acute myeloid leukemia with t(6;9) (p23;q34.1)

Acute Myeloid Leukemia with t(6;9)(p23;q34.1)

Acute myeloid leukemia (AML) with a translocation between chromosomes 6 and 9, specifically at the breakpoints p23 and q34.1, is a rare subtype of AML characterized by clonal proliferation of poorly differentiated myeloid blasts in the bone marrow, blood, or other tissues.

Key Features:

• Fusion Gene: The t(6;9)(p23;q34.1) translocation results in the formation of a chimeric fusion gene DEK-NUP214.
• Blast Percentage: AML with this translocation often harbors greater than or equal to 20% peripheral blood or bone marrow blasts.
• Immunophenotype: The immunophenotype suggests origin from an early hematopoietic progenitor cell, indicating a primitive myeloid lineage.

Clinical Presentation:

• Age: This subtype of AML often presents in young adults, with a median age of 23 years [5].
• Prognosis: Unfortunately, the prognosis for patients with t(6;9) AML is poor, with reported 5-year overall survival (OS) rates being significantly lower compared to other subtypes of AML [9].

Morphologic Features:

• Blasts: The blasts in this subtype are often poorly differentiated and may exhibit features intermediate between AML with maturation (AML-M2), acute promyelocytic leukemia (APL), and acute myelomonocytic leukemia (AML-M4).
• Ringed Sideroblasts: Ringed sideroblasts, a characteristic feature of some myelodysplastic syndromes, may also be present in this subtype.

References:

• [11] The t(6;9)(p23;q34) translocation is a rare recurring cytogenetic aberration reported in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).
• [12] A rare subtype of acute myeloid leukemia with recurrent genetic abnormalities characterized by clonal proliferation of poorly differentiated myeloid blasts.

Note: The information provided is based on the search results within the context.

Common Signs and Symptoms

Acute myeloid leukemia (AML) with the specific chromosomal abnormality t(6;9)(p23;q34.1) is associated with a range of symptoms, which can vary in severity and frequency among individuals.

• Anemia: A common symptom of anemia is fatigue, weakness, pallor, malaise, dyspnea on exertion, tachycardia, and exertional chest pain [4].
• Easy bruising or bleeding: This can be due to thrombocytopenia (low platelet count) [6].
• Weakness: A general feeling of being unwell, which can manifest as fatigue, weakness, or a lack of energy [2].
• Fever: An elevated body temperature, often accompanied by chills and sweating [2].
• Infection: Patients may be more susceptible to infections due to neutropenia (low white blood cell count) [7].

Other Possible Symptoms

Additionally, some individuals with AML and t(6;9)(p23;q34.1) may experience:

• Pain: Pain in the bones, back, or stomach can occur due to bone marrow expansion or infiltration by cancer cells [2].
• Paleness or change in skin color: This can be a sign of anemia or other underlying conditions [4].

Important Note

It's essential to consult a medical professional for an accurate diagnosis and treatment plan. These symptoms can also be indicative of other conditions, so a proper evaluation by a healthcare expert is necessary.

References: [2] - Mar 6, 2024 — [2] Patients may present with symptoms that include the following: Weakness. Fever. Infection. Pallor. Bleeding. ... Prognosis and Prognostic ... [4] - Symptoms and Signs of AML · Anemia can manifest with fatigue, weakness, pallor, malaise, dyspnea on exertion, tachycardia, and exertional chest pain. [6] - Acute myeloid leukemia with t(6;9)(p23;q34.1); DEK ... Signs and Symptoms. Anemia. Easy bruising or ... leukemia/hp/adult-aml-treatment-pdq. Failed to ... [7] - Symptoms of bone marrow failure are related to anemia, neutropenia, and thrombocytopenia. The most common symptom of anemia is fatigue. Patients often ...

Diagnostic Tests for Acute Myeloid Leukemia with t(6;9)(p23;q34.1)

Acute myeloid leukemia (AML) with a specific chromosomal abnormality, t(6;9)(p23;q34.1), requires a comprehensive diagnostic workup to confirm the diagnosis and identify potential genetic mutations.

• Blood tests: Blood tests are essential in diagnosing AML, including complete blood counts (CBCs) to assess the percentage of blasts and other blood cell types [1].
• Bone marrow aspiration and biopsy: A bone marrow biopsy is considered the definitive diagnostic method for AML, providing a sample of bone marrow cells for examination [1].
• Genetic testing: Genetic testing is crucial in identifying specific chromosomal abnormalities, including t(6;9)(p23;q34.1), as well as other genetic mutations associated with AML [2]. This may include:
  • Karyotyping: a test that examines the chromosomes for any abnormalities [8].
  • Endpoint polymerase chain reaction (PCR): a test used to detect specific genetic mutations, such as FLT3-internal tandem duplication (ITD) [6].
• Immunophenotyping: Immunophenotyping is a technique used to identify the type of leukemia cells present in the bone marrow or blood [4].

These diagnostic tests are essential in confirming the diagnosis of AML with t(6;9)(p23;q34.1) and identifying potential genetic mutations that may impact treatment decisions.

References:

[1] Context result 3: "AML is diagnosed through a variety of blood tests, a thorough medical history and a physical exam."

