• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2014.

Cover of GeneReviews®

GeneReviews® [Internet].

Show details

Familial Acute Myeloid Leukemia (AML) with Mutated CEBPA

Synonym: CEBPA-Dependent Familial Acute Myeloid Leukemia

, MD, JD and , MD.

Author Information
, MD, JD
Attending Pathologist, Department of Molecular Pathology
Cleveland Clinic
Cleveland, Ohio
, MD
Professor, Division of Hematology Oncology
Comprehensive Cancer Center
Ohio State University
Columbus, Ohio

Initial Posting: .

Summary

Disease characteristics. Familial acute myeloid leukemia (AML) with mutated CEBPA is defined as AML in which a germline CEBPA mutation is present in a family in which multiple individuals have AML. In contrast, sporadic AML with mutated CEBPA is defined as AML in which a CEBPA mutation is identified in somatic (i.e., leukemic) cells but not in germline (i.e., non-leukemic) cells. Too few persons with familial AML with mutated CEBPA have been reported to be certain about the natural history of the disease. The age of onset of familial AML with mutated CEBPA appears to be earlier than sporadic AML; disease onset has been reported in persons as young as age four years and older than age 50 years. The prognosis of individuals with familial AML with mutated CEBPA appears to be favorable (~50%-65% overall survival) compared to the ~25%-40% overall survival of those who have normal karyotype AML but no germline CEPBA mutation. Individuals with familial AML with mutated CEBPA who have been cured of their initial disease may be at greater risk of developing additional malignant clones than persons with sporadic disease.

Diagnosis/testing. CEBPA mutations are found in the leukemic cells of approximately 9% of persons with AML, including 15%-18% of persons with normal-karyotype AML; however, few of these individuals have a germline mutation. Detection of a germline CEBPA mutation in a specimen that contains only non-leukemic cells from an individual with AML or detection of a germline CEBPA mutation in a member of a pedigree in which more than one family member has had AML or myelodysplastic syndrome (MDS) establishes the diagnosis of familial AML with mutated CEBPA.

Management. Treatment of manifestations: Treatment usually includes cytarabine/anthracycline-based induction and cytarabine-based consolidation chemotherapy with or without hematopoietic stem cell transplantation (HSCT). Whenever possible, persons with AML should be treated as part of a clinical trial protocol.

Prevention of secondary complications: Similar to that for other types of AML (i.e., administration of blood products such as red blood cell and platelet transfusions as needed; treatment of infections with antibiotics; and use of prophylactic antibiotics and anti-fungal agents during periods of severe neutropenia).

Surveillance: Similar to that for other forms of AML. Because of the possible lifelong increased risk of leukemia in persons with familial AML with mutated CEBPA who are cured of their initial disease, additional (possibly lifelong) surveillance may be warranted.

Genetic counseling. Familial AML with mutated CEBPA is inherited in an autosomal dominant manner. The proportion of cases caused by a de novo germline mutation is unknown; currently, all seven reported affected individuals have had an affected parent. Each child of an affected individual has a 50% chance of inheriting the germline mutation. If the disease-causing mutation has been identified in an affected family member, prenatal testing for at-risk pregnancies is possible through laboratories offering either prenatal testing for the gene of interest or custom testing. Requests for prenatal testing for conditions that do not affect intellect and have treatment available are not common.

Diagnosis

Clinical Diagnosis

A provisional diagnostic category of “AML with mutated CEBPA” has been set forth in the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues [Arber et al 2008, Owen et al 2008, Renneville et al 2008]. Although the WHO category is primarily intended to classify AML with acquired (somatic) mutations in CEBPA, this category also includes inherited (germline) mutations in CEBPA, which are considerably rarer. Note: Most persons with familial or acquired AML with mutated CEBPA have “normal karyotype AML” (i.e., AML in which cytogenetic studies of leukemia cells are normal).

