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Updated: Jul 12, 2026
Immunoglobulin Gene Sequence Analysis In Chronic Lymphocytic Leukemia: From Patient Material To Sequence Interpretation
Published on: November 26, 2018
Long-term evaluation of three multiple-case Waldenstrom macroglobulinemia families
Mary L McMaster1, Gyorgy Csako, Therese R Giambarresi
1Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, NIH, Department of Health and Human Services, 6120 Executive Boulevard, MSC 7236. Bethesda, MD 20892-7236, USA. mcmastem@mail.nih.gov
Purpose:
Because the clinical significance of immunoglobulin abnormalities reported in relatives of familial Waldenström macroglobulinemia (WM) patients is unknown, we initiated a follow-up study of three WM families originally evaluated 27 years previously.
Experimental Design:
Of 29 eligible first-degree relatives of WM patients, 27 (93%) had originally participated in clinical and electrophoretic evaluations. We re-contacted all participants for prospective follow-up electrophoretic analysis and other studies.
Results:
Initially, five relatives had IgM monoclonal gammopathy (IgM MG), and four had IgM polyclonal gammopathy (PG). Twenty-two relatives (81%) were re-evaluated. Median follow-up was 17 years (range, 7-27). At re-contact, all IgM MG persisted or progressed, including three that evolved to WM. Among the four with PG, two new IgM MG cases developed. Overall, seven relatives (26%) had IgM MG, and five (18%) had IgM PG.
Conclusions:
Although based on small numbers, this study provides the longest comprehensive follow-up of WM families to date. IgM MG seems to be a phenotypic marker of WM susceptibility in some families and may have a high risk of progression to WM. IgM PG may also be important in WM families. These observations require validation in larger studies and, if confirmed, may be used to identify a cohort (relatives with IgM MG) for future prevention strategies.
Insights
This study followed Waldenström macroglobulinemia (WM) families for 27 years. Immunoglobulin abnormalities, like IgM monoclonal gammopathy, persisted or progressed, with some evolving to WM, indicating potential susceptibility markers.
Area of Science:
- Hematology
- Oncology
- Genetics
Background:
- Familial Waldenström macroglobulinemia (WM) is a rare B-cell lymphoproliferative disorder.
- The clinical significance of immunoglobulin abnormalities in WM relatives is not well understood.
- Longitudinal studies are needed to clarify the natural history of these abnormalities in familial settings.
Purpose of the Study:
- To investigate the long-term clinical significance of immunoglobulin abnormalities in relatives of patients with familial Waldenström macroglobulinemia (WM).
- To re-evaluate participants from a previous study conducted 27 years prior.
- To determine the progression and evolution of immunoglobulin abnormalities within WM families.
Main Methods:
- Prospective follow-up study of first-degree relatives from three WM families.
- Re-contact and electrophoretic analysis of participants originally evaluated 27 years ago.
- Inclusion of 27 out of 29 eligible relatives (93%) in the follow-up evaluations.
Main Results:
- Initially, five relatives had IgM monoclonal gammopathy (IgM MG) and four had IgM polyclonal gammopathy (PG).
- After a median follow-up of 17 years, all initial IgM MG cases persisted or progressed, with three evolving to WM.
- Two new IgM MG cases developed from the PG group, resulting in seven relatives (26%) with IgM MG and five (18%) with IgM PG at follow-up.
Conclusions:
- Immunoglobulin abnormalities, particularly IgM monoclonal gammopathy (IgM MG), may serve as phenotypic markers for Waldenström macroglobulinemia (WM) susceptibility within families.
- There appears to be a significant risk of progression from IgM MG to WM.
- IgM polyclonal gammopathy (PG) might also play a role in WM families, warranting further investigation and validation in larger cohorts for potential prevention strategies.