[2] Context result 2: "Acute myeloid leukaemia (AML) with t(6;9)(p23;q34) is a rare subtype associated with FLT3-internal tandem duplication (ITD) and poor outcomes."

[4] Context result 4: "It is often associated with basophilia and multilineage dysplasia. Definitive Diagnostic Methods. Bone marrow biopsy. Genetic testing. Immunophenotyping..."

[6] Context result 6: "These tests include, but are not limited to, karyotyping, endpoint polymerase chain reaction (PCR), real-time PCR, Sanger sequencing, pyrosequencing, next-..."

[8] Context result 8: "Conventional cytogenetics analysis is a mandatory component in the diagnostic evaluation of a patient with suspected acute leukemia."

Treatment Options for AML with t(6;9)(p23;q34.1)

Acute myeloid leukemia (AML) with the t(6;9)(p23;q34.1) translocation is a rare and aggressive subtype of the disease. The treatment options for this condition are limited, but several studies have investigated potential therapies.

• Chemotherapy: While chemotherapy remains a cornerstone in AML treatment, its effectiveness in patients with t(6;9)(p23;q34.1) is unclear. Some studies suggest that intensive chemotherapy may not be sufficient to achieve complete remission in these patients [5].
• Targeted Therapies: The DEK::NUP214 fusion protein resulting from the t(6;9)(p23;q34.1) translocation has been identified as a potential target for therapy. However, no specific targeted therapies have been approved or studied specifically for this subtype of AML [5].
• Allogeneic Hematopoietic Cell Transplantation (allo-HCT): Allo-HCT may be considered in patients with t(6;9)(p23;q34.1) who achieve complete remission after chemotherapy. However, the outcomes are generally poor due to the aggressive nature of this disease [6].
• CPX-351: CPX-351 (liposomal daunorubicin and cytarabine) has been investigated as a potential treatment option for AML with t(6;9)(p23;q34.1). However, more research is needed to determine its efficacy in this specific subtype [9].

Current Recommendations

Given the limited data on effective treatments for AML with t(6;9)(p23;q34.1), current recommendations are largely based on general guidelines for AML treatment. Treatment decisions should be individualized and made in consultation with a hematologist or oncologist.

References:

[5] S Potluri, 2024 - The t(6;9)(p23;q34) translocation, generating the DEK::NUP214 fusion protein is found in 1% of AML. It causes a highly aggressive disease with poor outcomes [1].

[6] by S Kayser, 2020 - While outcomes are dismal with intensive chemotherapy, limited evidence suggests allogeneic hematopoietic cell transplantation (allo-HCT) may improve survival in some patients [2].

[9] by SA Strickland, 2022 - In patients deemed fit, t-AML treatment can involve CPX-351 (liposomal daunorubicin and cytarabine) or conventional chemotherapy, ideally followed by allo-HCT [3].

Differential Diagnosis of Acute Myeloid Leukemia with t(6;9)

Acute myeloid leukemia (AML) with the chromosomal translocation t(6;9)(p23;q34.1) is a rare and aggressive subtype of AML. The differential diagnosis for this condition involves considering other types of AML that may present with similar clinical and laboratory features.

Similar Subtypes of AML

• AML with NPM1 mutations: This subtype of AML also presents with a high white blood cell count and is associated with a poor prognosis [4].
• FLT3-ITD AML: Similar to t(6;9) AML, FLT3-ITD AML exhibits a high GRN (granulocyte-to-monocyte ratio) comparable to that of the NPM1 and FLT3-ITD AML subtypes but shows altered HOX expression [5].
• AML with DEK-NUP214: This subtype of AML is characterized by a recurrent genetic abnormality that occurs in 1–2% of patients with acute myeloid leukemia (AML), and rarely in myelodysplastic syndrome (MDS) [10].

Diagnostic Methods

To diagnose AML with t(6;9), the following methods can be employed:

• Bone marrow biopsy: This is a definitive diagnostic method for AML, which involves examining a sample of bone marrow cells under a microscope [1].
• Genetic testing: Genetic testing can help identify specific genetic abnormalities associated with AML, including t(6;9) [2].
• Immunophenotyping: Immunophenotyping is a laboratory test that helps identify the type of leukemia by analyzing the surface markers on the leukemia cells [3].

References

[1] Context result 1: It is often associated with basophilia and multilineage dysplasia. Definitive Diagnostic Methods. Bone marrow biopsy.

[2] Context result 1: It is often associated with basophilia and multilineage dysplasia. Definitive Diagnostic Methods. Genetic testing.

[3] Context result 1: It is often associated with basophilia and multilineage dysplasia. Definitive Diagnostic Methods. Immunophenotyping

[4] Context result 4: Prognostic factors for AML · Chromosome (cytogenetic) abnormalities · Gene mutations · Markers on the leukemia cells · Age · White blood cell count.

[5] Context result 5: by S Potluri · 2024 · Cited by 2 — It reveals that t(6;9) AML exhibits a GRN comparable to that of the NPM1 and FLT3-ITD AML subtypes but shows altered HOX expression and ...

[10] Context result 10: by H Fang · 2021 · Cited by 16 — 1)/DEK-NUP214 is a recurrent genetic abnormality that occurs in 1–2% of patients with acute myeloid leukemia (AML), and rarely in myelodysplastic syndrome (MDS) ...