Related Experiment Video
Updated: Aug 21, 2025
10:26
In Vitro Differentiation Model of Human Normal Memory B Cells to Long-lived Plasma Cells
Published on: January 20, 2019
12.4K
PAX5 alterations in B-cell acute lymphoblastic leukemia
Zhilian Jia1,2, Zhaohui Gu1,2
1Department of Computational and Quantitative Medicine, Beckman Research Institute of City of Hope, Duarte, CA, United States.
Frontiers in Oncology
|November 17, 2022
Summary
Genetic alterations in the PAX5 gene are key drivers of B-cell acute lymphoblastic leukemia (B-ALL). Understanding these PAX5 mutations and their impact is crucial for developing targeted therapies for B-ALL.
Area of Science:
- Hematology
- Molecular Biology
- Oncology
Background:
- PAX5 is a critical regulator of B cell development and maintenance.
- Genetic alterations in PAX5 are frequently observed in B-cell acute lymphoblastic leukemia (B-ALL).
- These alterations include copy number variations, translocations, and point mutations, impacting B-ALL subtypes differently.
Purpose of the Study:
- To review recent advances in understanding PAX5 function in normal and malignant B cell development.
- To focus on PAX5 alterations as initiating or driver events in B-ALL.
- To highlight the heterogeneity of B-ALL driven by PAX5 lesions.
Main Methods:
- Review of recent large-scale genomic analyses of B-ALL.
- Analysis of mechanistic studies in human B-ALL and animal models.
- Examination of functional impacts of PAX5 variants, including haploinsufficiency and gain-of-function.
Main Results:
- PAX5 alterations are initiating events in B-ALL, leading to blocked B cell development and malignant transformation.
- Novel B-ALL subtypes driven by PAX5 genetic lesions have been identified, including those with specific mutations like PAX5 P80R.
- Altered PAX5 and deregulated genes contribute to disease heterogeneity and varied clinical outcomes.
Conclusions:
- PAX5 variants, alone or with other genetic lesions, are highly penetrant in driving B-cell malignancy.
- Understanding the diverse mechanisms driven by PAX5 alterations is essential for B-ALL treatment.
- Altered PAX5 and associated deregulated genes represent potential therapeutic targets in specific B-ALL cases.
Related Concept Videos
02:23Abnormal Proliferation
4.6K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.6K
01:31The Intrinsic Apoptotic Pathway
6.7K
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.7K
01:33Pleiotropy
40.8K
Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
40.8K
01:15Differentiation of Common Myeloid Progenitor Cells
3.3K
Common myeloid progenitors (CMPs) are oligopotent cells that can differentiate into granulocytes and macrophages. Granulocytes and macrophages are essential for protecting the body against bacterial, viral, or fungal infections. They migrate from the bone marrow into the circulating blood to reach specific tissue sites where they differentiate and help in immune surveillance. However, they survive only for a few days and must be continuously made available to the organism to maintain a robust...
3.3K
01:24B Cell Activation and Differentiation
3.9K
The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
3.9K