or deletions and duplications encompassing the entire gene. PreventionGenetics has established and verified this test's accuracy and precision.

Analytical Limitations

Our dense probe coverage may allow detection of deletions/duplications down to 100 bp; however due to limitations and probe spacing this cannot be guaranteed across all exons of all genes. Therefore, some copy number changes smaller than 100-300 bp within a targeted large exon may not be detected by our array.

This array may not detect deletions and duplications present at low levels of mosaicism or those present in genes that have pseudogene copies or repeats elsewhere in the genome.

aCGH will not detect balanced translocations, inversions, or point mutations that may be responsible for the clinical phenotype.

Breakpoints, if occurring outside the targeted gene, may be hard to define.

The sensitivity of this assay may be reduced when DNA is extracted by an outside laboratory.

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Ordering Options

myPrevent - Online Ordering
  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.


(Delivery accepted Monday - Saturday)

  • Collect 3 ml -5 ml (5 ml preferred) of whole blood in EDTA (purple top tube) or ACD (yellow top tube). For Test #500-DNA Banking only, collect 10 ml -20 ml of whole blood.
  • For small babies, we require a minimum of 1 ml of blood.
  • Only one blood tube is required for multiple tests.
  • Ship blood tubes at room temperature in an insulated container. Do not freeze blood.
  • During hot weather, include a frozen ice pack in the shipping container. Place a paper towel or other thin material between the ice pack and the blood tube.
  • In cold weather, include an unfrozen ice pack in the shipping container as insulation.
  • At room temperature, blood specimen is stable for up to 48 hours.
  • If refrigerated, blood specimen is stable for up to one week.
  • Label the tube with the patient name, date of birth and/or ID number.


(Delivery accepted Monday - Saturday)

  • Send in screw cap tube at least 5 µg -10 µg of purified DNA at a concentration of at least 20 µg/ml for NGS and Sanger tests and at least 5 µg of purified DNA at a concentration of at least 100 µg/ml for gene-centric aCGH, MLPA, and CMA tests, minimum 2 µg for limited specimens.
  • For requests requiring more than one test, send an additional 5 µg DNA per test ordered when possible.
  • DNA may be shipped at room temperature.
  • Label the tube with the composition of the solute, DNA concentration as well as the patient’s name, date of birth, and/or ID number.
  • We only accept genomic DNA for testing. We do NOT accept products of whole genome amplification reactions or other amplification reactions.


(Delivery preferred Monday - Thursday)

  • PreventionGenetics should be notified in advance of arrival of a cell culture.
  • Culture and send at least two T25 flasks of confluent cells.
  • Some panels may require additional flasks (dependent on size of genes, amount of Sanger sequencing required, etc.). Multiple test requests may also require additional flasks. Please contact us for details.
  • Send specimens in insulated, shatterproof container overnight.
  • Cell cultures may be shipped at room temperature or refrigerated.
  • Label the flasks with the patient name, date of birth, and/or ID number.
  • We strongly recommend maintaining a local back-up culture. We do not culture cells.
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