For this GeneReview, the following definitions are used:

Familial acute myeloid leukemia (AML) with mutated CEBPA is defined as AML in which a germline CEBPA mutation is present in an affected individual in a pedigree with familial AML. The diagnosis of familial AML with mutated CEBPA is established by either of the following:

  • Detection of a germline CEBPA mutation in a specimen that contains only non-leukemic cells from an individual with AML
  • Detection of a germline CEBPA mutation in a member of a pedigree in which more than one family member has been affected with AML or myelodysplastic syndrome (MDS)

Note: Most individuals with a germline CEBPA mutation appear to have a positive family history of AML.

Sporadic AML with mutated CEBPA is defined as AML in which a CEBPA mutation(s) is identified in somatic (i.e., leukemic) cells but a CEBPA mutation is not present in germline (i.e., non-leukemic) cells.

Molecular Genetic Testing

Gene. CEBPA is the only gene known to be associated with familial AML with mutated CEBPA.

CEBPA mutations are found in the leukemic cells of approximately 9% of persons with AML, including 15%-18% of persons with normal-karyotype AML [Arber et al 2008, Renneville et al 2008]. However, few of these individuals have a germline CEBPA mutation.

Clinical testing

Note: (1) Testing for a germline mutation should not be performed on blood or bone marrow during active AML. Testing a non-involved specimen, such as cells obtained by buccal swab, is imperative. (2) During clinical remission of AML when the percentage of leukemic cells in blood and bone marrow is very low, a CEBPA mutation that is present only in leukemic cells becomes undetectable. Because the lower limit of detection of a mutant allele by direct sequence analysis is approximately 20% allele proportion, relatively small numbers of morphologically undetectable leukemic cells are not expected to produce false positive results for a germline mutation. Therefore, during remission, testing for germline mutations may be performed with caution on a blood sample, although a buccal swab is preferred.

Table 1. Summary of Molecular Genetic Testing Used to Detect Germline Mutations in Familial Acute AML with Mutated CEBPA

Gene SymbolTest MethodMutations DetectedMutation Detection Frequency by Test Method 1
CEBPASequence analysis of non-leukemic cellsGermline sequence variants in the coding region 2>99% 3

1. The ability of the test method used to detect a mutation that is present in the indicated gene

2. Examples of mutations detected by sequence analysis may include small intragenic deletions/insertions and missense, nonsense, and splice-site mutations; typically, exonic or whole-gene deletions/duplications are not detected.

3. The analytic sensitivity of sequence analysis is expected to be >99% for mutations within the coding region. Sequencing of the coding region does not detect putative partial or complete gene deletions or mutations in promoter regions. However, no such germline mutations causing familial AML with mutated CEBPA have been reported to date.

Interpretation of test results. Because all seven pedigrees reported with familial AML with mutated CEBPA had a germline mutation that disrupted or predicted a disruption of the N-terminal region of the CEBPA protein, germline variants with similar functional consequences appear to be most common in pedigrees with familial AML with mutated CEBPA.

For issues to consider in interpretation of sequence analysis results, click here.

Testing Strategy

To confirm/establish the diagnosis of familial AML with mutated CEBPA in a proband. Testing for germline CEPBA mutations is recommended in:

  • Persons with AML with mutated CEBPA in leukemic cells who have a family history of AML or who have developed AML at an early age;
  • Persons with AML who have a family history of AML, but who have not had CEBPA testing on their leukemic cells.

Prenatal diagnosis and preimplantation genetic diagnosis (PGD) for at-risk pregnancies require prior identification of the germline mutation in the family.

Clinical Description

Natural History

Germline CEBPA mutations were only recently discovered as the cause of familial acute myeloid leukemia (AML) with mutated CEBPA and only a limited number of cases have been reported to date; therefore, the true range of clinical phenotypes of this disorder is unknown [Pabst & Mueller 2009]. At this point inherited CEBPA mutations have only been associated with pure familial (i.e., nonsyndromic) AML, which is AML that is not part of broader genetic syndrome such as Fanconi anemia, Bloom syndrome, or Down syndrome. However, this understanding of familial AML with mutated CEBPA could change in the future as more pedigrees are identified.

