Lab Med Online.  2014 Jul;4(3):125-131. 10.3343/lmo.2014.4.3.125.

Clinical Significance of Clonal Rearrangement of the Immunoglobulin Gene in the Bone Marrow of Patients with B-cell Non-Hodgkin Lymphoma

• Kim JH
• Lee JY
• Son JA
• Song SA
• Oh SH
• Shin JH
• Kim HR
• Jun KR
• Lee JN

• KMID: 1706848
• DOI: http://doi.org/10.3343/lmo.2014.4.3.125

Abstract

BACKGROUND
In the early stages of non-Hodgkin lymphoma (NHL), it can be difficult to recognize minimal morphological changes in the bone marrow (BM). In particular, when the quality of the BM biopsy is poor, determining BM involvement is limited to microscopic findings on BM aspiration. In this study, we compared the results of clonal immunoglobulin (IG) gene rearrangements with BM morphology results in B-cell NHL patients who underwent BM analysis as a staging workup and evaluated the usefulness of the clonal IG gene rearrangements for staging.
METHODS
Forty two B-cell NHL patients were analyzed. Clonal rearrangements of the IG heavy chain (IGH), kappa light chain (IGK) and lambda light chain (IGL) genes were detected using the IdentiClone(TM) Clonality assay (InVivoScribe Technologies, USA). Clinical characteristics and outcomes were evaluated based on the detection of monoclonal IG gene rearrangements.
RESULTS
Monoclonal IG gene rearrangements were found in 9 of 42 patients (21.4%). Microscopic BM involvement was found in only 2 of 42 patients (4.8%). The monoclonality rate of IG genes in BM was correlated with clinical stage and the international prognostic index (P<0.01). Patients with monoclonal IG gene rearrangements in BM had a significantly higher relapse rate (P=0.014) and poorer overall survival at 2 yr (P<0.01).
CONCLUSIONS
Clonality analysis of BM in B-cell NHL can contribute to identification of patients with occult BM involvement with a significantly poorer overall survival despite normal BM histology.

Keyword

Non-Hodgkin lymphoma; B-cell; B-lymphocyte; Bone marrow; Gene rearrangement

MeSH Terms

B-Lymphocytes*
Biopsy
Bone Marrow*
Gene Rearrangement
Genes, Immunoglobulin*
Humans
Immunoglobulins
Lymphoma, Non-Hodgkin*
Recurrence
Immunoglobulins

Figure

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  Fig. 1 Clonality analysis of immunoglobulin gene rearrangement in B-cell NHL using BIOMED-2 protocol. (A) Polyclonal rearrangement of IGK framework region. (B-D) Monoclonal rearrangement of IGH, IGK, and IGL framework regions. Abbreviations: NHL, non-Hodgkin lymphoma; IGH, immunoglobulin heavy chain; IGK, immunoglobulin κ light chain; IGL, immunoglobulin λ light chain.

• 

  Fig. 2 Kaplan-Meier curves of overall survival of patients according to the detection of monoclonal immunoglobulin gene rearrangements (IgR) in bone marrow.

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  Fig. 3 Kaplan-Meier curves of overall survival of patients according to involvement of bone marrow in positron emission tomography (PET) and the detection of immunoglobulin gene rearrangements (IgR).

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