B-lymphoblastic leukemia/lymphoma with BCR-ABL1

Definition and Characteristics

B-lymphoblastic leukemia/lymphoma (B-ALL/LBL) with BCR-ABL1 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.

• This condition lacks the BCR-ABL1 translocation, which is a genetic abnormality typically found in chronic myeloid leukemia (CML) [1].
• The disease originates from B-lymphoblasts and involves a translocation between the BCR gene on chromosome 22 and another gene, but not ABL1 [6].

Gene Expression Profile

The gene expression profile of B-ALL/LBL with BCR-ABL1-like is similar to that of B-ALL with t(9;22)(q34.1;q11.2) BCR-ABL1, but lacks the BCR-ABL1 fusion gene [7].

Prevalence and Prognosis

• In childhood B-ALLs, Ph-like B-ALL comprises 10% of NCI standard-risk cases and 15% of high-risk cases [3].
• Recent studies have shown promising results with improvement in outcomes for BCR-ABL1–like B-ALL with the addition of a tyrosine kinase inhibitor [9].

References

[1] Definition of B-lymphoblastic leukemia/lymphoma (B-ALL/LBL) without BCR-ABL1 translocation. [2] BCR-ABL1-like B-lymphoblastic leukemia/lymphoma (BCR-ABL1-like ALL or Ph-like ALL). [3] Prevalence of Ph-like B-ALL in childhood B-ALLs. [6] Definition, A B-lymphoblastic leukemia/lymphoma that derives from B-lymphoblasts and carries a translocation between the BCR gene on chromosome 22 and another gene, but not ABL1. [7] Gene expression profile of B-ALL/LBL with BCR-ABL1-like. [8] Adult B-lymphoblastic leukemia/lymphoma, BCR-ABL1-like abnormality shared between cytogenetic findings at diagnosis of B-ALL and t-MN.

Common Signs and Symptoms

B-lymphoblastic leukemia/lymphoma (B-ALL) with BCR-ABL1-like features can present with a range of symptoms, which may vary in severity among individuals. The following are some common signs and symptoms associated with this condition:

• Anemia: A decrease in the number of red blood cells, leading to fatigue, weakness, and shortness of breath [10].
• Arthralgias: Joint pain or discomfort [1].
• Bone pain: Pain or tenderness in the bones, particularly in the back, hips, or ribs [1, 2].
• Elevated white blood cell count: An increase in the number of white blood cells, which can indicate an infection or leukemia [2].
• Easy bruising or bleeding: Easy bruising or bleeding due to a decrease in platelets or clotting factors [14].
• Fatigue: Feeling tired or weak, even after rest [3, 13].
• Fever: A high temperature, which can be a sign of infection or leukemia [4, 14].
• Pain or fullness below the ribs on the left side: Pain or discomfort in the upper abdomen, which can indicate liver or spleen involvement [5].
• Painless lumps in the armpits, groin, neck, or belly: Swollen lymph nodes, which can be a sign of leukemia or lymphoma [4].

Other Possible Symptoms

In addition to these common symptoms, some individuals with B-ALL/B-LBL may experience:

• CNS symptoms: Headaches, confusion, or other neurological problems due to leukemia cells in the central nervous system [3].
• Dyspnea: Shortness of breath or difficulty breathing [14].
• Infection: Increased susceptibility to infections due to a weakened immune system [11].
• Night sweats: Hot flashes or night sweats, which can be a sign of infection or leukemia [4].

It's essential to note that the severity and presentation of symptoms can vary among individuals, and not everyone with B-ALL/B-LBL will experience all of these symptoms. If you suspect you or someone else may have this condition, it's crucial to consult a healthcare professional for proper diagnosis and treatment.

References:

[1] - Context result 1 [2] - Context result 2 [3] - Context result 3 [4] - Context result 4 [10] - Context result 10 [14] - Context result 14

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

The diagnosis of B-lymphoblastic leukemia/lymphoma (B-ALL) associated with the BCR-ABL1 genetic abnormality can be challenging due to its high rate of relapse and poor clinical outcomes [2]. To confirm this type of cancer, diagnostic tests are essential.

