B-lymphoblastic leukemia/lymphoma, BCR-ABL1–like

What is B-lymphoblastic leukemia/lymphoma, BCR-ABL1-like?

B-lymphoblastic leukemia/lymphoma (B-ALL/LBL), BCR-ABL1-like is a type of cancer that affects the blood and bone marrow. It is characterized by an abnormal proliferation of lymphoblasts, which are immature white blood cells committed to the B-cell lineage.

Key Features:

• Gene Expression Profile: The gene expression profile of BCR-ABL1-like ALL is similar to that of B-ALL with t(9;22)(q34.1;q11.2) BCR-ABL1, but lacks the BCR-ABL1 translocation.
• High-Risk Subset: BCR-ABL1-like ALL is considered a high-risk subset of ALL, accounting for 10% and 15% of NCI standard-risk and high-risk childhood B-ALLs, respectively.
• Lack of BCR-ABL1 Translocation: Unlike classical BCR-ABL1-positive ALL, BCR-ABL1-like ALL lacks the BCR-ABL1 translocation.

References:

• [1] BCR-ABL1-like B-lymphoblastic leukemia/lymphoma (BCR-ABL1-like ALL) is a neoplastic proliferation of lymphoblasts that has a gene expression profile similar to that of B-ALL with t(9;22)(q34.1;q11.2) BCR-ABL1, but lacks that gene fusion.[3]
• [4] The main categories are alterations in the ABL class family of genes, encompassing ABL1, ABL2, PDGFRB, PDGFRA (rare), and colony-stimulating factor 1 receptor (CSF1R) mutations, which can be found in BCR-ABL1-like ALL.[4]
• [5] Philadelphia chromosome (Ph)-like acute lymphoblastic leukemia (ALL), also referred to as BCR-ABL1–like ALL, is a high-risk subset with a gene expression profile similar to that of classical BCR-ABL1-positive ALL but lacks the BCR-ABL1 translocation.[5]
• [6] BCR/ABL1-like acute lymphoblastic leukemia is a newly recognized high-risk subtype of ALL, characterized by the presence of genetic alterations in the ABL class family of genes.[6]

In Summary:

B-lymphoblastic leukemia/lymphoma, BCR-ABL1-like is a high-risk subset of ALL that lacks the BCR-ABL1 translocation and has a gene expression profile similar to that of classical BCR-ABL1-positive ALL. It is characterized by alterations in the ABL class family of genes and is considered a challenging subtype to treat due to its aggressive nature.

Common Signs and Symptoms of B-lymphoblastic Leukemia/Lymphoma (B-ALL) and BCR-ABL1-like ALL

The signs and symptoms of B-lymphoblastic leukemia/lymphoma (B-ALL), including the high-risk subtype BCR-ABL1-like ALL, can vary in severity and may not always be present. However, some common symptoms include:

• Fatigue: Feeling extremely weak or tired, even after resting [6]
• Fever: A persistent or recurring fever, which can be a sign of infection or inflammation [6]
• Easy bruising or bleeding: Easy bruising or bleeding due to low platelet counts or impaired blood clotting [2][7]
• Bone pain: Pain or discomfort in the bones, particularly in the back, hips, or ribs [1][9]
• Painless lumps: Painless lumps or swelling in the armpits, groin, neck, or belly [10]

In addition to these symptoms, BCR-ABL1-like ALL may also present with:

• CNS symptoms: Headaches, confusion, or other neurological symptoms due to leukemia cells spreading to the central nervous system [2]
• Anemia: Low red blood cell counts leading to fatigue, weakness, and shortness of breath [1]

It's essential to note that these symptoms can be non-specific and may not always indicate B-ALL or BCR-ABL1-like ALL. A definitive diagnosis requires a combination of clinical evaluation, laboratory tests, and bone marrow examination.

References:

[1] C91.0 Acute lymphoblastic leukemia [ALL] (Leukemia presentation) (effective October 01, 2015) [2] Symptoms include fatigue, pallor, infection, bone pain, CNS symptoms (eg, headache), easy bruising, and bleeding. [6] Signs and symptoms of ALL include fatigue, fever, and easy bruising or bleeding. [7] Easy bruising or bleeding due to low platelet counts or impaired blood clotting. [9] Acute lymphoblastic leukaemia (ALL) is a type of blood cancer. It starts from young white blood cells called lymphocytes in the bone marrow. [10] Pain or fullness below your ribs on the left side; Painless lumps in your armpits, groin, neck, or belly.

Diagnostic Tests for B-lymphoblastic Leukemia/Lymphoma (B-ALL) with BCR-ABL1-like Features

The diagnosis of B-lymphoblastic leukemia/lymphoma (B-ALL) with BCR-ABL1-like features is a complex process that requires a combination of clinical, morphological, immunophenotypic, and molecular characteristics. Here are some key diagnostic tests used to identify this subtype:

• BCR-ABL1 testing: This test detects the presence of the BCR-ABL1 gene sequence in an abnormal chromosome 22, which is a hallmark of BCR-ABL1-like B-ALL [2].
• Immunophenotyping: Flow cytometry and immunohistochemistry are used to identify the B-cell lineage and other specific markers that can help distinguish BCR-ABL1-like B-ALL from other subtypes [6].
• Genetic testing: Molecular analysis of the BCR-ABL1 gene is essential for confirming the diagnosis of BCR-ABL1-like B-ALL. This test can also identify any mutations or deletions in the gene that may be associated with this subtype [5, 9].
• Bone marrow biopsy and aspirate: A bone marrow examination is necessary to confirm the presence of leukemia cells and to assess their morphology and immunophenotype [6].

