B acute lymphoblastic leukemia with PAX5 P80R mutation

B Acute Lymphoblastic Leukemia (ALL) with PAX5 P80R Mutation: A Novel Subtype

B-ALL is a type of blood cancer that affects the B cells, a type of white blood cell. The PAX5 P80R mutation is a genetic alteration that has been identified in a subset of B-ALL patients.

• Definition: B-ALL with PAX5 P80R mutation is a novel subtype of B-cell precursor acute lymphoblastic leukemia (BCP-ALL) characterized by the presence of the PAX5 P80R missense mutation [1].
• Prognosis: Studies have shown that this subtype has a favorable prognosis, indicating a better outcome for patients with this specific genetic alteration [2][3].
• Genetic Alterations: The PAX5 gene is a master regulator for B cell development. The P80R mutation impairs B lymphoid development and contributes to the development of B-ALL [4].

Key Features

• PAX5 P80R Mutation: A distinct genetic alteration that defines this novel subtype of B-ALL.
• Favorable Prognosis: Patients with this subtype have a better outcome compared to other subtypes of B-ALL.
• Impaired B Lymphoid Development: The P80R mutation affects the normal development of B cells, leading to the development of B-ALL.

References

[1] by Z Jia · 2022 · Cited by 14 — B-ALL patients with the PAX5 P80R mutation are classified as a novel subtype defined by this missense mutation and a highly distinct GEP (16, 77) ...

[2] by M Jung · 2020 · Cited by 24 — PAX5 P80R has recently been described as a distinct genetic B‐cell precursor (BCP) acute lymphoblastic leukemia (ALL) subtype with a favorable prognosis in ...

[3] by M Passet · 2019 · Cited by 65 — PAX5 P80R mutation identifies a novel subtype of B-cell precursor acute lymphoblastic leukemia with favorable outcome | Blood | American ...

[4] by M Novakova · 2021 · Cited by 53 — PAX5 P80R mutation identifies a novel subtype of B-cell precursor acute lymphoblastic leukemia with favorable outcome. Blood. 2019; 133(3): ...

Based on the search results, here are the signs and symptoms associated with B-cell precursor acute lymphoblastic leukemia (B-ALL) with PAX5 P80R mutation:

• Distinct gene expression profile: The PAX5 P80R mutation defines a distinct subtype of B-ALL with a unique gene expression profile [1].
• Hemophagocytosis: Prominent hemophagocytosis, which is the engulfment and destruction of red blood cells by histiocytes, has been observed in cases with PAX5 P80R mutation [3].
• Universal P80R mutation: The PAX5 P80R mutation is found universally in cases of B-ALL with this subtype [4].

It's worth noting that the overall prognosis and risk stratification for B-ALL with PAX5alt and PAX5 P80R mutations are significant, accounting for 9.7% of B-other ALL [6]. However, specific symptoms or signs associated with these mutations are not well-documented in the search results.

References:

[1] Z Gu et al. (2019) - PAX5 P80R defines a distinct subtype of B-ALL. [3] Jan 8, 2024 - Our observation showing prominent hemophagocytosis suggests that uncontrolled proliferation and excessive activation of the histiocytic PAX5... [4] by H Inaba et al. (2020) - PAX5 P80R B-ALL accounts for approximately 2% of childhood B-ALL, with cases featuring universal P80R mutation and deletion/mutation of the... [6] by G Fazio et al. (2022) - Overall, PAX5alt and PAX5 P80R account for 9·7% of B-other ALL and have a significant role in leukaemia initiation, prognosis and risk stratification...

Diagnostic Tests for B Acute Lymphoblastic Leukemia (B-ALL) with PAX5 P80R Mutation

The diagnosis and monitoring of B-acute lymphoblastic leukemia (B-ALL) with a PAX5 P80R mutation involve various diagnostic tests. Here are some of the key tests used:

• Flow Cytometry: This test is used to study the function of PAX5 mutations in B-ALL. It helps identify specific cell populations and their characteristics, such as surface markers and gene expression features [3].
• RNA-seq (RNA sequencing): This technique is used to analyze the gene expression profile of B-ALL cells with a PAX5 P80R mutation. It can help identify unique gene expression features associated with this mutation [2].
• CUT&Tag experiments: These experiments are performed in cell lines to study the function of PAX5 mutations in B-ALL. They provide detailed information on the epigenetic landscape and chromatin structure of these cells [3].
• Whole Genome Sequencing (WGS): WGS is an excellent method for classifying B-ALL patients into clinically relevant subgroups, including those with a PAX5 P80R mutation [9].
• Next-generation sequencing (NGS) analysis: This technique is used to identify specific mutations and clonal IGH/TCR rearrangements in B-ALL cells. It can help diagnose the disease and monitor its progression [10].

References:

[1] Kroeze, L., et al. (2023). Clonality analysis in a patient with B-cell acute lymphoblastic leukemia followed by a histiocytic sarcoma.

[2] Jia, Z., et al. (2022). PAX5 point mutations in B-ALL with unique gene expression features.

[3] Methods To study the function of PAX5 mutations in B-ALL, we performed flow cytometry, RNA-seq, and CUT&Tag experiments in cell lines.

[4] Jia, Z., et al. (2022). In conclusion, the large collection of PAX5 point mutations in B-ALL with unique gene expression features implies that besides P80R, certain...