Methods for Detection

Several methods can detect BCR-ABL1 in patients with B-ALL:

• BCR/ABL1, p210, mRNA Detection: This method uses Reverse Transcription-PCR (RT-PCR) to monitor most patients with chronic myeloid leukemia (CML) [3].
• Immunophenotyping and Genetics: Positive genetics and/or immunophenotyping can confirm the diagnosis of BCR-ABL1-like B-ALL [4].
• Bone Marrow Examination: A bone marrow examination is necessary to detect recurrent common chromosome abnormalities associated with B-cell acute lymphoblastic leukemia/lymphoma (B-ALL/LBL) [5].

Qualitative Screening Tests

A qualitative screening test can be used for the initial diagnosis of chronic myeloid leukemia (CML) or acute lymphoblastic leukemia/lymphoma (ALL), including those with BCR-ABL1 [7].

Laboratory Methodologies

Recent studies have reviewed laboratory methodologies for routine detection of BCR-ABL1-like ALL, providing a brief overview of the genetic profile and clinical features [8].

In summary, diagnostic tests such as BCR/ABL1, p210, mRNA Detection, immunophenotyping, genetics, bone marrow examination, and qualitative screening tests can help detect BCR-ABL1 in patients with B-lymphoblastic leukemia/lymphoma.

References:

[1] Not provided [2] 2. by BJ Siegele · 2018 · Cited by 41 — [3] 3. Monitoring of most patients with chronic myeloid leukemia should be performed using BCRAB / BCR/ABL1, p210, mRNA Detection, Reverse Transcription-PCR (RT-PCR), ... [4] 4. Diagnostic Confirmation. This histology can only be determined by positive genetics and/or immunophenotyping, diagnostic confirmation will always be 3. Grade. [5] 5. Detecting, at diagnosis, recurrent common chromosome abnormalities associated with B-cell acute lymphoblastic leukemia/lymphoma (B-ALL/LBL) and Philadelphia ... [7] 7. This qualitative screening test is appropriate for initial diagnosis of chronic myeloid leukemia (CML) or acute lymphoblastic leukemia/lymphoma (ALL). [8] 8. by JL Conant · 2019 · Cited by 14 —

Treatment Options for B-ALL with BCR-ABL1

B-lymphoblastic leukemia/lymphoma (B-ALL) with BCR-ABL1 is a type of blood cancer that requires targeted therapy. The treatment options for this condition are evolving, and several drugs have shown great efficacy in managing the disease.

CD19-directed therapies and tyrosine kinase inhibition

• CD19-directed therapies, such as blinatumomab, have been shown to be effective in treating B-ALL with detectable minimal residual disease (MRD) [1].
• Tyrosine kinase inhibitors (TKIs), targeting BCR::ABL1+ blasts, also demonstrate great efficacy in B-ALL treatment [1].

Combination therapy

• Combination therapy using blinatumomab and/or inotuzumab ozogamycin may be considered for patients with B-ALL and detectable MRD [2].
• The addition of tyrosine kinase inhibitors (TKIs) to the treatment regimen may benefit patients with ABL-class rearrangements [3].

Other treatment options

• Chemotherapy, radiation therapy, stem cell transplant, and/or targeted therapy are other treatment options for acute lymphoblastic leukemia (ALL), including B-ALL [5].
• JAK inhibitors, such as momelotinib and ruxolitinib, have been shown to be effective in reducing the viability of JAK2-positive cells, which may be relevant in treating B-ALL [6].

Current research

• A study is evaluating a drug called ABL001 taken in combination with dasatinib (Sprycel) and prednisone as a possible treatment for B-ALL [4].
• Accurate and timely identification of patients with BCR-ABL1-like B-ALL is critical to determine the most effective treatment, including targeted therapy or combination therapy [8].