The age of onset of familial AML with mutated CEBPA is highly variable, but appears to be earlier than sporadic AML. Disease onset has been reported in persons as young as age four years and older than age 50 years [Pabst et al 2008, Renneville et al 2009]. By contrast, the median age at diagnosis of persons with sporadic AML is 65 years.

From an analysis of the seven reported pedigrees with familial AML with mutated CEBPA, it appears that the disease behaves similarly to sporadic AML with mutated CEBPA.

Too few patients with familial AML with mutated CEBPA have been reported to know the natural history of the disease; however, the prognosis of individuals with familial AML with mutated CEBPA appears to be favorable (~50%-65% overall survival, compared to the ~25%-40% overall survival of those who have normal karyotype AML but no germline CEPBA mutation). These data are predominantly from persons age 60 years and younger who received standard therapies [Preudhomme et al 2002, Frohling et al 2004, Bienz et al 2005, Marcucci et al 2008]. The positive prognosis associated with AML with mutated CEBPA (familial or sporadic) may be confined to persons with biallelic CEBPA mutations [Pabst et al 2009, Wouters et al 2009, Dufour et al 2010, Green et al 2010].

Individuals with familial AML with mutated CEBPA who have been cured of their initial disease may be at greater risk of developing additional malignant clones than persons who do not have germline CEBPA mutations (i.e., those with sporadic disease) [Pabst et al 2008]. This conjecture is based on the observation that individuals who relapse have somatic CEBPA mutations that differ from those observed in the original leukemia. This phenomenon has not been reported in individuals with sporadic AML with mutated CEBPA who relapse.

Pathologic features of leukemic cells in AML with mutated CEBPA (familial or sporadic) include:

  • Normal karyotype
  • A preponderance 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
  • Many Auer rods seen 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

Genotype-Phenotype Correlations

No specific genotype-phenotype correlations have been described in familial AML with mutated CEBPA.

Penetrance

Analysis of the seven pedigrees reported to date with a probable disease-related germline CEBPA mutation suggests that germline CEBPA mutations exhibit complete or nearly complete penetrance for the development of AML [Owen et al 2008, Renneville et al 2008, Pabst et al 2009].

Anticipation

Anticipation has not been reported in familial AML with mutated CEBPA.

Nomenclature

Familial AML with mutated CEBPA is a form of “pure familial AML” (also known as “nonsyndromic familial AML”), meaning that AML is the sole manifestation of the disorder.

Prior to the discovery of germline CEBPA mutations as a cause of nonsyndromic familial AML, pedigrees with familial AML with mutated CEBPA were classified with other types of familial AML of unknown etiology.

Prevalence

Familial AML with mutated CEBPA is very rare, with only seven pedigrees reported as of this writing [Smith et al 2004, Sellick et al 2005, Corbacioglu et al 2007, Pabst et al 2008, Renneville et al 2009, Nanri et al 2010].

In the study of Pabst et al [2008], 18 of 187 consecutive individuals presenting with AML had AML with mutated CEBPA. Two of these individuals had a germline CEBPA mutation; both had a family history of AML.

Differential Diagnosis

The differential diagnosis for familial acute myeloid leukemia (AML) with mutated CEBPA includes:

  • Sporadic AML with CEBPA mutations
  • AML secondary to environmental exposures (e.g., benzene, radiation, chemotherapy) *
  • Sporadic AML with more than one affected family member *

    Note: The more affected individuals in a family (and the closer the relationships) the greater the likelihood of a common cause.
  • RUNX1-mediated familial AML
  • Familial AML in association with monosomy 7 (see Familial Mosaic Monosomy 7 Syndrome)
  • Familial AML caused by as-yet undiscovered genes

* AML is a relatively rare disease (~13,300 cases/year in the US); therefore, pedigrees with more than one case of AML could have a heritable predisposition or a common exposure [Owen et al 2008].

