mixed phenotype acute leukemia with BCR-ABL1

Mixed-phenotype acute leukemia (MPAL) with BCR-ABL1 rearrangement is a rare and aggressive form of leukemia that combines characteristics of both myeloid and lymphoid lineages. This subtype of MPAL is characterized by the presence of blasts with t(9;22)(q34.1;q11.2) and/or BCR-ABL1 rearrangement, which is also known as Philadelphia chromosome-positive (Ph+) MPAL.

Key Features:

• Blasts express antigens of both myeloid and lymphoid lineages
• Presence of t(9;22)(q34.1;q11.2) and/or BCR-ABL1 rearrangement
• Aggressive clinical course with poor prognosis

According to [3], MPAL with t(9;22)(q34.1;q11.2) fulfills the criteria for MPAL and has blasts with t(9;22) and/or BCR-ABL1 rearrangement.

References:

[3] Mixed-phenotype acute leukemia (MPAL) with t(9;22)(q34.1;q11.2) fulfills the criteria for MPAL and has blasts with t(9;22) and/or BCR-ABL1 rearrangement.

Mixed phenotype acute leukemia (MPAL) with BCR-ABL1, also known as Philadelphia chromosome-positive MPAL, is a rare subtype of acute leukemia that combines characteristics of both lymphoid and myeloid leukemias. The signs and symptoms of MPAL with BCR-ABL1 are similar to those of other acute leukemias.

Common Signs and Symptoms:

• Fatigue [1]
• Weight loss [1]
• Loss of appetite [1]
• Pale skin [1]
• Easy bruising or bleeding [1]
• Frequent infections [1]

These symptoms can be non-specific and may also occur in other conditions. A definitive diagnosis of MPAL with BCR-ABL1 requires laboratory tests, including:

Diagnostic Tests:

• Complete Blood Count (CBC) to detect abnormal white blood cell counts
• Bone marrow biopsy to examine the bone marrow cells
• Genetic testing to confirm the presence of the BCR-ABL1 fusion gene

It's essential to note that MPAL with BCR-ABL1 is a rare and aggressive form of leukemia, and early diagnosis and treatment are crucial for improving outcomes.

References:

[1] Mixed phenotype acute leukemia has qualities of both lymphoid and myeloid leukemias. ... The signs and symptoms of MPAL are similar to those of other acute leukemias. (Search result 1) [2] If a patient is BCR-ABL1-negative, age-appropriate ALL therapy followed by SCT after remission is an acceptable strategy. Important areas for further study are: (1) whether the degree of MPO ... (Search result 2) [3] Mixed-phenotype acute leukemia (MPAL) with t(9;22)(q34.1;q11.2) fulfills the criteria for MPAL with BCR-ABL1. (Search result 10)

Mixed-phenotype acute leukemia (MPAL) with BCR-ABL1 is a rare and aggressive form of leukemia that requires prompt and accurate diagnosis. The diagnostic tests for MPAL with BCR-ABL1 are crucial in determining the presence of this disease.

Immunohistochemistry (IHC): IHC is a primary method for blast immunophenotyping in clinical practice, and it can help identify the presence of BCR-ABL1 in MPAL. This test involves using antibodies to detect specific proteins on the surface of cancer cells [5].

Flow Cytometry (FCM): FCM is another essential diagnostic tool for MPAL with BCR-ABL1. It helps determine the immunophenotypic features of blasts, which are critical in diagnosing this disease [4].

Karyotyping and Fluorescence In Situ Hybridization (FISH): Karyotyping can help identify chromosomal abnormalities, including the t(9;22)(q34;q11.2) translocation associated with BCR-ABL1. FISH is a more sensitive test that can detect specific genetic mutations, including BCR-ABL1 [6].

Polymerase Chain Reaction (PCR): PCR is a molecular diagnostic tool that can help detect the presence of BCR-ABL1 in MPAL. This test involves amplifying specific DNA sequences to identify the presence of this gene mutation.

Testing for t(9;22)(q34;q11.2); BCR-ABL1: Testing for this translocation is essential in diagnosing MPAL with BCR-ABL1. This can be done using FISH, PCR, or karyotyping [10].

In summary, the diagnostic tests for mixed-phenotype acute leukemia with BCR-ABL1 include immunohistochemistry, flow cytometry, karyotyping, fluorescence in situ hybridization, polymerase chain reaction, and testing for t(9;22)(q34;q11.2); BCR-ABL1 translocation.

References: [4] by NJ Charles · 2017 · Cited by 90 — Flow cytometry (FCM) is the primary method for blast immunophenotyping in clinical practice, and immunohistochemistry (IHC) and enzyme ... [5] by O. et al. · 2020 · Cited by 10 — Immunohistochemistry (IHC) is a primary method for blast immunophenotyping in clinical practice, and it can help identify the presence of BCR-ABL1 in MPAL. [6] An acute biphenotypic leukemia that is characterized by blasts that also carry the translocation t(9;22)(q34.1;q11.2) by karyotypic analysis or the BCR-ABL1 translocation by FISH or PCR. Mixed phenotype acute leukemia with BCR-ABL1 [10] For patients with confirmed mixed phenotype acute leukemia (MPAL), the pathologist or treating clinician should ensure that testing for t(9;22) ... statements Hematology Hematopathology Surgical pathology Histopathology Histology biomarker laboratory testing

Mixed Phenotype Acute Leukemia (MPAL) with BCR-ABL1 rearrangement is a rare and aggressive form of leukemia that requires prompt and effective treatment.

