LPL is the strongest prognostic factor in a comparative analysis of RNA-based markers in early chronic lymphocytic leukemia

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BlankLPL is the strongest prognostic factor in a comparative analysis of

RNA-based markers in early chronic lymphocytic leukemia.

MA Kaderi, M Kanduri, AM Buhl, M Sevov, N Cahill, R Gunnarsson, M Jansson, K

Ekstrom Smedby, H Hjalgrim, J Jurlander, G Juliusson, L Mansouri, and R

Rosenquist

Haematologica, April 20, 2011; .

Genetics and Pathology, Uppsala University, Sweden;

Background. The expression levels of LPL, ZAP70, TCL1A, CLLU1 and MCL1 have

recently been proposed as prognostic factors in chronic lymphocytic leukemia.

However, few studies have systematically compared these different RNA-based

markers. Design and Methods. Using real-time quantitative PCR, we measured the

mRNA expression levels of these genes in unsorted samples from 252 newly

diagnosed chronic lymphocytic leukemia patients and correlated our data with

established prognostic markers (for example Binet stage, CD38, IGHV gene

mutational status and genomic aberrations) and clinical outcome. Results. High

expression levels of all RNA-based markers, except MCL1, predicted shorter

overall survival and time to treatment, with LPL being the most significant. In

multivariate analysis including the RNA-based markers, LPL expression was the

only independent prognostic marker for overall survival and time to treatment.

When studying LPL expression and the established markers, LPL expression

retained its independent prognostic strength for overall survival. All of the

RNA-based markers, albeit with varying ability, added prognostic information to

established markers, with LPL expression giving the most significant results.

Notably, high LPL expression predicted a worse outcome in good-prognosis

subgroups, such as patients with mutated IGHV genes, Binet stage A, CD38

negativity or favorable cytogenetics. In particular, the combination of LPL

expression and CD38 could further stratify Binet A patients. Conclusion. LPL

expression is the strongest RNA-based prognostic marker in chronic lymphocytic

leukemia that could potentially be applied to predict outcome in the clinical

setting, particularly in the large group of patients with favorable prognosis.

PMID: 21508119