Management

Evaluations Following Initial Diagnosis

General evaluation of individuals presenting with signs and symptoms of acute myeloid leukemia (AML) commonly includes:

  • History and physical examination
  • Complete blood count (CBC) with differential and review of peripheral blood smear
  • Platelet count
  • Chemistry profile
  • Pathologic bone marrow evaluation
  • Flow cytometry
  • Cytochemistries
  • Cytogenetic studies in leukemic cells
  • In those with normal-karyotype AML, testing of leukemic cells for mutations in:
    • FLT3 (encoding fms-related tyrosine kinase 3)
    • NPM1 (encoding nucleophosmin)
    • CEBPA

To establish the extent of disease and needs of an individual newly diagnosed with AML, the following evaluations are recommended:

  • Cardiac scan in patients with a personal history of – or signs and symptoms suspicious for – heart disease and in those who have received previous anthracycline therapy
  • HLA typing in anticipation of hematopoietic stem cell transplantation (HSCT)
  • Lumbar puncture (LP) if symptoms suggest central nervous system disease. The timing of LP in AML is controversial.

Treatment of Manifestations

Management of familial AML with mutated CEBPA does not differ from that of sporadic AML with mutated CEBPA [National Comprehensive Cancer Network 2009, Döhner et al 2010].

Treatment usually includes cytarabine/anthracycline-based induction and cytarabine-based consolidation chemotherapy with or without hematopoietic stem cell transplantation (HSCT) according to clinical, cytogenetic, and molecular risk. Specific treatment strategies are based on characteristics of the individual patient, response to chemotherapy, treatment setting, and protocol (if the patient is enrolled in a clinical trial). Note: Whenever possible, persons with AML should be treated as part of a clinical trial protocol.

Relapses are treated with cytabine-based salvage chemotherapy followed by allogeneic HSCT if a donor is available and if cure is the intent of treatment.

Prevention of Secondary Complications

Prevention of secondary complications is similar to that for other types of AML.

  • Supportive care includes blood products such as red blood cell and platelet transfusions as needed and treatment of infections with antibiotics.
  • Prophylactic antibiotics and antifungal agents are administered during periods of severe neutropenia including the consolidation and post-transplantation periods [National Comprehensive Cancer Network 2009].

Surveillance

Surveillance for familial AML with mutated CEBPA is similar to that for other forms of AML. There are no generally accepted minimal residual disease markers in AML with mutated CEBPA or in most other AML subtypes, including those with normal karyotypes. Patients with familial AML with mutated CEBPA who are cured of their initial disease may have an increased lifelong risk of leukemia [Pabst et al 2009]; therefore, additional surveillance, possibly lifelong, may be warranted.

Patients are monitored and evaluated in accordance with administered treatment, clinical course, symptoms, and protocol, if enrolled in clinical trials. When complete remission is achieved and intensification therapy is complete, patients are monitored with:

  • CBC and platelet counts every one to three months for two years with the frequency decreasing to every three to six months for up to five years;
  • Bone marrow aspiration when cytopenia and/or an abnormal peripheral blood smear are present.

Note: The use of flow cytometry for minimal residual disease monitoring is controversial.

Evaluation of Relatives at Risk

See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.

Therapies Under Investigation

Search Clinical Trials.gov for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Genetic Counseling

Genetic counseling is the process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders to help them make informed medical and personal decisions. The following section deals with genetic risk assessment and the use of family history and genetic testing to clarify genetic status for family members. This section is not meant to address all personal, cultural, or ethical issues that individuals may face or to substitute for consultation with a genetics professional. —ED.

Mode of Inheritance

Familial AML with mutated CEBPA is inherited in an autosomal dominant manner.

Risk to Family Members

Parents of a proband

  • Currently, all reported individuals diagnosed with familial AML with mutated CEBPA have had an affected parent.
  • A proband with familial AML with mutated CEBPA may have the disorder as the result of a new germline mutation. The proportion of cases caused by de novo germline mutations is unknown.
  • Recommendations for the evaluation of parents of a proband with an apparent de novo germline mutation include evaluation of the complete blood count (CBC), hematologic indices, and peripheral blood smear and testing for the germline CEBPA mutation identified in the proband.
  • An apparently negative family history cannot be confirmed until appropriate evaluations have been performed.