Current Treatment Recommendations

According to recent studies, the current treatment recommendation for MPAL with BCR-ABL1 involves an ALL-like induction regimen followed by allogeneic stem cell transplant (allo-sct) in the first complete remission [2][10]. This approach has shown promising results in achieving long-term survival and reducing relapse rates.

Targeted Therapies

Dasatinib, a second-generation tyrosine kinase inhibitor (TKI), has been effective in treating MPAL with BCR-ABL1. Studies have demonstrated that dasatinib can induce complete remission in patients who are refractory to other treatments [3]. Additionally, the combination of dasatinib and steroids has shown excellent short-term results for older adults [1].

Other Treatment Options

Ponatinib, another TKI, has been approved by the US Food and Drug Administration (FDA) for use in both chronic myeloid leukemia (CML) and BCR-ABL1-positive acute leukemias. While its efficacy in MPAL with BCR-ABL1 is not well established, it may be considered as a treatment option on a case-by-case basis [4].

Clinical Trials

Several clinical trials are currently recruiting participants to evaluate the safety and efficacy of various treatments for MPAL with BCR-ABL1. These include trials investigating dasatinib and ponatinib in combination with other therapies [5][6]. Patients may be eligible to participate in these studies, which can provide access to innovative treatments and contribute to advancing our understanding of this disease.

Initial Treatment

Initial treatment typically involves chemotherapy, which uses drugs that disrupt the growth of leukemia cells. The chemotherapy regimen may be tailored to the individual patient's needs and may include a combination of different medications [9].

References:

[1] O Wolach (2015) - For older adults, excellent short-term results have been obtained with dasatinib plus steroids and intrathecal chemotherpy.

[2] BS George (2022) - The current treatment recommendation is an ALL-like induction regimen followed by allogeneic stem cell transplant (allo-sct) in the first complete remission.

[3] C Kawajiri (2014) - Successful treatment of Philadelphia chromosome-positive mixed phenotype acute leukemia by appropriate alternation of second-generation tyrosine kinase inhibitors.

[4] T Carll (2020) - The TKI ponatinib, which has been approved by the US Food and Drug Administration for use in both chronic myeloid leukemia (CML) and BCR-ABL1-positive acute leukemias.

[5] Cortisone Recruiting Phase 1 Trials for B-cell Acute Lymphoblastic Leukemia / Mixed Phenotype Acute Leukemia (MPAL) / B Acute Lymphoblastic Leukemia With ...

[6] Dasatinib Recruiting Phase 1 Trials for B-cell Acute Lymphoblastic Leukemia / Mixed Phenotype Acute Leukemia (MPAL) / B Acute Lymphoblastic Leukemia With ...

[7] ABL001 taken in combination with dasatinib (Sprycel®) and prednisone (a steroid) as a possible treatment for MPAL with BCR-ABL1.

[8] Mixed-phenotype acute leukemia (MPAL) with t(9;22)(q34.1;q11.2) fulfills the criteria for MPAL and has blasts with t(9;22) and/or BCR-ABL1 rearrangement.

[9] Mar 14, 2023 - Initial treatment typically involves chemotherapy, which uses drugs that disrupt the growth of leukemia cells.

[10] BS George (2022) - The current treatment recommendation is an ALL-like induction regimen followed by allogeneic stem cell transplant (allo-sct) in the first complete remission.

Mixed phenotype acute leukemia (MPAL) with BCR-ABL1 can be challenging to diagnose, and it's essential to consider differential diagnoses to ensure accurate classification.

According to the search results, the differential diagnosis for de novo Ph+ acute leukemia includes:

• CML in BP (Blastic Phase)
• Ph+ B-LBL (Philadelphia chromosome-positive B-cell lymphoblastic leukemia)
• Ph+ MPAL (Philadelphia chromosome-positive mixed phenotype acute leukemia)

In addition to these conditions, it's also essential to consider other possibilities that may present with similar clinical and laboratory features. These include:

• Acute myeloid leukemia (AML) with a BCR-ABL1 fusion
• B-cell lymphoblastic leukemia/lymphoma (B-ALL/B-LHL) with a BCR-ABL1 fusion

To differentiate MPAL with BCR-ABL1 from these conditions, clinicians should consider the following:

• Immunophenotyping: This can help identify the presence of both myeloid and lymphoid markers in the leukemic blasts.
• Cytogenetic analysis: FISH or PCR can be used to detect the BCR-ABL1 fusion.
• Molecular testing: This can help identify other genetic abnormalities that may be present in the leukemia.

It's also worth noting that the diagnosis of MPAL with BCR-ABL1 requires a careful evaluation of the patient's clinical presentation, laboratory results, and histopathological findings. A multidisciplinary approach involving hematologists, pathologists, and molecular biologists is often necessary to ensure accurate classification and appropriate treatment.

References:

• [6] reports a case of acute leukemia with BCR-ABL1 that was initially suspected to be CML in BP.
• [5] describes the classification of BCR-ABL1–positive acute leukemia into three disease categories, including B-lymphoblastic leukemia (B-ALL).
• [9] provides an example of B/myeloid mixed-phenotype acute leukemia, BCR-ABL1 positive, with a heterogeneous population of blasts.
• [10] discusses the diagnosis and treatment of MPAL, highlighting the importance of accurate classification.