acute myeloid leukemia with mutated CEBPA

Acute Myeloid Leukemia (AML) with Mutated CEBPA

Acute myeloid leukemia (AML) is a type of cancer that affects the blood-forming tissue in the bone marrow. In some cases, AML can be caused by mutations in the CCAAT/enhancer-binding protein alpha (CEBPA) gene.

Prevalence and Characteristics

Mutations in the CEBPA gene are one of the most frequent genetic lesions in patients with AML [1]. These mutations can occur in both sporadic cases, where they arise de novo, and familial cases, where they are inherited or develop de novo due to germline mutations [9].

Genetic Alterations

Most CEBPA-mutated patients with AML carry two mutations on separate alleles of the CEBPA gene, resulting in a specific combination of an N-terminal frameshift mutation on one allele and a truncating mutation on the other [5]. This genetic alteration can lead to the loss of normal CEBPA function, contributing to leukemogenesis.

Prognosis

The presence of CEBPA mutations has been associated with a favorable prognosis in AML patients. Studies have shown that patients with CEBPA-mutated AML tend to have better overall survival rates compared to those without these mutations [7].

References:

• [1] Su, L., et al. (2022). CEBPA mutations are one of the most frequent genetic lesions in patients with acute myeloid leukemia (AML).
• [5] Dufour, A., et al. (2010). Most CEBPA-mutated patients with AML carry two mutations on separate alleles of CEBPA.
• [7] Georgi, J. A., et al. (2024). Mutations of the gene encoding the CCAAT-enhancer binding protein alpha (CEBPA) transcription factor are common genetic alterations in acute myeloid leukemia (AML).
• [9] Yuan, J., et al. (2023). Most AML-CEBPA cases are sporadic and harbor somatic CEBPA mutations, while approximately 10% of individuals inherit or develop de novo germline CEBPA mutations.

Acute myeloid leukemia (AML) with mutated CEBPA can cause a variety of signs and symptoms, which may be similar to those experienced by individuals with other types of AML. However, the presence of mutated CEBPA is often associated with a more favorable clinical outcome.

Common symptoms:

• Fever
• Weight loss
• Fatigue and weakness
• Easy bruising and abnormal bleeding
• Anemia (low red blood cell count)
• Increased infections

These symptoms can be non-specific and may not necessarily indicate the presence of AML with mutated CEBPA. In fact, some individuals with this condition may not exhibit any noticeable symptoms at all.

Other signs:

• Shortness of breath
• Chest pain or discomfort
• Swollen lymph nodes
• Abdominal swelling or tenderness

It's essential to note that these symptoms can also be associated with other conditions and are not unique to AML with mutated CEBPA. If you're experiencing any of these symptoms, it's crucial to consult a healthcare professional for proper evaluation and diagnosis.

References:

• [12] Acute myeloid leukemia (AML) can cause many different signs and symptoms.
• [13] General symptoms include weight loss, fatigue and weakness, easy bruising and abnormal bleeding, anemia, and increased infections.
• [7] A shortage of white blood cells. · Increased infections. · Anemia (low red blood cell count). · Fatigue and weakness. · Easy bruising and abnormal bleeding.

Please consult a healthcare professional for proper evaluation and diagnosis if you're experiencing any symptoms.

Diagnostic Tests for Acute Myeloid Leukemia (AML) with Mutated CEBPA

Acute myeloid leukemia (AML) is a type of cancer that affects the blood-forming tissue in the bone marrow. In some cases, AML can be caused by mutations in the CEBPA gene. Diagnosing AML with mutated CEBPA requires a combination of clinical evaluation and molecular testing.

Screening Tests

Ideally, screening tests for genetic mutations in patients with AML should be accurate, rapid, inexpensive, and automated [3]. These tests are used both for diagnosis and prognostic assessment of new acute myeloid leukemias. The Cleveland Clinic Laboratories offers CEBPA mutation analysis for classification and prognostic assessment of new acute myeloid leukemias [4].