Note: (1) Although all reported individuals diagnosed with familial AML with mutated CEBPA have had an affected parent, the family history may appear to be negative because of incomplete penetrance in family members, early death of the parent before the onset of symptoms, or late onset of the disease in the affected parent. (2) If the parent is the individual in whom the germline mutation first occurred s/he could potentially have somatic mosaicism for the germline mutation.

Sibs of a proband

Offspring of a proband. Each child of an individual with familial AML with mutated CEBPA has a 50% chance of inheriting the germline mutation.

Other family members. The risk to other family members depends on the status of the proband's parents. If a parent is affected and/or has the germline mutation, his or her family members may be at risk.

Related Genetic Counseling Issues

Considerations in families with an apparent de novo germline mutation. When neither parent of a proband with an autosomal dominant condition has clinical evidence of the disorder, it is likely that the proband has a de novo germline mutation or the parent has reduced penetrance for a germline mutation. However, possible non-medical explanations including alternate paternity or maternity (e.g., with assisted reproduction) or undisclosed adoption could also be explored.

Family planning

  • The optimal time for determination of genetic risk in offspring of persons with known familial AML with mutated CEBPA is before pregnancy. Because familial AML with mutated CEBPA is rare, general screening of individuals with AML or a family history of AML for CEBPA germline mutations is not recommended for family planning purposes unless familial AML with mutated CEBPA is suspected.
  • It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are affected or at risk.

DNA banking is the storage of DNA (typically extracted from white blood cells) for possible future use. Because it is likely that testing methodology and our understanding of genes, mutations, and diseases will improve in the future, consideration should be given to banking DNA of affected individuals.

In AML generally, tissue banking that is performed for future research purposes should include banking of DNA, RNA, protein lysates, and cryopreserved cells.

Prenatal Testing

If the disease-causing mutation has been identified in an affected family member, prenatal testing for at-risk pregnancies is possible through laboratories offering either prenatal testing for the gene of interest or custom testing.

Requests for prenatal testing for conditions which (like familial AML with mutated CEBPA) do not affect intellect and have treatment available are not common. Differences in perspective may exist among medical professionals and within families regarding the use of prenatal testing, particularly if the testing is being considered for the purpose of pregnancy termination rather than early diagnosis. Although decisions about prenatal testing are the choice of the parents, discussion of these issues is appropriate.

Preimplantation genetic diagnosis (PGD) may be an option for some families in which the disease-causing germline mutation has been identified.

Resources

GeneReviews staff has selected the following disease-specific and/or umbrella support organizations and/or registries for the benefit of individuals with this disorder and their families. GeneReviews is not responsible for the information provided by other organizations. For information on selection criteria, click here.

No specific resources for Familial Acute Myeloid Leukemia (AML) with Mutated CEBPA have been identified by GeneReviews staff.

Molecular Genetics

Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED.

Table A. Familial Acute Myeloid Leukemia (AML) with Mutated CEBPA: Genes and Databases

Gene SymbolChromosomal LocusProtein NameHGMD
CEBPA19q13​.11CCAAT/enhancer-binding protein alphaCEBPA

Data are compiled from the following standard references: gene symbol from HGNC; chromosomal locus, locus name, critical region, complementation group from OMIM; protein name from UniProt. For a description of databases (Locus Specific, HGMD) to which links are provided, click here.

Table B. OMIM Entries for Familial Acute Myeloid Leukemia (AML) with Mutated CEBPA (View All in OMIM)

116897CCAAT/ENHANCER-BINDING PROTEIN, ALPHA; CEBPA
601626LEUKEMIA, ACUTE MYELOID; AML

CEBPA encodes the CCAAT/enhancer-binding protein alpha (CEBPA), a transcription factor that plays a key role in granulocyte development. A detailed review of the role of CEBPA in human cancer has recently been published [Koschmieder et al 2009]. The role of mutation of CEBPA in the formation of AML is not well understood, and is a source of ongoing research [Pabst & Mueller 2007, Pabst & Mueller 2009].

