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Updated: Jul 2, 2026
Immunoglobulin Gene Sequence Analysis In Chronic Lymphocytic Leukemia: From Patient Material To Sequence Interpretation
Published on: November 26, 2018
The immunodeficiency of chronic lymphocytic leukaemia
1Cancer Sciences Division, University of Southampton, Southampton, UK.
Insights
Patients with chronic lymphocytic leukaemia (CLL) experience progressive immunodeficiency, with infections being a leading cause of death. Research is ongoing to understand and address this complex immune dysfunction and its treatment implications.
Area of Science:
- Immunology
- Oncology
- Cell Biology
- Genetics
Background:
- Patients with chronic lymphocytic leukaemia (CLL) suffer from progressive immunodeficiency, making infections the primary cause of mortality.
- This review examines the extent, causes, clinical significance, and potential remedies for immune dysfunction in CLL.
Purpose of the Study:
- To review the literature on immunodeficiency in chronic lymphocytic leukaemia (CLL).
- To identify the extent, causes, clinical significance, and potential remedies for immune abnormalities in CLL patients.
Main Methods:
- Comprehensive literature review of all available papers on CLL since 1970, including historical and related immunology, cell biology, oncology, and genetics articles.
- Analysis of data from major CLL conferences and weekly PubMed/Science Direct updates.
- Synthesis of expert knowledge accumulated over 40 years of CLL research.
Main Results:
- Immunodeficiency in CLL involves all immune system components, primarily manifesting as hypogammaglobulinaemia.
- Tumor cell infiltration and cytokine secretion by tumor cells suppress immunity and sustain the tumor.
- CLL treatments generally exacerbate immunodeficiency; while intravenous immunoglobulin is effective, it's not cost-effective, and prophylactic antibiotics are situationally useful. Vaccinations are typically ineffective.
Conclusions:
- Tumor-stromal interactions are a critical area of ongoing research in CLL.
- Development of improved vaccination strategies and more cost-effective, convenient antimicrobial prophylaxis for opportunistic infections in CLL patients is needed.
Introduction:
Patients with chronic lymphocytic leukaemia (CLL) have progressive immunodeficiency and infection is the commonest cause of death. This review seeks to identify the extent of the abnormality, its cause, clinical significance and any possible remedy.
Sources Of Data:
TJH has studied CLL for the past 40 years and has scanned or read every paper he could find published on the topic since 1970 and most of those of historical importance published before that date. He has read around the subject, covering relevant articles on immunology, cell biology, oncology and genetics. Furthermore, he has attended most major meetings dealing with CLL in this time and has written many reviews to update the state of knowledge about the topic. He receives weekly updates of papers published on CLL from PubMed and Science Direct with the keywords 'chronic lymphocytic leukaemia'.
Areas Of Agreement:
The immunodeficiency chiefly manifests as hypogammaglobulinaemia but involves all elements of the immune system. It is caused by the interpolation of tumour cells among immunological cells and mediated by bi-directional cell contact and secretion of cytokines, which both sustain and invigorate the tumour and suppress immunity. CLL treatment generally makes the immunodeficiency worse. Intravenous immunoglobulin is clinically effective but not cost-effective, while prophylactic antibiotics are useful in appropriate circumstances. Vaccination against infectious disease is usually ineffective.
Areas Of Controversy:
Exactly how the presence of tumour cells in the immune organs renders the patient immunodeficient is controversial as is the clinical significance of minor degrees of immunodeficiency in early or indolent cases. The immunosuppressive effect of most forms of treatment is agreed, but how much this should figure in the choice of treatment is a matter of dispute.
Growing Points:
The study of tumour-stromal interactions is an area of intense research.
Areas Timely For Developing Research:
There has been little done to develop better vaccination strategies in patients with CLL, and although effective antimicrobials have been developed to protect against opportunistic infections, many are both expensive and inconvenient. More work is necessary to define precisely which patients should be offered them and when.
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