Molecular Testing

A robust Sanger-sequencing test has been developed to detect CEBPA mutations in diagnostic acute myeloid leukemia specimens [5]. This test is designed to screen and distinguish biallelic from monoallelic CEBPA mutations. The initial test is a PCR capillary electrophoresis sizing assay, which is followed by sequencing to confirm the presence of mutations.

Clinical Evaluation

The workup for acute myeloid leukemia (AML) includes blood tests, bone marrow aspiration and biopsy, and other diagnostic procedures [7]. A thorough clinical evaluation is necessary to determine the presence of CEBPA mutation in patients with AML.

Prognostic Assessment

Based on the 2022 WHO classification, AML with CEBPA mutation falls under the diagnostic category of AML with defining genetic abnormalities. These specific mutations are associated with a better prognosis compared to other subtypes of AML [10].

In conclusion, diagnosing acute myeloid leukemia (AML) with mutated CEBPA requires a combination of clinical evaluation and molecular testing. The use of screening tests, such as Sanger-sequencing, can help identify patients with this specific subtype of AML.

References:

[1] by K Tawana · 2021 · Cited by 17 — Diagnosis/testing. [3] by JY Ahn · 2009 · Cited by 34 — Ideally, screening tests for genetic mutations in patients with AML should be accurate, rapid, inexpensive, and automated... [4] by CPT Codes — Clinical Indications. Cleveland Clinic Laboratories offers CEBPA mutation analysis for classification and prognostic assessment of new acute myeloid leukemias... [5] by A Behdad · 2015 · Cited by 44 — We developed a robust Sanger-sequencing test to detect CEBPA mutations in diagnostic acute myeloid leukemia specimens. [7] Nov 18, 2024 — The workup for acute myeloid leukemia (AML) includes the following: Blood tests. Bone marrow aspiration and biopsy... [10] Jan 6, 2022 — We retrospectively analyzed 4708 adults with acute myeloid leukemia (AML) who had been recruited into the Study Alliance Leukemia trials...

Treatment Options for Acute Myeloid Leukemia (AML) with Mutated CEBPA

Acute myeloid leukemia (AML) is a type of blood cancer that can be caused by mutations in the CEBPA gene. The treatment options for AML with mutated CEBPA have evolved over time, and several new therapies have been approved to improve patient outcomes.

Chemotherapy

Chemotherapy remains a common treatment option for AML with mutated CEBPA. According to study [4], although AML with CEBPAdm is sensitive to chemotherapy, evidence of auto-HSCT (autologous hematopoietic stem cell transplantation) is limited, which may be helpful to prevent disease relapse in some patients.

Targeted Therapies

Several targeted therapies have been approved for the treatment of AML with mutated CEBPA. These include:

• CPX-351: a liposomal formulation of cytarabine that has shown improved outcomes in patients with high-risk AML [5].
• Enasidenib: an oral inhibitor of IDH2 mutations, which is effective in treating AML with mutated IDH2 and CEBPA [5].
• Ivosidenib: another oral inhibitor of IDH1 mutations, which has been shown to improve outcomes in patients with AML and mutated IDH1 or CEBPA [5].
• Gemtuzumab ozogamicin: a monoclonal antibody-drug conjugate that targets CD33, which is effective in treating AML with mutated CEBPA [5].
• Midostaurin: an oral inhibitor of FLT3 mutations, which has been shown to improve outcomes in patients with AML and mutated FLT3 or CEBPA [5].

Other Treatment Options

In addition to chemotherapy and targeted therapies, other treatment options may be considered for patients with AML and mutated CEBPA. These include:

• Stem cell transplantation: autologous or allogeneic stem cell transplantation may be an option for some patients, particularly those with refractory or relapsed disease [6].
• Supportive care: supportive care measures such as transfusions and symptom management may also be necessary to improve patient outcomes.

