Methods and materials for monitoring myeloma using quantitative mass spectrometry

Abstract

The subject invention concerns methods and materials for diagnosing, monitoring the progress, and / or providing a prognosis for multiple myeloma and other conditions associated with antibody production in a person or animal. The methods o f the invention utilize mass spectrometry for quantitative monitoring and detection of antibody produced by the plasma cells. The methods of the invention can be utilized for diagnosis, monitoring, and / or prognosis of multiple myeloma, monoclonal gammopathy, and other immunological or hematological conditions and disorders. In addition to detecting and quantifying antibody in a sample, other biological markers, such as serum albumin and / or beta-2-microglobulin, can also be detected and quantified using the present invention, and in combination with detection and quantification of antibody. Thus, in one embodiment, both antibody and serum albumin and / or beta-2-microglobulin are detected and quantified using mass spectrometry and a diagnosis or prognosis made based on the results and levels detected.

Description

CROSS-REFERENCE TO RELATED APPLICATION[0001]The present application claims the benefit of U.S. Provisional Application Ser. No. 61 / 076,907, filed Jun. 30, 2008, which is hereby incorporated by reference herein in its entirety, including any figures, tables, nucleic acid sequences, amino acid sequences, and drawings.BACKGROUND OF THE INVENTION[0002]Multiple myeloma (MM) is a cancer of the plasma cell, which primarily develops in the elderly population. The progression of the tumor is well understood, and it can be diagnosed by the presence of multiple myeloma cells in the bone marrow and monitored by the amount of antibody secretion from the clonal population of plasma cells. A premalignant condition known as monoclonal gammopathy of undetermined significance (MGUS) develops at certain rates in the U.S. population: 3% at age 50, 5% at age 70, and 7% by age 85; approximately 1% of MGUS patients progress to multiple myeloma on an annual basis (Kyle et al., 2006). The molecular causes f...

AI Technical Summary

Benefits of technology

[0006]In one embodiment of a method of the invention, monoclonal antibody proteins were excised from serum protein electrophoresis gels and digested with trypsin. Following trypsin digestion, the resulting isolated proteolytic peptides were sequenced with liquid chromatography coupled to tandem mass spectrometry. Using the results from several patient samples, specific peptides were selected to monitor each type of antibody (A, D, E, G, and M), as well as kappa and lambda light chain and other diagnostic molecules like serum albumin and beta-2-microglobulin (see Table 1). After selecting peptides that were consistently detected in all patient samples, a quantitative assay was developed using liquid chromatography coupled to multiple reaction monitoring (LC-MRM) on a tr

Problems solved by technology

Despite the highly specific and easily detectable biomarkers, many challenges still exist for MM treatment.

Patient monitoring strategies present significant challenges, particularly in the detection of MGUS patients most likely to develop multiple myeloma and ongoing assessment of relapse or recurrence in previously treated multiple myeloma patients.

Many MM patients who have undergone treatment are repetitively checked at two week or four week intervals, leading to high numbers of clinic visits and collection of large volumes of blood.

Images