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VDJ-Seq: Deep Sequencing Analysis of Rearranged Immunoglobulin Heavy Chain Gene to Reveal Clonal Evolution Patterns of B Cell Lymphoma
Published on: December 28, 2015
Diagnostic value of clonality of surface immunoglobulin light and heavy chains in malignant lymphoproliferative
1Department of Pathology, Cox Institute, Wright State University School of Medicine, Dayton, Ohio 45429.
Insights
Assessing immunoglobulin light and heavy chain clonality is crucial for diagnosing B-cell malignancies like B-chronic lymphoid leukemia (B-CLL) and B-non-Hodgkin
Area of Science:
- Hematology
- Immunology
- Oncology
Background:
- Distinguishing B-cell malignancies from reactive conditions is critical for accurate diagnosis and treatment.
- Surface immunoglobulin (SIg) expression analysis, including light (L) and heavy (H) chain clonality, is a key diagnostic tool.
- Previous studies have focused on L-chain restriction, but the combined diagnostic value of L- and H-chain clonality requires further evaluation.
Purpose of the Study:
- To evaluate the diagnostic value of L- and H-chain clonality for B-chronic lymphoid leukemia (B-CLL) and B-non-Hodgkin's lymphoma (B-NHL).
- To assess the utility of combined L- and H-chain analysis in differentiating these malignancies from reactive lymphocytosis (RLC) and reactive lymphadenopathy (RLA).
Main Methods:
- Analysis of cell suspensions from peripheral blood and solid tissue samples.
- Quantification of monoclonal L-chain (mono-L) and monoclonal H-chain (mono-H) expression.
- Determination of cutoff levels for monoclonality.
- Comparison of clonality patterns in B-CLL, B-NHL, RLC, and RLA.
Main Results:
- High concordance of mono-L/mono-H patterns observed in both B-CLL (89.42%) and B-NHL (92.92%).
- Monoclonality of H chains proved complementary to L-chain restriction, particularly in cases with polyclonal or undetected L chains.
- No cases of RLC or RLA exhibited monoclonal SIg, indicating high specificity of the method for malignancy detection.
Conclusions:
- Combined assessment of SIg L- and H-chain clonality is a sensitive and specific method for diagnosing B-CLL and B-NHL.
- This approach effectively differentiates malignant B-cell proliferations from reactive conditions.
- Incorporating H-chain analysis enhances diagnostic accuracy, especially in challenging cases with atypical L-chain restriction patterns.
Abstract:
Cell suspensions from the peripheral blood of B-chronic lymphoid leukemias (B-CLL, n = 274) and reactive lymphocytosis (RLC, n = 132) and from solid tissue samples of B-non-Hodgkin's lymphoma (B-NHL, n = 466) and reactive lymphadenopathy (RLA, n = 324) were analyzed to evaluate the diagnostic value of clonality of L- and H- chains in B-CLL and B-NHL. Cutoff levels for monoclonal L-chain (mono-L) and monoclonal H-chain (mono-H) were defined. In B-CLL, the association patterns of L- and H- chains were as follows: mono-L/mono-H, 245 cases (89.42%); mono-L/polyclonal H chain (poly-H), 4 (1.46%); polyclonal L chain (poly-L)/mono-H, 2 (0.73%); poly-L/poly-H, 2 (0.73%); undetected (und)-L/mono-H, 6 (2.19%); and und-L/und-H, 15 (5.47%). In B-NHL, the association patterns were mono-L/mono-H, 433 cases (92.92%); mono-L/poly-H, 4 (0.86%); poly-L/mono-H, 8 (1.72%); poly-L/poly-H, 2 (0.43%); und-L/mono-H, 4 (0.86%); and und-L/und-H, 15 (3.22%). Monoclonality of H chains are complementary to L-chain restriction, especially in the cases with poly-L or und-L, and should be considered as a positive criterion in determining surface immunoglobulin (SIg) clonality. Monoclonality of SIg assessed by both L and H chains is both sensitive and specific for the diagnosis of B-CLL and B-NHL, and their differentiation from RLC and RLA, since none of the cases of RLC and RLA showed monoclonal SIg.
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