Normal germline allelic variants. CEBPA is a single-exon gene; the primary CEBPA transcript (NM_004364.3) is 2591 bp. There are two in-frame AUG start codons (codon 1 and codon 120) that result in two CEBPA protein isoforms. A few normal allelic variants in the CEBPA coding region have been reported (see Table 2).

Pathologic germline allelic variants. The germline mutations identified to date are listed in Table 2; the c.217_218insC variant has been reported in two pedigrees. Thus far, reported germline mutations have been small insertions/deletions that result in frameshifts in CEBPA regions that encode the N-terminal region of the protein and predict premature termination of synthesis of the full-length CEBPA protein (see Normal gene product).

Table 2. Selected CEBPA Germline Allelic Variants

Class of Variant AlleleDNA Nucleotide Change
(Alias 1)
Protein Amino Acid ChangeReference Sequences
Normalc.754G>Tp.Ala252SerNM_004364​.3
NP_004355​.2
c.713C>Ap.Ala238Glu
c.690G>Tp.Thr230Thr
Pathologicc.68delCp.Pro23Argfs*137
c.68dupCp.His24Alafs*84
c.141delCp.Ala48Profs*112
c.198_201dupCTACp.Ile68Leufs*41
c.318_319dupTp.Asp107Valfs*54
c.217_218insC 2
(217insC)
p.Phe73Serfs*35

Note on variant classification: Variants listed in the table have been provided by the author(s). GeneReviews staff have not independently verified the classification of variants.

Note on nomenclature: GeneReviews follows the standard naming conventions of the Human Genome Variation Society (www​.hgvs.org). See Quick Reference for an explanation of nomenclature.

1. Variant designation that does not conform to current naming conventions

2. Reported in two pedigrees

Normal gene product. The primary CEBPA transcript (NM_004364.3) encodes the CCAAT/enhancer binding protein alpha (C/EBP alpha), which is a transcription factor of a 358-amino-acid, 42-kd protein (reference sequence NP_004355). The full-length 42-kd protein contains two distinct N-terminal transactivation domains (mediate contact with transcriptional apparatus), a C-terminal basic region (DNA-binding), and a leucine zipper for dimerization.

An alternative shorter transcript occurs when AUG codon 120 is used as an alternative start site. This shorter transcript encodes a 30-kd protein isoform that lacks the first transactivation domain and impairs interaction with the transcriptional apparatus. The C-terminal domains are intact [Pabst & Mueller 2007, Pabst & Mueller 2009]. Evidence from cell culture identified CEBPA protein as a tumor suppressor and an inhibitor of cell proliferation. Evidence from mouse models is consistent with the tumor suppressor activity being in the 42-kd isoform and transformation in the absence of 42 kd is mediated by a 30-kd isoform which has a dominant-negative effect leading to the formation of progenitors prone to deregulated proliferation and transformation [abstracted from Pabst & Mueller 2009].

Abnormal gene product. The reported germline pathologic mutations in CEBPA (Table 2) occur before codon 120 and cause/predict premature termination of synthesis of the full-length CEBPA protein, with preservation of the 30-kd isoform. The 30-kd protein is believed to inhibit the action of the normal 42-kd protein encoded by the remaining normal allele in a dominant-negative manner.

Note about somatic mutations in familial AML with CEBPA mutations. The leukemic cells of most individuals with familial AML with mutated CEBPA are compound heterozygous. In addition to the germline mutation described above in the N-terminal region (see Pathologic germline allelic variants), the leukemic cells commonly acquire somatic C-terminal in frame mutation(s). C-terminal in-frame mutations disrupt the basic region and leucine zipper, impairing DNA binding as well as homo- and heterodimerization with other CEBP proteins and/or DNA binding [Pabst & Mueller 2007, Pabst & Mueller 2009].

The leukemic cells of persons with sporadic AML with CEBPA mutations have similar N-terminal and C-terminal mutations. In 50%-75% of all persons with AML with mutated CEBPA, biallelic CEBPA mutations are identified.

