What is CEBPA deficiency?

CEBPA deficiency, or CEBPA-associated familial acute myeloid leukemia, is a leukemia predisposition syndrome caused by a mutation – or genetic change – in the CEBPA gene. Typically, there is early onset of acute myeloid leukemia (AML) in multiple family members.

How is CEBPA deficiency diagnosed?

Suspected Diagnosis

A CEBPA deficiency is suspected in the following persons:

  • People with AML who have close relatives who also suffer from AML

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

Genetic Diagnostics

The diagnosis of “familial CEBPA deficiency” is confirmed by detection of a mutation – or genetic change – in the CEBPA gene.

Additional Clinical Diagnostics (after the diagnosis has been made)

  • HLA typing with regard to possible stem cell transplantation

  • Additional extensive examinations are conducted if there is leukemia.

Human Genetics

  • Human genetic linkage analysis 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

What is the risk of cancer?

The risk of developing AML is very high: more than 80%. AML associated with familial CEBPA deficiency appears to have an earlier onset than sporadic, non-familial 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 for the familial form of AML appears to be better than that for sporadic AML. 67% of patients are still alive after 10 years.

Even after AML has been overcome, patients with familial CEBPA deficiency are still at risk of developing leukemia again.

What causes CEBPA deficiency?

CEBPA deficiency is caused by a mutation – or genetic change – in the CEBPA gene. This gene encodes for the C/EBPα protein, called a transcription factor, which plays a key role in the development of granulocytes, a specific type of white blood cell. Now if the CEBPA gene is in an altered form, the transcription factor can no longer function properly, resulting in the development of leukemia.

The CEBPA deficiency can be passed on by parents to their children. In these cases, it is inherited as an autosomal dominant disease.

Is there a treatment?

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. Treatment generally consists of chemotherapy. It may be worth considering stem cell transplantation if a relapse of leukemia fails to improve.

Performing stem cell transplantation in CEBPA mutation carriers before the first case of leukemia develops is currently controversial. While transplantation can be curative, it can also cause severe side effects.

Surveillance Recommendations for the Early Detection of Cancer

Surveillance Recommendations

Mutation carriers not suffering from AML

  • 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 with abnormal blood findings

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.

Self-Care and Support

What should I pay special attention to?

You should see a doctor as soon as you notice increased bleeding (e.g. nose or gum bleeding) or bruises. In addition, you should also go see a doctor right away if you are fatigued, feel sick, or have a fever, night sweats, pallor, frequent infections, or swollen lymph nodes. If you develop new anomalies or complaints, they should likewise be evaluated as soon as possible.

Support Groups and Additional Information

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.