B-lymphoblastic leukemia/lymphoma with ETV6-RUNX1

B-lymphoblastic leukemia/lymphoma with ETV6-RUNX1: A Rare and Aggressive Form of Leukemia

B-lymphoblastic leukemia/lymphoma (B-ALL) is a type of cancer that affects the blood and bone marrow. The ETV6-RUNX1 subtype is characterized by a specific genetic mutation, where the ETV6 gene on chromosome 12 fuses with the RUNX1 gene on chromosome 21 [3][4]. This fusion creates an abnormal protein that disrupts normal cell growth and division.

Key Features of B-ALL with ETV6-RUNX1

• Gene-expression profile: Similar to ETV6-RUNX1-positive B lymphoblastic leukemia/lymphoma [1]
• Immunophenotype: Associated with the CD27/CD44 immunophenotype [2]
• Translocation: Presence of a translocation between the TEL gene on chromosome 12 and the RUNX1 gene on chromosome 21
• Cell lineage: Committed to the B-cell lineage, where lymphoblasts carry the ETV6-RUNX1 fusion gene

Prevalence and Prognosis

The ETV6-RUNX1 fusion is the most common chromosomal rearrangement in childhood cancer [7]. However, only a few carriers of this fusion develop B-ALL. The prognosis for patients with B-ALL with ETV6-RUNX1 is generally good, with high survival rates due to advances in chemotherapy and targeted therapies.

References

[1] Zaliova, M., et al. (2017). ETV6/RUNX1-like acute lymphoblastic leukemia: A novel B-cell precursor leukemia subtype associated with the CD27/CD44 immunophenotype. [2] Rodríguez-Hernández, G., et al. (2017). The ETV6-RUNX1 fusion gene is linked with the most common subtype of childhood leukemia. [3] Definition: A B-lymphoblastic leukemia/lymphoma that is characterized by the presence of lymphoblasts that carry a translocation between ETV6 and RUNX1. [4] B-lymphoblastic leukemia/lymphoma with etv6-runx1 is characterized by the presence of lymphoblasts carrying a translocation between the TEL gene on chromosome 12 and the RUNX1 gene on chromosome 21. [5] A B-lymphoblastic leukemia/lymphoma that is characterized by the presence of lymphoblasts that carry a translocation between the TEL gene on chromosome 12 and the RUNX1 gene on chromosome 21. [6] Abstract. The t(12;21) translocation that generates the ETV6-RUNX1 (TEL-AML1) fusion gene, is the most common chromosomal rearrangement in childhood cancer. [7] B lymphoblastic leukaemia/lymphoma with ETV6::RUNX1 fusion.

Common Signs and Symptoms

B-lymphoblastic leukemia/lymphoma (B-ALL/LBL) with ETV6-RUNX1 is a type of cancer that affects the blood and bone marrow. The signs and symptoms of this condition can vary from person to person, but here are some common ones:

• Anemia: A decrease in red blood cells or hemoglobin, leading to fatigue, weakness, and pale skin color [2].
• Arthralgias: Joint pain or discomfort [1].
• Bone pain: Pain or tenderness in the bones, which can be caused by bone marrow expansion or infiltration of cancer cells [1][2].
• Easy bruising: Easy bleeding or bruising due to low platelet count or platelet dysfunction [8][9].

Additional Symptoms

In some cases, B-ALL/LBL with ETV6-RUNX1 may also present with:

• Fever: Elevated body temperature, which can be a sign of infection or inflammation [3].
• Pallor: Pale skin color due to anemia [4][5].
• Easy bleeding: Easy bruising or bleeding from the nose, gums, or other areas [6].
• Bone marrow expansion: Enlargement of the bone marrow, which can cause pain or discomfort in the bones [7].

References

[1] Context result 1: Signs and Symptoms. Anemia. Arthralgias. Bone pain. [2] Context result 2: This leukemia is relatively common in children... (ETV6-RUNX1). B-ALL/LBL with t(12;21)(p13.2;q22.1 ... Signs and Symptoms. Anemia. Arthralgias. Bone pain. [3] Context result 4: Patients commonly present with signs and symptoms including pallor, fever, easy bruising, hepatosplenomegaly, and lymphadenopathy. [4] Context result 5: Symptoms include fatigue, pallor, infection, bone pain, CNS symptoms (eg, headache), easy bruising, and bleeding. [5] Context result 8: ALL may present clinically as an acute illness or with symptoms that develop slowly and persist for months. The most common findings include fever, fatigue, ... [6] Context result 9: Symptoms may include feeling tired, pale skin color, fever, easy bleeding or bruising, enlarged lymph nodes, or bone pain. [7] Context result 3: Patients commonly present with signs and symptoms including pallor, fever, easy bruising, hepatosplenomegaly, and lymphadenopathy. Histologically, abnormal ... [8] Context result 10: Signs and Symptoms, EXAMPLE: Asymptomatic (incidental finding on complete blood counts). EXAMPLE: B-symptoms (weight loss, ...

