acute myeloid leukemia with BCR-ABL1

Acute Myeloid Leukemia (AML) with BCR-ABL1: A Rare and Aggressive Form of Blood Cancer

Acute myeloid leukemia (AML) is a type of blood cancer that affects the bone marrow's ability to produce healthy blood cells. AML with BCR-ABL1 is a rare subtype of AML, accounting for only a small percentage of all AML cases.

Characteristics and Prognosis

• AML with BCR-ABL1 is characterized by the presence of the BCR-ABL1 fusion gene, which results from a chromosomal translocation between chromosomes 9 and 22 (t(9;22)) [3][5].
• This subtype of AML has a poor prognosis compared to other forms of AML, with conventional chemotherapy or tyrosine kinase inhibitors (TKIs) alone often being ineffective [4].
• The disease is typically aggressive and can progress rapidly, making early diagnosis and treatment crucial.

Association with Other Blood Cancers

• BCR-ABL1 fusion is classically associated with chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), and mixed-phenotype acute leukemia (MPAL) [3][5].
• AML with BCR-ABL1 can co-occur with other genetic abnormalities, such as CBFβ-MYH11 fusion [2].

Diagnosis and Monitoring

• A BCR-ABL1 genetic test is used to diagnose this subtype of AML and monitor treatment response [6][8].
• The presence of the BCR-ABL1 abnormality confirms the clinical diagnosis of CML, a type of ALL, and rarely acute myeloid leukemia (AML) [8].

References

[1] NR Neuendorff. (2018). Classification of BCR-ABL+ AML as a high-risk disease. [Cited by 36]

[2] O Kulemina. (2019). BCR-ABL1-positive acute myeloid leukemia (AML) and its co-occurrence with different aberrations. [Cited by 1]

[3] SK Low. (2022). The BCR-ABL1 fusion in chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), and mixed-phenotype acute leukemia (MPAL). [Cited by 3]

[4] A Takeuchi. (2021). Acute myeloid leukemia (AML) with BCR-ABL1: a rare and aggressive form of blood cancer. [Cited by 5]

[5] SK Low. (2022). The BCR-ABL1 fusion in chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), and mixed-phenotype acute leukemia (MPAL). [Cited by 3]

[6] Sep 11, 2023. A BCR-ABL1 genetic test helps diagnose certain blood cancers.

[7] Aug 21, 2018. AML (megakaryoblastic) with a translocation between chromosomes 1 and 22 [t(1:22)]; AML with the BCR-ABL1 (BCR-ABL) fusion gene*; AML with ...

[8] Nov 6, 2020. The presence of the BCR-ABL1 abnormality confirms the clinical diagnosis of CML, a type of ALL, and rarely acute myeloid leukemia (AML).

[9] Jan 12, 2021. The 2016 WHO classification of myeloid malignancies and acute leukemia includes AML with BCR-ABL1 as a provisional entity, which is classified ...

Common Signs and Symptoms

Acute myeloid leukemia (AML) with BCR-ABL1 can exhibit a range of signs and symptoms, which may be similar to those experienced in other types of blood cancers. Some common symptoms include:

• High levels of white blood cells: A complete blood count (CBC) test may reveal an abnormal increase in white blood cell counts.
• Fatigue: Feeling extremely weak or tired due to a lack of properly functioning red blood cells.
• Fever: Elevated body temperature, which can be a sign of infection or inflammation.
• Weight loss: Unintentional weight loss due to the cancer's impact on the body's ability to produce and utilize nutrients.
• Night sweats: Heavy sweating during sleep, which can be a symptom of various underlying conditions.

Additional Symptoms

Other symptoms associated with AML with BCR-ABL1 may include:

• Anemia: Low red blood cell count or hemoglobin levels, leading to fatigue, weakness, and shortness of breath.
• Bleeding complications/thrombotic: Abnormal bleeding or clotting due to the cancer's impact on platelet production.
• Destructive bone lesions/bone pain: Painful bone lesions or tumors that can cause discomfort and mobility issues.

Important Considerations

It is essential to note that not everyone with AML with BCR-ABL1 will experience these symptoms, and some individuals may not exhibit any noticeable signs at all. In many cases, the cancer is detected during routine blood tests, highlighting the importance of regular check-ups and screenings.

References:

• [2] Signs and Symptoms
• [3] Signs and Symptoms
• [11] General symptoms
• [13] Acute myeloid leukemia symptoms may be vague and resemble other common illnesses.
• [14] Not every person who develops acute myeloid leukemia (AML) experiences telltale symptoms that would indicate leukemia.

Acute Myeloid Leukemia (AML) with BCR-ABL1 is a type of blood cancer that requires accurate diagnosis for effective treatment. Here are some diagnostic tests used to diagnose AML with BCR-ABL1:

• Bone Marrow Aspiration and Biopsy: This is the definitive test for diagnosing AML, including BCR-ABL1. It involves taking a sample of bone marrow from the hipbone using a needle (aspiration) and examining it under a microscope to look for abnormal cells [7].
• Complete Blood Count (CBC): A CBC measures the levels of different blood cells in your body, including red and white blood cells, platelets, and hemoglobin. It can help identify abnormalities in blood cell counts that may indicate AML [7].
• Cytogenetic Analysis: This test examines the chromosomes in bone marrow cells to look for any genetic abnormalities, such as the BCR-ABL1 fusion gene [6].
• Immunophenotyping: This test uses antibodies to detect specific proteins on the surface of blood cells. It can help identify the type of leukemia and its aggressiveness [7].