References

[1] CD19-directed therapies and tyrosine kinase inhibition targeting BCR::ABL1+ blasts show great efficacy in B-ALL. [2] Patients with B-ALL and detectable MRD should be treated with blinatumomab. In the future, the use of blinatumomab and/or inotuzumab ozogamycin may be considered. [3] According to several studies, patients with ABL-class rearrangements may benefit from the addition of tyrosine kinase inhibitor (TKI) – dasatinib. [4] This research study is evaluating a drug called ABL001 taken in combination with dasatinib and prednisone as a possible treatment for B-ALL. [5] Acute lymphoblastic leukemia (ALL) treatment options include chemotherapy, radiation therapy, stem cell transplant, and/or targeted therapy. [6] Steeghs et al58 recently demonstrated that the JAK inhibitors momelotinib and ruxolitinib indeed are effective in reducing the viability of JAK2-positive cells. [7] BCR-ABL1 is a neoplasm of lymphoblasts committed to the B-cell lineage in which the blasts harbor a translocation between BCR on chromosome 22 and the ABL1 gene. [8] Accurate and timely identification of these patients is critical to determine the treatment, including targeted therapy or combination therapy.

Differential Diagnosis of B-Lymphoblastic Leukemia/Lymphoma (B-LBL) with BCR-ABL1

The differential diagnosis of B-LBL with BCR-ABL1 involves excluding other entities that may present similarly. According to search results, the diagnosis should only be rendered after the exclusion of all other entities, such as B lymphoblastic leukemia/lymphoma, NOS [2].

Entities to Exclude:

• B Lymphoblastic Leukemia/Lymphoma (B-LBL): This entity is characterized by the presence of immature B lineage cells. The diagnosis of B-LBL has mostly depended on the characteristics of B-lymphoblast leukemia/lymphoma by IHC and a complete range of immunophenotypic markers [3, 9].
• Chronic Myeloid Leukemia (CML): CML is a myeloproliferative disorder that can present with a BCR-ABL1 fusion. The presence of the gene sequence known as BCR-ABL1 confirms the diagnosis of CML and a form of acute lymphoblastic lymphoma (ALL), specifically B-LBL [6].
• Malignant Lymphoma: Malignant lymphoma, including B-LBL, can present with similar clinical features. A cytogenetic FISH study that is Negative for a BCR/ABL1 translocation may help to rule out CML and confirm the diagnosis of B-LBL [4].

Key Points:

• The differential diagnosis of B-LBL with BCR-ABL1 requires exclusion of other entities.
• B-LBL is characterized by immature B lineage cells.
• CML can present with a BCR-ABL1 fusion, which may be confused with B-LBL.
• A cytogenetic FISH study that is Negative for a BCR/ABL1 translocation may help to rule out CML and confirm the diagnosis of B-LBL.

References:

[1] by Z Chen · 2020 · Cited by 19 — Chronic myeloid leukemia presenting in lymphoblastic crisis, a differential diagnosis with Philadelphia-positive B-lymphoblastic leukemia. [2] Sep 29, 2023 — Differential diagnosis. B lymphoblastic leukemia / lymphoma, NOS: diagnosis should only be rendered after the exclusion of all other entities ... [3] by X Li · 2021 · Cited by 2 — The diagnosis of B-LBL has mostly depended on the characteristics of B-lymphoblast leukemia/lymphoma by IHC and a complete range of ... [4] Final Diagnosis MALIGNANT LYMPHOMA, B-LYMPHOBLASTIC LEUKEMIA/LYMPHOMA TYPE Cytogenetic FISH studies: Negative for a BCR/ABL1 translocation. [5] by JC Kim · 2023 · Cited by 25 — The BCR-ABL1 fusion drives two hematopoietic malignancies—chronic myelogenous leukemia (CML), a myeloproliferative disorder, and BCR-ABL1 ... [6] Nov 6, 2020 — The presence of the gene sequence known as BCR-ABL1 confirms the diagnosis of CML and a form of acute lymphoblastic lymphoma (ALL), specifically ... [7] by S Loghavi · 2015 · Cited by 98 — The diagnosis is established by immunophenotyping, commonly by flow cytometry (FC), which shows immature B lineage. Many cases