Rombout Ans, Stamatopoulos Basile, Lagneaux Laurence, Lust Sofie, Offner Fritz, Naessens Evelien, Vanderstraeten Hanne, Verhasselt Bruno, Philippé Jan
Department of Clinical Chemistry, Microbiology and Immunology, Ghent University Hospital, Ghent University, Ghent, Belgium.
Laboratory of Clinical Therapy, Institut Jules Bordet, Université Libre de Bruxelles (ULB), Brussels, Belgium.
PLoS One. 2015 Mar 26;10(3):e0121526. doi: 10.1371/journal.pone.0121526. eCollection 2015.
Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world and is characterized by a heterogeneous clinical course. This variability in clinical course has spiked the search for prognostic markers able to predict patient evolution at the moment of diagnosis. Markers demonstrated to be of value are the mutation status of the immunoglobulin heavy chain variable region genes (IGHV) and lipoprotein lipase (LPL) expression. High LPL mRNA expression has been associated with short treatment free (TFS) and decreased overall survival (OS) in CLL. The LPL SNPs rs301 (T<C), rs328 (C<G) and rs13702 (T<C) have been associated with various metabolic disorders, but the association with CLL evolution is unknown. Here, in a cohort of 248 patients, we show that patients with the LPL SNP rs13702 wild-type T/T genotype had significantly shorter OS than patients with C/C and T/C genotypes (median time until CLL related death: 90 and 156 months respectively, p=0.008). The same was observed for LPL SNP rs301 (median time until CLL related death T/T: 102 and C/C, T/C: 144 months, p=0.03). Both SNPs rs301 and rs13702 were significantly associated with each other and notably, no association was found between IGHV status and presence of the SNP genotypes, indicating that these LPL SNPs are reliable prognostic markers that could add extra prognostic and predictive information to classical markers and help to improve the management of CLL.
慢性淋巴细胞白血病(CLL)是西方世界最常见的白血病,其临床病程具有异质性。临床病程的这种变异性激发了对能够在诊断时预测患者病情发展的预后标志物的探索。已证明具有价值的标志物是免疫球蛋白重链可变区基因(IGHV)的突变状态和脂蛋白脂肪酶(LPL)的表达。高LPL mRNA表达与CLL患者较短的无治疗生存期(TFS)和总生存期(OS)降低相关。LPL单核苷酸多态性(SNP)rs301(T<C)、rs328(C<G)和rs13702(T<C)与多种代谢紊乱相关,但与CLL病情发展的关联尚不清楚。在此,在一个248名患者的队列中,我们发现LPL SNP rs13702野生型T/T基因型的患者的OS明显短于C/C和T/C基因型的患者(直至CLL相关死亡的中位时间:分别为90个月和156个月,p=0.008)。LPL SNP rs301也观察到同样的情况(直至CLL相关死亡的中位时间T/T:102个月,C/C和T/C:144个月,p=0.03)。SNP rs301和rs13702彼此显著相关,值得注意的是,未发现IGHV状态与SNP基因型存在之间的关联,这表明这些LPL SNP是可靠的预后标志物,可以为经典标志物增添额外的预后和预测信息,并有助于改善CLL的管理。