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Published on: July 20, 2016
The predictive value of lipoprotein lipase for survival in chronic lymphocytic leukemia
Mars B van't Veer1, Anne M Brooijmans, Anton W Langerak
1Department of Hematology, Erasmus MC, Rotterdam, The Netherlands. m.vantveer@erasmusmc.nl
Insights
Lipoprotein lipase (LPL) gene expression predicts survival in chronic lymphocytic leukemia (CLL), offering a simpler alternative to immunoglobulin heavy chain (IGVH) mutation status testing for patient prognosis.
Area of Science:
- Hematology
- Molecular Biology
- Oncology
Background:
- Immunoglobulin heavy chain variable region (IGVH) gene mutational status is a key prognostic indicator in B-cell chronic lymphocytic leukemia (CLL).
- Current IGVH mutation status determination is labor-intensive, necessitating the development of alternative prognostic markers for efficient CLL diagnostics.
Purpose of the Study:
- To identify and validate novel gene expression markers for predicting prognosis in CLL.
- To evaluate the utility of selected gene expression profiles as alternatives to IGVH mutational status for CLL diagnostics.
Main Methods:
- Ten candidate genes were selected based on differential expression in IGVH mutated versus unmutated CLL cases.
- Real-time quantitative polymerase chain reaction (RQ-PCR) was used to assess gene expression in 130 unpurified CLL patient samples.
- Gene expression levels were also determined in normal hematopoietic cells to control for contamination.
Main Results:
- Selected genes, including LPL, ZAP70, ADAM29, and SEPT10, demonstrated prognostic significance.
- Lipoprotein lipase (LPL) expression was identified as the strongest predictor of survival in CLL patients.
- LPL expression and IGVH mutational status showed comparable predictive value for survival, outperforming ZAP70 expression.
Conclusions:
- Lipoprotein lipase (LPL) gene expression serves as a reliable predictor of survival in CLL.
- LPL expression offers a more practical and equally effective prognostic tool compared to IGVH mutational status and ZAP70 in unpurified CLL samples.
Background And Objectives:
The mutational status of the immunoglobulin heavy chain variable region genes (IGVH) is a strong indicator of prognosis in B-cell chronic lymphocytic leukaemia (CLL). Since the determination of the IGVH mutation status is very labor-intensive, alternative prognostically relevant markers would facilitate CLL diagnostics.
Design And Methods:
Ten genes were selected from previously published gene expression profiling studies based on their differential expression in IGVH mutated versus unmutated cases of CLL, and tested with real-time quantitative polymerase chain reaction (RQ-PCR) in unpurified samples from 130 CLL patients. To ascertain potential contaminating effects by normal hematopoietic cells, the expression levels of the selected genes were determined in normal monocytes, B cells, T cells, NK cells and granulocytes.
Results:
The selected genes, i.e., ZAP70, LPL, SPG20, ADAM29, NRIP1, AKAP12, DMD, SEPT10, TPM2 and CLECSF2, showed prognostic significance. In multivariate logistic regression analysis expression levels of LPL, ZAP70, ADAM29 and SEPT10 were the most predictive for IGVH mutational status. In univariate analysis the expression of LPL was the best predictor. For survival, expression of LPL was the strongest prognostic factor. In combination with the three cytogenetic markers associated with a poor prognosis, i.e., deletions 17p13, 11q22 and trisomy 12, expression of LPL and IGVH mutational status performed equally well with regard to their predictive value for survival, both being more predictive than ZAP70.
Interpretation And Conclusions:
This study demonstrates that LPL expression is a predictor for survival in CLL, and for this purpose is as good as IGVH mutational status and more reliable than ZAP70 expression when tested in unpurified CLL samples.