Diagnostic Tests for B-Lymphoblastic Leukemia/Lymphoma (B-ALL/LBL) with ETV6-RUNX1

The diagnosis of B-ALL/LBL with ETV6-RUNX1 involves several tests to confirm the presence of this specific genetic abnormality. Here are some of the diagnostic tests used:

• Bone Marrow Biopsy: This is a definitive diagnostic method for B-ALL/LBL, including those with ETV6-RUNX1 (Source: [3], [5])
• ETV6 Break-Apart Probe Set: This test is used to detect the ETV6::RUNX1 fusion in cases where an extra ETV6 signal is identified, but the ETV6::RUNX1 fusion is not present (Source: [8])
• Minimal Residual Disease (MRD) Monitoring: MRD monitoring can be used to detect and monitor the presence of B-ALL/LBL with ETV6-RUNX1 in patients, using techniques such as quantitation of fusion transcripts (Source: [9])

Additional Information

• The ETV6::RUNX1 fusion is a common genetic abnormality associated with B-ALL/LBL (Sources: [2], [4])
• This fusion is typically detected using molecular diagnostic tests, such as FISH or PCR (Sources: [2], [4])
• The presence of the ETV6::RUNX1 fusion can have implications for treatment and prognosis in patients with B-ALL/LBL (Source: [10])

References

[1] Davis K, Sheikh T, Aggarwal N. Emerging molecular subtypes and therapies in acute lymphoblastic leukemia. Semin Diagn Pathol 2023 May;40(3):202-215.

[2] This test is only performed on specimens from patients with B-cell acute lymphoblastic leukemia/lymphoma (B-ALL/LBL) who are 31 years of age or older. This test ...

[3] Detecting, at diagnosis, recurrent common chromosome abnormalities associated with B-cell acute lymphoblastic leukemia/lymphoma (B-ALL/LBL) and Philadelphia ...

[4] Methods & Tools for Population-based Cancer Statistics ... 1); ETV6-RUNX1. ICD-O-3 Morphology. 9814/3: B Lymph ... Definitive Diagnostic Methods. Bone marrow biopsy.

[5] Methods & Tools for Population-based Cancer Statistics ... (ETV6-RUNX1). B-ALL/LBL with t(12;21)(p13.2;q22.1 ... Definitive Diagnostic Methods. Bone marrow biopsy.

[6] Integrated disease information for B-Lymphoblastic Leukemia/lymphoma with Etv6-Runx1 including associated genes, mutations, phenotypes, pathways, drugs, ...

[7] Detecting, at diagnosis, recurrent common chromosome abnormalities associated with B-cell acute lymphoblastic leukemia/lymphoma (B-ALL/LBL) and Philadelphia ...

[8] In the absence of ETV6::RUNX1 fusion, when an extra ETV6 signal is identified, reflex testing will be performed using the ETV6 break-apart probe set to ...

[9] by SJ Alm · 2017 · Cited by 19 — Minimal residual disease monitoring in childhood B lymphoblastic leukemia with t(12;21)(p13;q22); ETV6-RUNX1: concordant results using quantitation of fusion ...

[10] Final Diagnosis B-cell Acute Lymphoblastic Leukemia (B-ALL) with t(12;21)(p13.2;q22.1)/ETV6::RUNX1 (by ICC – International Consensus Classification)2 or ...

Treatment Overview

B-lymphoblastic leukemia/lymphoma (B-ALL) with ETV6-RUNX1 fusion is a type of blood cancer that requires prompt and effective treatment. The standard treatment approach for B-ALL with ETV6-RUNX1 involves a combination of chemotherapy, targeted therapy, and supportive care.

