Lipoprotein lipase mRNA expression in whole blood is a prognostic marker in B cell chronic lymphocytic leukemia.
BACKGROUND
Chronic lymphocytic leukemia (CLL) is characterized by high individual variability in clinical course and the need for therapy. Differentiation of prognostic subgroups is based primarily on the mutation status of the genes for the variable region of the immunoglobulin heavy chain (IGHV). The time- and labor-intensive nature of this analysis necessitates the use of easily applicable surrogate markers.


METHODS
We developed a quantitative PCR (qPCR) method for determining lipoprotein lipase (LPL) mRNA expression and analyzed samples of lysed whole blood and CD19-selected cells from 50 CLL patients. Associations of LPL and ZAP70 [zeta-chain (TCR) associated protein kinase 70 kDa] expression with IGHV mutation status, overall survival (OS), and treatment-free survival (TFS) were investigated.


RESULTS
Lysed samples of whole blood and CD19-selected cells were similar with respect to LPL expression (R = 0.88; P <0.0001). LPL expression was significantly associated with IGHV mutation status [chi(2)(1) = 15.3; P <0.0001] and showed an 89.3% specificity, a 68.2% sensitivity, an 83.3% positive predictive value, and a 78.1% negative predictive value for IGHV mutation status. LPL expression was significantly associated with both OS and TFS in log-rank tests (both P values = 0.002). LPL-positive patients had a significantly shorter median TFS time (23 months) than LPL-negative patients (88 months) (P = 0.002).


CONCLUSIONS
LPL mRNA expression is a valuable prognostic marker in CLL. The method does not require cell purification, and its applicability with archived samples facilitates its use in the clinical routine and other studies.
Van Bockstaele
Femke
F
Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent, Belgium.
Pede
Valerie
V
Janssens
Ann
A
Callewaert
Filip
F
Offner
Fritz
F
Verhasselt
Bruno
B
Philippé
Jan
J
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D005260:Female; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000175:diagnosis*; D008071:Lipoprotein Lipase / Q000097:blood* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011379:Prognosis; D012333:RNA, Messenger / Q000097:blood* / Q000235:genetics; D016019:Survival Analysis; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000097:blood
D014408:Biomarkers, Tumor; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D012333:RNA, Messenger; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; D008071:Lipoprotein Lipase