References

Literature Cited

  1. Arber DA, Brunning RD, Le Beau MM, Falini B, Vardiman JW, Porwit A, Thiele J, Bloomfield CD. Acute myeloid leukaemia with recurrent genetic abnormalities. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW, eds. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4 ed. Lyon, France: WHO Press; 2008:110-23.
  2. Bienz M, Ludwig M, Mueller BU, Leibundgut E, Ratschiller D, Solenthaler M, Fey MF, Pabst T. Risk Assessment in Patients with Acute Myeloid Leukemia and a Normal Karyotype. Clin Cancer Res. 2005;11:1416–24. [PubMed: 15746041]
  3. Corbacioglu A, Frohling S, Mendla C, Eiwen K, Habdank M, Döhner H, Schlenk RF, Dohner K. CEBPA Germline Mutation Screening in Cytogenetically Normal Acute Myeloid Leukemia with Somatically Acquired CEBPA Mutations. Blood. 2007;110:363a.
  4. Döhner H, Estey EH, Amadori S, Appelbaum FR, Büchner T, Burnett AK, Dombret H, Fenaux P, Grimwade D, Larson RA, Lo-Coco F, Naoe T, Niederwieser D, Ossenkoppele GJ, Sanz MA, Sierra J, Tallman MS, Löwenberg B, Bloomfield CD. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2010;115:453–74. [PubMed: 19880497]
  5. Dufour A, Schneider F, Metzeler KH, Hoster E, Schneider S, Zellmeier E, Benthaus T, Sauerland M, Berdel WE, Buchner T, Wormann B, Braess J, Hiddemann W, Bohlander SK, Spiekermann K. Acute myeloid leukemia With biallelic CEBPA gene mutations and normal karyotype represents a distinct genetic entity associated with a favorable clinical outcome. J Clin Oncol. 2010;28:570–77. [PubMed: 20038735]
  6. Frohling S, Schlenk RF, Stolze I, Bihlmayr J, Benner A, Kreitmeier S, Tobis K, Döhner H, Dohner K. CEBPA Mutations in Younger Adults With Acute Myeloid Leukemia and Normal Cytogenetics: Prognostic Relevance and Analysis of Cooperating Mutations. J Clin Oncol. 2004;22:624–33. [PubMed: 14726504]
  7. Green CL, Koo KK, Hills RK, Burnett AK, Linch DC, Gale RE. Prognostic Significance of CEBPA Mutations in a Large Cohort of Younger Adult Patients With Acute Myeloid Leukemia: Impact of Double CEBPA Mutations and the Interaction With FLT3 and NPM1 Mutations. J Clin Oncol. 2010;28:2739–47. [PubMed: 20439648]
  8. Koschmieder S, Balazs H, Levantini E, Tenen DG. Dysregulation of the C/EBPα Differentiation Pathway in Human Cancer. J Clin Oncol. 2009;27:619–28. [PMC free article: PMC2645860] [PubMed: 19075268]
  9. Marcucci G, Maharry K, Radmacher MD, Mrozek K, Vukosavljevic T, Paschka P, Whitman SP, Langer C, Baldus CD, Liu C-G, Ruppert AS, Powell BL, Carroll AJ, Caligiuri MA, Kolitz JE, Larson RA, Bloomfield CD. Prognostic significance of, and gene and microRNA expression signatures associated with, CEBPA mutations in cytogenetically normal acute myeloid leukemia with high-risk molecular features: a cancer and leukemia group B study. J Clin Oncol. 2008;26:5078–87. [PMC free article: PMC2652095] [PubMed: 18809607]
  10. Nanri T, Uike N, Kawakita T, Iwanaga E, Hoshino K, Mitsuya H, Asou N. A family harboring a Germ-Line N-Terminal C/EBPα Mutation and Development of Acute Myeloblastic Leukemia with an Additional Somatic C-Terminal C/EBPα Mutation. Genes Chromosomes Cancer. 2010;49:237–41. [PubMed: 19953636]
  11. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology™. Available online. 2009. Accessed 2-20-13.
  12. Owen C, Barnett M, Fitzgibbon J. Familial myelodysplasia and acute myeloid leukaemia--a review. Br J Haematol. 2008;140:123–32. [PubMed: 18173751]