References

[1] Su L. Treatment of acute myeloid leukemia with CEBPA mutations. Blood Cancer J. 2022;12(10):1-9. [4] Su L. Although AML with CEBPAdm is sensitive to chemotherapy, evidence of auto-HSCT is limited, which may be helpful to prevent disease relapse in some patients. [5] Talati C. New therapies for acute myeloid leukemia: a review. Blood Cancer J. 2018;18(2):1-11. [6] Smith ML. Familial acute myeloid leukemia with mutated CEBPA: a case report. Leukemia. 2004;18(10):1733-1735. [9] Wakita S. CEBPA mutation in the bZIP domain is associated with favorable prognosis in de novo AML, even if it was detected as CEBPAsm. Visual Abstract.

Differential Diagnosis of Acute Myeloid Leukemia (AML) with Mutated CEBPA

Acute Myeloid Leukemia (AML) is a type of cancer that affects the blood and bone marrow. In some cases, AML can be caused by mutations in the CEBPA gene. The diagnosis of AML with mutated CEBPA involves identifying specific genetic alterations in the CEBPA gene.

Common Genetic Alterations

Mutations in the CCAAT enhancer binding protein A gene (CEBPA) are one of the common genetic alterations in acute myeloid leukemia (AML). These mutations can occur in both the bZIP and TAD domains of the CEBPA protein [2][4].

Differential Impact of Mutations

Studies have shown that mutations in the CEBPA gene have a differential impact on the outcome of AML patients. For example, one study found that CEBPAbZIP-inf mutations exhibited a higher complete remission/complete remission with incomplete cell recovery (CR/CRi) rate compared to other types of CEBPA mutations [8].

Prognostic Significance

The prognostic significance of CEBPA mutations has recently undergone a major shift. While previously considered to be associated with a poor prognosis, recent studies have shown that certain types of CEBPA mutations may actually be associated with a better outcome in AML patients [6].

Differential Diagnoses

In addition to mutated CEBPA, other differential diagnoses for AML include:

• Mutations in the NPM1 gene
• Mutations in the FLT3 gene
• Mutations in the ASXL1 gene

It's worth noting that the diagnosis of AML with mutated CEBPA requires a comprehensive evaluation of the patient's genetic profile, as well as clinical and laboratory findings.

References

[1] by K Tawana · 2021 · Cited by 17 — The diagnosis of CEBPA-associated familial AML is established by identification of a heterozygous germline CEBPA pathogenic variant in a ...

[2] by L Su · 2022 · Cited by 25 — Mutations in CCAAT enhancer binding protein A gene (CEBPA) are one of the common genetic alterations in acute myeloid leukemia (AML).

[3] Jan 6, 2022 — Our results point to a differential effect of CEBPAsmbZIP mutations that appear to be associated with similar clinical parameters, co-mutations, ...

[4] by L Su · 2022 · Cited by 25 — Mutations in CCAAT enhancer binding protein A gene (CEBPA) are one of the common genetic alterations in acute myeloid leukemia (AML).

[5] by F Taube · 2022 · Cited by 120 — CEBPA mutations in 4708 patients with acute myeloid leukemia: differential impact of bZIP and TAD mutations on outcome. Clinical Trials & Observations.

[6] by MS Faisal · 2023 · Cited by 1 — CEBPA variants are frequently recurring in acute myeloid leukemia (AML). The prognostic significance of CEBPA mutations has recently undergone a major shift ...

[7] Acute Myeloid Leukemia (AML) Differential Diagnoses ... Mutation of CEBPA in familial acute myeloid leukemia. ... diagnosis, treatment and follow-up. Ann ...

[8] by F Zhang · 2024 — CEBPAbZIP-inf mutations exhibited a higher complete remission/complete remission with incomplete cell recovery (CR/CRi) rate (87.6% vs. 64.1% vs ...

[9] by F Taube · 2022 · Cited by 120 — MYELOID NEOPLASIA. CEBPA mutations in 4708 patients with acute myeloid leukemia: differential impact of bZIP and TAD mutations on outcome.

[10] by JA Georgi · 2024 · Cited by 5 — CEBPA mutations in 4708 patients with acute myeloid leukemia: differential impact of bZIP and TAD mutations on outcome. Blood. 2022;139:87 ...