CEBPA deficiency, or CEBPA-associated familial acute myeloid leukemia (OMIM #601626, #116897), is a leukemia predisposition syndrome caused by a heterozygous germline mutation in the CEBPA gene. Due to an underlying CEBPA mutation, acute myeloid leukemia (AML) typically occurs earlier than sporadic AML. In addition, it frequently affects multiple members of the same family.

Key Data

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Synonym CEBPA-associated familial AML
Gene product C/EBPα (CCAAT/enhancer binding protein-alpha)
Function Transcription factor with a key role in granulocyte maturation
Heredity Autosomal dominant
Prevalence It is presumed that 5-10% of patients suspected of suffering from CEBPA-associated AML are carriers of a pathogenic CEBPA germline variant.
Genotype-phenotype correlation Germline mutations are typically frameshift mutations in the CEBPA gene region that encodes the N-terminus of the C/EBPα protein, while somatic mutations usually localize to the C-terminal region.
Hereditary C-terminal mutations occur more rarely and are less penetrant.
Penetrance > 80% for AML
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Suspected Diagnosis

A CEBPA deficiency is suspected when the following findings apply:


  • People with AML who have a concomitant AML family history

  • People who develop AML at a young age (< 50 years old)


  • Young patients with AML whose leukemic cells exhibit mutations in both copies of the CEBPA gene

  • A normal karyotype in leukemic cells

  • A predominance of FAB subtypes M1 or M2

  • Auer rods in blasts

  • Aberrant CD7 expression

Genetic Diagnostics

The diagnosis of “CEBPA deficiency” is confirmed by the detection of a germline CEBPA gene mutation through sequence analysis or deletion/duplication analysis. It may be helpful to use panel examinations consisting of multiple genes.

Since CEBPA-associated familial AML develops from cells that have mutations in both copies of the CEBPA gene, leukemic cells frequently exhibit both a germline as well as somatic CEBPA mutations.

Additional Clinical Diagnostics after the Diagnosis Has Been Made

  • HLA typing for a potential stem cell transplant

  • After leukemia is diagnosed, extensive diagnostics according to the respective study protocol

Human Genetics

  • Human genetic linkage of the patient

  • A detailed family history to identify other affected family members and carriers of the mutation

  • Genetic consultation/diagnostics for all family members who are at risk of having CEBPA-associated familial AML

Differential Diagnoses

  • Sporadic AML with a somatic CEBPA mutation

  • AML due to exposure to the environment (benzene, radiation, chemotherapy)

  • Sporadic AML with more than one affected relative

Clinical Presentation

CEBPA-associated familial AML is generally of FAB subtype M1, M2, or – more rarely – M4.

AML associated with familial CEBPA deficiency appears to have an earlier onset than sporadic AML While the average age of diagnosis for the former is 25 years, it greatly varies: from not quite 2 to > 45 years of age. In comparison, the average age when sporadic AML is diagnosed is 65 years of age.

The prognosis of familial AML appears to be good, with a 10-year overall survival (OS) rate of 67%, compared to sporadic AML, where the OS rate is 54% for a double CEBPA mutation and 29% for a single CEBPA mutation.

Even after AML has been treated successfully, patients with a familial CEBPA deficiency are still at risk of developing another leukemia. This is usually a distinct secondary leukemia with a more favorable prognosis and not a relapse.

Therapeutic Considerations

The treatment of AML in patients with a CEBPA mutation should be discussed thoroughly with the corresponding study center and – if possible – follow a study protocol, which generally involves cytarabine/anthracycline-based induction therapy followed by a cytarabine-based consolidation phase. Hematopoietic stem cell transplantation may be performed if there is no remission or secondary cases of disease occur. In principle, preemptive stem cell transplantation is also possible, such as in carriers of a CEBPA mutation before they develop leukemia for the first time. Due to the significant risks associated with a transplant, this is currently the subject of controversial debate.

Surveillance Recommendations

Surveillance Recommendations

Asymptomatic Mutation Carriers

  • Complete blood count every 6-12 months

  • Bone marrow puncture when there are anomalies or an abnormal blood count

Patients Suffering from AML

If the patient is suffering from AML, the approach follows the study protocol and must be discussed with the corresponding study center.

The recommendations following full remission in cases of CEBPA-associated familial AML are the same as those for sporadic AML:

  • Complete blood count every 1-3 months for two years and then every 3-6 months for up to 5 years

  • Bone marrow puncture in cases of cytopenia and/or an abnormal peripheral blood smear

Since leukemia may reoccur after a prolonged period of time, it is recommended that patients with CEBPA-associated familial AML undergo preventive medical checkups for the rest of their lives.

Additional Information

Open Clinical Trials / Registries

Support Groups

Unfortunately, we are as yet unaware of any existing support groups for patients with CEBPA deficiency. We will add new information as it becomes available.