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Immunoglobulin Gene Sequence Analysis In Chronic Lymphocytic Leukemia: From Patient Material To Sequence Interpretation
Published on: November 26, 2018
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Immunoglobulin Gene Analysis in Chronic Lymphocytic Leukemia
Andreas Agathangelidis1, Richard Rosenquist2, Frederic Davi3
1Institute of Applied Biosciences, Center for Research and Technology, Thessaloniki, Greece.
Methods in Molecular Biology (Clifton, N.J.)
|October 24, 2018
Summary
Immunoglobulin (IG) gene rearrangements serve as crucial clonal markers in B-cell neoplasms. Analyzing these sequences, including somatic hypermutation (SHM) status, provides insights into B-cell development and prognostic value in diseases like chronic lymphocytic leukemia (CLL).
Area of Science:
- Immunology
- Molecular Biology
- Oncology
Background:
- B-cell receptor immunoglobulin (BcR IG) formation involves sequential VDJ and VJ gene recombination during B-cell development.
- Somatic hypermutation (SHM) and class-switch recombination (CSR) refine BcR IG function after antigen encounter.
- B-cell neoplasms originate from single transformed B cells, making IG gene rearrangements valuable clonal markers.
Purpose of the Study:
- To detail robust methodologies for reliable analysis of clonotypic IG gene rearrangement sequences.
- To provide a framework for interpreting IG sequence data, including SHM status, for B-cell neoplasms.
- To highlight the utility of IG sequences as clonal, developmental, and prognostic markers.
Main Methods:
- Isolation of peripheral blood mononuclear cells (PBMC).
- Identification of clonotypic IG gene rearrangements.
- Accurate interpretation of somatic hypermutation (SHM) status within rearranged IG heavy variable (IGHV) genes.
Main Results:
- Rearranged IG sequences are identical in neoplastic cells, serving as reliable clonal markers.
- IG gene configuration correlates with specific B-cell developmental stages.
- The SHM load in IGHV genes has prognostic and potentially predictive value, particularly in chronic lymphocytic leukemia (CLL).
Conclusions:
- Standardized and robust methods are essential for accurate IG sequence analysis.
- Clonotypic IG sequences offer multifaceted information regarding B-cell clonality, development, and disease prognosis.
- Expertise from initiatives like the European Research Initiative on CLL (ERIC) is crucial for reliable IG sequence analysis.
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