High incidence of monoclonal proteins in the serum and urine of chronic lymphocytic leukemia patients

Abstract

Chronic lymphocytic leukemia (CLL) is generally considered a nonsecretory B cell immunoproliferative disorder. Conventional electrophoretic and immunoelectrophoretic methods have revealed serum monoclonal proteins in less than 10% of these patients. However, there is increasing experimental evidence from in vitro studies demonstrating that CLL cells may secrete immunoglobulins, particularly free light chains. We examined the serum and urine of 36 consecutive CLL patients for monoclonal proteins using sensitive immunochemical methods (high resolution agarose gel electrophoresis combined with immunofixation). The results obtained were correlated with the Rai stage, quantitative immunoglobulin levels, and lymphocyte membrane immunoglobulin phenotype of the leukemic cells. Twenty-three monoclonal proteins were identified in the serum or urine of 22 patients, an incidence of 61%. Six patients had serum monoclonal proteins, seven had only urinary monoclonal proteins, and nine had monoclonal proteins in serum and urine. In every instance the monoclonal protein was the same light chain type as expressed on the leukemic cells. Our findings suggest that the monoclonal proteins observed in the serum or urine of CLL patients are secretory products of the tumor cells and that their discovery is a function of the sensitivity of the method used for their detection.

Frequent discordance of the light-chain isotypes expressed by serum monoclonal components and leukaemic B-cells

“…Aberrant expression of j-MC in k leukaemias was seen in six cases. In the series of Deegan et al (1984), PP and leukaemic cells were always of the same LC isotype. Garand et al (2000) reported a single case of biclonal j + k PP in one j lymphoplasmacytoid leukaemia.…”

“…Biclonal gammopathy seems to be more frequent in leukaemic B malignancies, comprising 13% of our PP cases, than in MGUS or myeloma, in which the frequency is classically reported as 1-3.5% (Van Hoof, Rombouts & Lepoutre, 1989;Osterborg, Hansson & Mellstedt, 1996). In the series of Deegan et al (1984), only one case of biclonality was found. In the series of secreting lymphoplasmacytoid leukaemias reported by Garand et al (2000), one biclonal j + k PP was found in one j leukaemia.…”

“…A 30% incidence was observed in our series of various B-cell leukaemias. In a report of 22 Bcell CLLs (Deegan et al, 1984), 68% had a MC in serum and 73% in urine. It should be noted that the latter series was published before the definition of stringent diagnostic criteria in the 1990s, and CLL could only be regarded as a probable diagnosis.…”

Monoclonal free light chains in urine and their significance in clinical diagnostics: Are they really tumor markers?

“…It can be observed in many types of lymphoproliferative diseases classified as so-called nonsecretory lymphoid tumours. According to earlier reports, the incidence of component M in serum and/or urine NHL patients is about 10% (29,30).…”

Free light chain: a novel predictor of adverse outcome in chronic lymphocytic leukemia

“…However, the major drawback, limiting routine clinical use of these parameters, is the cost and complexity of technical procedures, underlying the necessity for further standardization. With this increased awareness, the focus of research has moved toward new simple prognostic markers allowing widespread clinical practice.Although monoclonal protein secretion is a typical feature of plasma cell dyscrasias, it can also be detected in other B cell malignancies including CLL (8,9). An abnormal free light chain ratio (FLCR), which was reported in 44% of patients with CLL, has proven to be predictive for progression of monoclonal gammopathy of uncertain significance, solitary plasmacytoma of bone, amyloidosis, multiple myeloma (MM), Waldenstro¨m's macroglobulinemia, and smoldering MM (9-16).…”