  13. Pabst T, Eyholzer M, Fos J, Mueller BU. Heterogeneity within AML with CEBPA mutations; only CEBPA double mutations, but not single CEBPA mutations are associated with favourable prognosis. Br J Cancer. 2009;100:1343–46. [PMC free article: PMC2676545] [PubMed: 19277035]
  14. Pabst T, Eyholzer M, Haefliger S, Schardt J, Mueller BU. Somatic CEBPA mutations are a frequent second event in families with germline CEBPA mutations and familial acute myeloid leukemia. J Clin Oncol. 2008;26:5088–93. [PubMed: 18768433]
  15. Pabst T, Mueller BU. Transcriptional dysregulation during myeloid transformation in AML. Oncogene. 2007;26:6829–37. [PubMed: 17934489]
  16. Pabst T, Mueller BU. Complexity of CEBPA Dysregulation in Human Acute Myeloid Leukemia. Clin Cancer Res. 2009;15:5303–7. [PubMed: 19706798]
  17. Preudhomme C, Sagot C, Boissel N, Cayuela JM, Tigaud I, de Botton S, Thomas X, Raffoux E, Lamandin C, Castaigne S, Fenaux P, Dombret H. ALFA Group; Favorable prognostic significance of CEBPA mutations in patients with de novo acute myeloid leukemia: a study from the Acute Leukemia French Association (ALFA). Blood. 2002;100:2717–23. [PubMed: 12351377]
  18. Renneville A, Mialou V, Philippe N, Kagialis-Girard S, Biggio V, Zabot MT, Thomas X, Bertrand Y, Preudhomme C. Another pedigree with familial acute myeloid leukemia and germline CEBPA mutation. Leukemia. 2009;23:804–6. [PubMed: 18946494]
  19. Renneville A, Roumier C, Biggio V, Nibourel O, Boissel N, Fenaux P, Preudhomme C. Cooperating gene mutations in acute myeloid leukemia: a review of the literature. Leukemia. 2008;22:915–31. [PubMed: 18288131]
  20. Sellick GS, Spendlove HE, Catovsky D, Pritchard-Jones K, Houlston RS. Further evidence that germline CEBPA mutations cause dominant inheritance of acute myeloid leukemia. Leukemia. 2005;19:1276–8. [PubMed: 15902292]
  21. Smith ML, Cavenagh JD, Lister TA, Fitzgibbon J. Mutation of CEBPA in Familial Acute Myeloid Leukemia. N Engl J Med. 2004;351:2403–7. [PubMed: 15575056]
  22. Wouters BJ, Lowenberg B, Erpelinck-Verschueren CAJ, van Putten WLJ, Valk PJM, Delwel R. Double CEBPA mutations, but not single CEBPA mutations define a subgroup of acute myeloid leukemia with a distinctive gene expression profile that is uniquely associated with a favorable outcome. Blood. 2009;113:3088–91. [PMC free article: PMC2662648] [PubMed: 19171880]

Chapter Notes

Revision History

  • 21 October 2010 (me) Review posted live
  • 30 December 2009 (rdk) Original submission
Copyright © 1993-2014, University of Washington, Seattle. All rights reserved.

For more information, see the GeneReviews Copyright Notice and Usage Disclaimer.

For questions regarding permissions: ude.wu@tssamda.

Bookshelf ID: NBK47457PMID: 20963938
PubReader format: click here to try

Views

  • PubReader
  • Print View
  • Cite this Page
  • Disable Glossary Links

Tests in GTR by Gene

Tests in GTR by Condition

Related information

  • MedGen
    Related information in MedGen
  • OMIM
    Related OMIM records
  • PMC
    PubMed Central citations
  • PubMed
    Links to pubmed
  • Gene
    Gene records cited in chapters on the NCBI bookshelf. Links are provided by the authors or the NCBI Bookshelf staff.

Related citations in PubMed

See reviews...See all...

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...