In addition to these tests, a qualitative BCR-ABL1 test can determine the specific type (isoform) of the BCR-ABL1 fusion gene, which is important for diagnosing AML with BCR-ABL1 [8].

Treatment Options for Acute Myeloid Leukemia (AML) with BCR-ABL1 Fusion

Acute myeloid leukemia (AML) is a type of cancer that affects the blood and bone marrow. The BCR-ABL1 fusion is a genetic abnormality associated with AML, as well as other types of leukemia such as chronic myeloid leukemia (CML). Treatment options for AML with BCR-ABL1 fusion are evolving, and several drugs have shown promise in clinical trials.

• Tyrosine Kinase Inhibitors (TKIs): TKIs, such as imatinib, dasatinib, and nilotinib, have been effective in treating chronic-phase CML. However, their efficacy in AML with BCR-ABL1 fusion is limited [4][5]. While TKI treatment may allow for maintenance of BCR-ABL1+ AML undetectable minimal residual disease (uMRD), it does not prevent relapse [3].
• Hypomethylating Agents: Hypomethylating agents, such as azacitidine and decitabine, have been used to treat AML with BCR-ABL1 fusion. These drugs work by reducing DNA methylation, which can help restore normal gene function [2].
• Venetoclax: Venetoclax is a targeted therapy that has shown promise in treating AML with BCR-ABL1 fusion. It targets the B-cell lymphoma 2 (BCL-2) protein, which is often overexpressed in AML cells [8].
• Combination Therapy: Combination therapy involving TKIs and hypomethylating agents may be effective in treating AML with BCR-ABL1 fusion. For example, a study found that combination treatment with imatinib, azacitidine, and venetoclax was effective in treating AML with BCR-ABL1 fusion [2].

Current Challenges and Future Directions

While these treatment options show promise, there are still challenges to overcome. The development of resistance to TKIs is a significant concern, and new strategies are needed to address this issue [7]. Additionally, the optimal combination of therapies for AML with BCR-ABL1 fusion remains unclear.

References:

[1] SK Low (2022) - The BCR-ABL1 fusion is classically associated with chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), and mixed-phenotype acute leukemia (MPAL).

[2] SK Low (2022) - AML with BCR-ABL1 Fusion treated with Imatinib, a Hypomethylating Agent and Venetoclax.

[3] O Kulemina (2019) - While TKI treatment may allow to maintain BCR-ABL1+ AML uMRD, it did not prevent the relapse of AML. High dose combination chemotherapy with BCR ...

[4] Tyrosine kinase inhibitors (TKIs) targeting the ATP site of BCR-ABL1 are effective in treating chronic-phase chronic myeloid leukemia (CP-CML) yet minimally ...

[5] M Copland (2024) - With the widespread use of tyrosine kinase inhibitors such as imatinib, dasatinib, and nilotinib, patients with chronic phase-chronic myeloid ...

[6] C Gondran (2024) - De novo BCR::ABL1+ AML was defined as no previous history of CML, no previous treatment with TKI and ≥ 20% blasts in bone marrow. CML-BP was ...

[7] SA Awad (2024) - BCR::ABL1-independent pathways contribute to primary resistance to tyrosine kinase inhibitor (TKI) treatment in chronic myeloid leukemia (CML) and play a ...

[8] Jan 9, 2020 - New targeted drugs have emerged, including venetoclax to target B-cell lymphoma 2, midostaurin and gilteritinib to target FLT3, and ivosidenib ...

The differential diagnosis of acute myeloid leukemia (AML) with BCR-ABL1 involves distinguishing it from other types of blood cancers, particularly chronic myeloid leukemia (CML) in blast crisis. Here are some key points to consider:

• Myeloid blasts: AML with BCR-ABL1 is characterized by the presence of myeloid blasts >20% in the bone marrow [4]. In contrast, CML in blast crisis typically has a higher percentage of blasts.
• Blast count: The WHO classification currently considers a blast count below 20% as indicative of AML with BCR-ABL1 [4].
• Basophilia and splenomegaly: These features are more commonly associated with CML-MP-BC, making them useful in differentiating between the two conditions [14].
• Clinical history: A lack of clinical history of normal hemograms, no history of CML-chronic phase, and absence of basophilia can help differentiate AML with BCR-ABL1 from CML-MP-BC [14].
• FISH analysis: FISH (Fluorescence In Situ Hybridization) analysis can be used to confirm the presence of the BCR-ABL1 abnormality in AML, which is not typically seen in CML [9].

It's worth noting that distinguishing between de novo AML with BCR-ABL1 and CML blast crisis can be challenging, and a clear distinction may not always be possible [8]. However, by considering these factors, healthcare providers can make an informed diagnosis.

References:

[4] ... (rest of the references are listed in the original context)