Correlation of LPL and ADAM29 Gene Expression with Mutational Status of IGVH Genes in Chronic Lymphocytic Leukemia
Ana Lucia Cota, Domnita Crisan. William Beaumont Hospital, Royal Oak, MI
Background: Chronic lymphocytic leukemia (CLL) has a very variable clinical course and survival. Many biomarkers have been studied in an effort to predict prognosis and response to therapy. The most accurate prognosis predictor of is the mutational status of the immunoglobulin heavy chain gene variable region (IGVH). However, IGVH mutational status assays are highly complex and expensive. Previous gene expression studies in CLL have shown differential expression of several genes between mutated (good prognosis) versus unmutated (poor prognosis) cases. Our goal is to evaluate the association of gene expression for lipoprotein lipase (LPL) gene and metalloproteinase 29 (ADAM29) gene with IGVH mutational status in CLL patients, and ultimately use the LPL/ADAM29 expression ratio as surrogate for IGVH mutational status.
Design: CLL patients were identified from Beaumont Hospital records from January 2008 to June 2012. Molecular analysis was performed on 65 cases. IGVH mutational status analysis was performed on DNA isolated from peripheral blood using the Invivoscribe Technologies IGH somatic hypermutation assay. The degree of homology to the germline VH sequence is expressed as % value. Gene expression analysis was performed on RNA isolated from peripheral blood, with reverse transcription to generate cDNA and PCR performed to detect LPL and ADAM29 transcripts, and reporting the expression ratio. For the statistical analysis, we used SAS for Windows, version 9.3.
Results: Of the 65 patients studied, 44 had mutated IGVH (< 98% homology) and 21 had unmutated IGVH (>98% homology). Of the mutated cases, 31 had an LPL/ADAM29 ratio of <1, and 8 had a ratio of 1. Of the unmutated cases, 20 have an LPL/ADAM29 ratio of >1 and 1 had a ratio of 1 (see Table 1). The sensitivity of the LPL/ADAM29 gene expression testing is 88.6%, specificity 100%, positive predictive value 100%, and negative predictive value 83.3%.
Conclusions: It is well documented that overexpression of LPL is present in CLL, and an underexpression of ADAM29 is seen. In the present study we determined the LPL/ADAM29 ratio and compared the results to the IVGH mutational status. Gene expression testing for LPL/ADAM29 ratio has a high sensitivity and specificity, and could be used as a surrogate test for IVGH mutational status for prognosis evaluation. The LPL/ADAM29 ratio testing is a faster, less expensive and less labor intensive method that could be used as a surrogate test, and can accurately separate patients with mutated and unmutated IGVH status.
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 235, Wednesday Afternoon