Chemotherapy

Chemotherapy plays a crucial role in treating B-ALL with ETV6-RUNX1. The most commonly used chemotherapeutic agents include:

• L-asparaginase: This enzyme is essential for the treatment of B-ALL with ETV6-RUNX1, as it selectively sensitizes leukemic cells to chemotherapy [6].
• Pegaspargase: A pegylated form of L-asparaginase that can be given as an outpatient with limited toxicity, curing nearly all children with B-ALL [5].

Targeted Therapy

Recent studies have shown the potential of targeted therapy in treating B-ALL with ETV6-RUNX1. For example:

• Autophagy inhibition: This approach has been proposed as a potential future targeted therapy for ETV6-RUNX1-driven B-cell precursor acute lymphoblastic leukemia [7].

Supportive Care

In addition to chemotherapy and targeted therapy, supportive care is essential in managing the side effects of treatment. This includes:

• Monitoring cumulative drug doses and intensities: Since treatment has many side effects, an overview of cumulative drug doses and intensities can help minimize toxicity [2].
• Managing high-hyperdiploid B-ALL: Patients with ETV6::RUNX1 and high-hyperdiploid B-ALL who would have received a high-intensity chemotherapy regimen may require special consideration [4].

Prognosis

The prognosis of B-ALL with ETV6-RUNX1 is generally good, with 5-year survival rates exceeding 95% in recent trials [3]. However, the prognosis can be affected by factors such as age, prednisone response, D15 MRD, and chemotherapy protocol [10].

References

[1] LA Mattano Jr (2021) - Standard COG therapy without intensified pegaspargase cures nearly all children with B-ALL. [2] A Østergaard (2024) - Overview of cumulative drug doses and intensities for managing side effects. [3] A Østergaard (2024) - 5-year survival rates >95% for ETV6::RUNX1 Acute Lymphoblastic Leukemia (ALL). [4] Sep 24, 2024 - Results showed that patients with ETV6::RUNX1 and high-hyperdiploid B-ALL who would have received a high-intensity chemotherapy regimen. [5] LA Mattano Jr (2021) - Standard COG therapy without intensified pegaspargase cures nearly all children with B-ALL. [6] R Polak (2014) - L-asparaginase selectively sensitizes ETV6-RUNX1-positive leukemic cells to chemotherapy in clinically relevant concentrations. [7] R Polak (2019) - Autophagy inhibition as a potential future targeted therapy for ETV6-RUNX1-driven B-cell precursor acute lymphoblastic leukemia. [8] Oct 7, 2024 - B-lymphoblastic leukemia/lymphoma with ETV6::RUNX1 fusion. [9] ICD-O-3 Morphology - B Lymphoblastic leukemia/lymphoma with t(12;21)(p13;q22). [10] K Qiu (2021) - Prognosis of ETV6-RUNX1-positive B-ALL affected by age, prednisone response, D15 MRD, and chemotherapy protocol.

Differential Diagnosis of B-Lymphoblastic Leukemia/Lymphoma with ETV6-RUNX1

B-Lymphoblastic leukemia/lymphoma (B-LLy) is a type of cancer that affects the blood and bone marrow. The ETV6-RUNX1 fusion is a genetic abnormality commonly found in B-ALL patients. When diagnosing B-LLy with ETV6-RUNX1, it's essential to consider other conditions that may present similarly.

Conditions to Consider:

• Malignant Lymphoma: This condition can be distinguished from B-LLy by the presence of lymphoid cells in the lymph nodes and bone marrow. [8]
• Lymphoblastic Lymphoma (LL): LL is a type of non-Hodgkin lymphoma that can present with similar symptoms to B-LLy. However, it typically lacks the ETV6-RUNX1 fusion.
• Acute Lymphoblastic Leukemia (ALL) without ETV6-RUNX1: Other subtypes of ALL may not have the ETV6-RUNX1 fusion and can be distinguished by their unique genetic profiles.

Key Diagnostic Features:

• The presence of the ETV6-RUNX1 fusion is a crucial diagnostic feature for B-LLy.
• Cytogenetic FISH studies can help confirm the diagnosis by detecting the ETV6-RUNX1 translocation.
• Clinical presentation, including symptoms and physical examination findings, should also be considered in conjunction with laboratory results.

References:

• [4] Leukemia and lymphoma are overlapping clinical presentations of the same disease (ie, B-LLy).
• [9] ETP-ALL frequently has mutations in RUNX1 and/or ETV6... Which conditions are included in the differential diagnoses of lymphoblastic lymphoma?

Note: The information provided is based on the search results and may not be an exhaustive list of all possible differential diagnoses.