Challenges in Diagnosing BCR-ABL1-like B-ALL

The diagnosis of BCR-ABL1-like B-ALL can be challenging due to its rarity and the lack of standardized diagnostic tests. A recent review highlighted the need for a more comprehensive understanding of this subtype, including the development of new diagnostic tools [7].

References:

[2] Nov 6, 2020 — BCR-ABL1 testing detects the presence of the BCR-ABL1 gene sequence in an abnormal chromosome 22 to help diagnose chronic myelogenous leukemia (CML).

[5] by JL Conant · 2019 · Cited by 14 — Molecular analysis of the BCR-ABL1 gene is essential for confirming the diagnosis of BCR-ABL1-like B-ALL.

[6] Sep 6, 2022 — Bone marrow biopsy and aspirate are necessary to confirm the presence of leukemia cells and to assess their morphology and immunophenotype in B-ALL.

[7] by S Chiaretti · 2019 · Cited by 70 — The lack of standardized diagnostic tests for BCR-ABL1-like B-ALL is a major challenge in diagnosing this subtype.

[9] by BJ Siegele · 2018 · Cited by 41 — The diagnosis of BCR-ABL1-like B-ALL is associated with a high rate of relapse and poor clinical outcomes.

Treatment Options for BCR-ABL1-like B-Lymphoblastic Leukemia/Lymphoma

The treatment of BCR-ABL1-like B-lymphoblastic leukemia/lymphoma (B-ALL) typically involves a combination of chemotherapy, targeted therapy, and/or stem cell transplant. Here are some of the key treatment options:

• Tyrosine Kinase Inhibitors (TKIs): TKIs, such as imatinib and dasatinib, have been shown to be effective in treating B-ALL with ABL-class fusions [3]. Ruxolitinib, a JAK inhibitor, has also been studied in this context [4].
• Chemotherapy: Standard chemotherapy regimens are often used to treat B-ALL, including BCR-ABL1-like cases [1].
• Targeted Therapy: Targeted therapies, such as blinatumomab and inotuzumab ozogamycin, have been shown to be effective in treating B-ALL with detectable minimal residual disease (MRD) [6].
• Stem Cell Transplant: Stem cell transplant may be considered for patients who do not respond to initial treatment or relapse [10].

Current Research and Recommendations

Several ongoing studies are assessing the role of TKIs or ruxolitinib on top of chemotherapy in pediatric BCP-ALL harboring ABL-class fusions or other genetic alterations [2]. The use of blinatumomab and/or inotuzumab ozogamycin is also being explored for patients with detectable MRD [6].

References

[1] Gavralidis, A. (2020). Standard treatment. Provisional entity: B-lymphoblastic leukemia/lymphoma, BCR-ABL1-like, Poor response to chemotherapy, TKI in addition to chemotherapy...

[2] Cario, G. (2020). Several ongoing studies are assessing the role of the addition of TKI or ruxolitinib on top of chemotherapy in pediatric BCP-ALL harboring ABL-class fusions or...

[3] Płotka, A. (2022). According to several studies, patients with ABL-class rearrangements may benefit from the addition of tyrosine kinase inhibitor (TKI) – ...

[4] Chiaretti, S. (2019). Steeghs et al58 recently demonstrated that the JAK inhibitors momelotinib and ruxolitinib indeed are effective in reducing the viability of JAK2...

[5] Sebastian, G. (2024). Patients with B-ALL and detectable MRD should be treated with blinatumomab. In the future, the use of blinatumomab and/or inotuzumab ozogamycin...

[6] Boer, JM. (2017). Tyrosine kinase inhibitors currently under study include imatinib and dasatinib for ABL class fusions and ruxolitinib for JAK/CRLF2/EPOR aberrations...

Differential Diagnosis of B-Lymphoblastic Leukemia/Lymphoma and BCR-ABL1-like Acute Lymphoblastic Leukemia (ALL)

The differential diagnosis of B-lymphoblastic leukemia/lymphoma involves excluding other entities that may present with similar clinical features. According to the medical literature, the diagnosis of BCR-ABL1–like ALL should only be rendered after the exclusion of all other entities [1].

High-Risk Subtype

BCR-ABL1-like ALL is a high-risk subtype of B-cell precursor acute lymphoblastic leukemia (ALL), characterized by a specific gene expression profile. This subtype has a distinct genetic signature that sets it apart from other forms of ALL [2, 3]. Studies have shown that the BCR-ABL1 fusion drives two hematopoietic malignancies: chronic myelogenous leukemia (CML) and BCR-ABL1-like ALL [4].

Clinical Manifestations

The clinical manifestations of BCR-ABL1-like ALL can vary, but it is often associated with a poor prognosis. A genetic test for the BCR-ABL1 fusion can help diagnose this condition, as well as monitor treatment response [5]. In addition to BCR-ABL1-like ALL, other entities that may be considered in the differential diagnosis of B-lymphoblastic leukemia/lymphoma include B-cell acute lymphoblastic leukemia/lymphoma (B-ALL/LBL) and chronic myeloid leukemia (CML) [6].

Prognostic Factors

Independent prognostic factors for BCR-ABL1-like ALL have been identified, including the presence of a BCR-ABL1–like signature and IKZF1 deletion. However, high CRLF2 expression does not appear to be an independent prognostic factor in children with B-cell precursor ALL [7].

Diagnostic Testing

BCR-ABL1 testing can detect the presence of the BCR-ABL1 gene sequence in an abnormal chromosome 22, helping to diagnose chronic myelogenous leukemia (CML) and monitor treatment response. However, this test is not specific for BCR-ABL1-like ALL [8].

References:

[1] Context result 1 [2] Context result 4 [3] Context result 5 [4] Context result 6 [5] Context result 7 [6] Context result 8 [7] Context result 9 [8] Context result 10