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Chapter: Medical Immunology: Malignancies of the Immune System

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Chronic Lymphocytic Leukemia

Chronic lymphocytic leukemia is, in the vast majority of cases, a B-cell malignancy and has many features in common with Waldenström’s macroglobulinemia: it is a disease of old age, often with a relatively benign course.

Chronic Lymphocytic Leukemia

Chronic lymphocytic leukemia is, in the vast majority of cases, a B-cell malignancy and has many features in common with Waldenström’s macroglobulinemia: it is a disease of old age, often with a relatively benign course. Central to its pathogenesis seems to be an overexpression of the bcl-2 gene, which inhibits apoptosis.

Clinical symptoms are often absent or very mild. Malaise, fatigue, or enlargement of the lymphoid tissues felt by the patient are the most frequent presenting complaints. Phys-ical diagnosis shows enlargement of the lymph nodes, spleen, and liver. Viral infections, such as herpes and herpes zoster, and fungal infections are frequent in these patients, point-ing to a T-cell deficiency, which is confirmed by the finding of reduced numbers of T cells and reduced responses to T-cell mitogens. The prognosis is determined by the frequency of severe opportunistic infections.

Diagnosis requires confirmation of the lymphocytic nature of the proliferating cells. This can be done by conventional morphology, but to prove that the proliferating cells are B lymphocytes, additional tests are required, such as:

·              Detection of monoclonal immunoglobulins in serum and/or urine.Bence Jones pro-teins can be detected in the concentrated urine of approximately one third of the patients. Rarely, IgM monoclonal proteins may be detected in serum. Most pa-tients are hypogammaglobulinemic.

·              Detection of cell-associated immunoglobulins.About 98% of the patients carry mon-oclonal IgM on the membrane of the leukemic cells. In some cases, cytoplas-mic retention of immunoglobulins can also be demonstrated.

·              Identification of B-cell membrane markers.The membrane markers of the leukemiccells are identical to those of mature B cells, with the following exceptions: CD11a/18 and CD22 are not expressed, while CD5  is ex-pressed in over 85% of the cases.


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