Evidence of serum immunoglobulin abnormalities up to 9.8 years before diagnosis of chronic lymphocytic leukemia: a prospective study

Tsai, Huei‐Ting; Caporaso, Neil E.; Kyle, Robert A.; Katzmann, Jerry A.; Dispenzieri, Angela; Hayes, Richard B.; Marti, Gerald E.; Albitar, Mäher; Ghia, Paolo; Rajkumar, S. Vincent; Landgren, Ola

doi:10.1182/blood-2009-08-237651

Cited by 73 publications

(65 citation statements)

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“…Additionally, in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, a polyclonal increase in the serum FLC concentration was associated with an increased risk of chronic lymphocytic lymphoma (CLL). This association was present up to 9 years prior to the diagnosis of CLL but became stronger closer to the time of diagnosis (14 ).…”

Section: Polyclonal Flcs As a Clinically Relevant Biomarkermentioning

confidence: 86%

Polyclonal Immunoglobulin Free Light Chains as a PotentialBiomarker of Immune Stimulation and Inflammation

Hutchison

Landgren

2011

Clinical Chemistry

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Section: Polyclonal Flcs As a Clinically Relevant Biomarkermentioning

confidence: 86%

Polyclonal Immunoglobulin Free Light Chains as a PotentialBiomarker of Immune Stimulation and Inflammation

Hutchison

Landgren

2011

Clinical Chemistry

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“…protein electrophoresis, respectively. In stored prediagnostic blood from 109 persons who subsequently developed CLL, the prevalence of an abnormal FLC ratio, Mprotein, and hypogammaglobulinemia before CLL diagnosis was 38% (95% confidence interval, 29%-47%), 13% (7%-21%), and 3% (1%-8%), respectively (58). In fact, Mproteins and abnormal FLC ratios were detected up to 9.8 years before CLL diagnosis in a total of 48 persons (44%).…”

Section: Future Directionsmentioning

confidence: 96%

“…Hypogammaglobulinemia was not present until 3 years before the diagnosis of CLL. Among 37 patients with information on tumor cell immunophenotype, an association between immunophenotype and involved FLC (P ¼ 0.024) was observed (58). Prospective studies on the natural history of coexisting MBL and monoclonal gammopathies should help illuminate the complex relationships among B-cell malignancies and their precursors.…”

Section: Future Directionsmentioning

confidence: 97%

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Prevalence, clinical aspects, and natural history of IgM MGUS

McMaster

Landgren

2010

Cytometry Part B Clinical

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Results: There appears to be marked heterogeneity in the prevalence of IgM MGUS across populations. However, studies have varied in definition, design, laboratory methods, and endpoints. IgM MGUS differs from non-IgM MGUS in certain respects, including prevalence across racial groups, rate of progression, and pattern of malignant outcomes. There are limited data regarding the coincident occurrence of IgM MGUS and MBL.Conclusions: Future studies incorporating both protein electrophoresis and flow cytometry are needed to define the underlying spectrum and causes of precursor development, risk factors for progression, and markers that distinguish low-and high-risk precursor patients. Published

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“…In a study of eight chronic lymphocytic leukemia (CLL) patients, an Mprotein was detectable in six individuals only by the serum FLC assay and not by standard SPEP/IFE [29]. A prospective study found that FLC levels may be abnormal nearly 10 years before a diagnosis of CLL is made, suggesting that their production may represent an early event in the pathogenesis of the disease [30]. Other emerging data suggest that an abnormal FLC ratio confers a worse prognosis in CLL patients, and may actually identify a biologically distinct subgroup of the disease [31,32].…”

Section: Clinical Applicationsmentioning

confidence: 99%

Serum free light chain analysis

2010

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In a variety of hematologic malignancies, immunoglobulin light chains (LC) are overproduced clonally and circulate without being linked by disulphide bonds to the immunoglobulin heavy chain. The recent development of a robust assay known as j and k ''free'' LC (FLC) to quantify the levels of these unbound LC in the serum, and thereby determine their ratio, has led to an explosion of studies that demonstrate its utility in a wide range of hematologic disorders. This article summarizes laboratory testing for serum FLC, with a particular focus on clinical applications for the test. Am. J. Hematol. 85:787-790, 2010. V V C 2010 Wiley-Liss, Inc. BackgroundHematologic malignancies frequently result in the production of monoclonal immunoglobulin. Detection of both intact immunoglobulin and immunoglobulin free light chains (FLC) in the urine and blood has proven to be valuable in the diagnosis, prognosis, and monitoring of treatment of these diseases. One particularly useful property of serum FLC is their short half-life in the blood (j, 2-4 hrs; k, 3-6 hrs) in comparison to intact immunoglobulin (21 days), which provides an opportunity for real-time monitoring of disease progression and response to treatment.For well over a century, testing for the presence of Bence Jones (BJ) protein in the urine was considered to be the gold standard to assess the clonally abnormal levels of immunoglobulin FLC. This technique can detect FLC down to the range of 10-40 mg/L; however, it can be challenging to obtain an accurate 24 hr urine collection, which is necessary for the test [1]. Moreover, due to the high resorptive capabilities of the proximal tubules of the kidney or reduced renal function, patients with low levels of FLC in the serum may not have detectable amounts in the urine [2]. Quantitative alterations of serum immunoglobulins (Igs) may result from polyclonal or monoclonal disorders. The combination of serum protein electrophoresis (SPEP), immunofixation (IFE), and densitometric analysis permits characterization and quantitation of the monoclonal immunoglobulin; however, the sensitivity of SPEP to detect FLC is poor, with a lower limit of sensitivity of 500-2,000 mg/L. Although the IFE does improve sensitivity for the detection of FLC (lower limit of sensitivity 150-500 mg/L), it is a more time-intensive assay and does not allow for quantification. Technical Aspects, Performance, and LimitationsThe development of an accurate and reproducible serum assay to determine j and k FLC concentration with high sensitivity has been a major challenge. A significant barrier to the development of the test is the fact that the unique epitope that is a marker of FLC is ''hidden'' or concealed in the conformational structure of an intact Ig. This precluded the development of a tool such as a specific antibody to detect the ''hidden epitope'' of FLC. This barrier was overcome in 2001 by Bradwell and coworkers [3], who dissociated the FLC from heavy chains and then raised polyclonal antibodies to detect the unique epitopes on j and k LC. T...

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Evidence of serum immunoglobulin abnormalities up to 9.8 years before diagnosis of chronic lymphocytic leukemia: a prospective study

Abstract: Immune-related deficiencies are wellknown complications of chronic lymphocytic leukemia (CLL).

Cited by 73 publications

References 28 publications

Polyclonal Immunoglobulin Free Light Chains as a PotentialBiomarker of Immune Stimulation and Inflammation

Polyclonal Immunoglobulin Free Light Chains as a PotentialBiomarker of Immune Stimulation and Inflammation

Prevalence, clinical aspects, and natural history of IgM MGUS

Serum free light chain analysis

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