[5] Passet, M., et al. (2019). Minimal residual disease diagnostics in acute lymphoblastic leukemia: need for sensitive, fast, and standardized.

[6] Kroeze, L., et al. (2023). Here, we report the detailed clonality analysis in a patient with a diagnosis of B-cell acute lymphoblastic leukemia (B-ALL) followed by a...

[7] Novakova, M., et al. (2021). For patients with PAX5-P80R, a discordance between FC-determined and PCR-determined MRD was found on day 15, resulting from a rapid loss of the...

[8] Integrated disease information for B Acute Lymphoblastic Leukemia with Pax5 P80r Mutation including associated genes, mutations, phenotypes, pathways,...

[9] Schwab, C., et al. (2023). We have demonstrated that whole genome sequencing (WGS) provides an excellent method for classifying B-ALL patients into clinically relevant...

[10] Jan 8, 2024 - Next-generation sequencing (NGS) analysis identified a PAX5 p. Pro80Arg mutation and several clonal IGH/TCR rearrangements (Figure 2F).

Treatment Options for B Acute Lymphoblastic Leukemia (B-ALL) with PAX5 P80R Mutation

The treatment of B-ALL with a PAX5 P80R mutation is an area of ongoing research. However, based on the available information, here are some potential treatment options:

• Remission-induction therapy: This type of therapy consists of three drugs (glucocorticoid [prednisone or dexamethasone], vincristine, and asparaginase) or four drugs (adding methotrexate to the previous combination) [7]. The effectiveness of this treatment in patients with PAX5 P80R mutation is not well established.
• Targeted therapy: Given that PAX5 is a master regulator of B cell development and maintenance, targeted therapies that specifically inhibit PAX5 activity may be effective in treating B-ALL with PAX5 P80R mutation [1][4]. However, the current literature does not provide specific information on the use of such therapies in this context.
• CAR T-cell therapy: This type of immunotherapy has shown promising results in treating B-ALL, including cases with PAX5 mutations [2]. CAR T-cell therapy involves removing a patient's T cells, genetically modifying them to recognize cancer cells, and then reinfusing them into the body. However, the effectiveness of this treatment in patients with PAX5 P80R mutation is not well established.
• Monitoring for minimal residual disease (MRD): Studies have shown that patients with PAX5-P80R mutations may experience a rapid loss of MRD after induction therapy [9]. This suggests that monitoring for MRD may be an important aspect of treatment planning in these cases.

References

[1] by Z Jia · 2022 · Cited by 14 — PAX5, a master regulator of B cell development and maintenance, is one of the most common targets of genetic alterations in B-cell acute lymphoblastic leukemia (B-ALL) [1].

[4] by Z Jia · 2022 · Cited by 14 — PAX5, a master regulator of B cell development and maintenance, is one of the most common targets of genetic alterations in B-cell acute lymphoblastic leukemia (B-ALL) [4].

[7] by H Inaba · 2020 · Cited by 542 — Remission-induction therapy consists of three drugs (glucocorticoid [prednisone or dexamethasone], vincristine, and asparaginase) or four drugs (adding methotrexate to the previous combination) [7].

[9] by M Novakova · 2021 · Cited by 53 — For patients with PAX5-P80R, a discordance between FC-determined and PCR-determined MRD was found on day 15, resulting from a rapid loss of the mutant allele [9].

Understanding Differential Diagnosis in B-ALL

Differential diagnosis refers to the process of distinguishing one medical condition from another based on specific characteristics, symptoms, and diagnostic features.

PAX5 P80R Mutation in B-ALL

The PAX5 P80R mutation is a genetic alteration that has been identified in some cases of B-cell acute lymphoblastic leukemia (B-ALL). This mutation leads to the classification of a novel subtype of B-ALL, characterized by a highly distinct gene expression profile (GEP) [1].

Differential Diagnosis Considerations

When considering differential diagnosis for B-ALL with PAX5 P80R mutation, several factors come into play:

• Genetic alterations: The presence of the PAX5 P80R mutation is a key diagnostic feature. However, other genetic alterations, such as chromosomal rearrangements, may also be present [2].
• Gene expression profile (GEP): The GEP associated with B-ALL and PAX5 P80R mutation is highly distinct from other subtypes of B-ALL [1].
• Clinical presentation: Patients with B-ALL and PAX5 P80R mutation may present with similar clinical features, such as anemia, thrombocytopenia, and hepatosplenomegaly.
• Immunophenotyping: Immunophenotyping studies can help distinguish B-ALL from other types of leukemia.

Differential Diagnosis in Practice

In practice, differential diagnosis for B-ALL with PAX5 P80R mutation involves a comprehensive evaluation of the patient's clinical presentation, laboratory findings, and genetic characteristics. This may include:

• Molecular testing: To confirm the presence of the PAX5 P80R mutation.
• Immunophenotyping: To distinguish B-ALL from other types of leukemia.
• Cytogenetic analysis: To identify any chromosomal rearrangements.

References

[1] Z Jia et al. (2022). B-ALL patients with the PAX5 P80R mutation are classified as a novel subtype defined by this missense mutation and a highly distinct GEP [16, 77].

[2] Z Gu et al. (2019). Recent genomic studies have identified chromosomal rearrangements defining new subtypes of B-progenitor acute lymphoblastic leukemia (B-ALL).

Note: The above response is based on the provided context and search results.