van Grotel Martine, van den Heuvel-Eibrink Marry M, van Wering Elisabeth R, van Noesel Max M, Kamps Willem A, Veerman Anjo J P, Pieters Rob, Meijerink Jules P P
Department of Pediatric Oncology/Hematology, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands.
Pediatr Blood Cancer. 2008 Dec;51(6):737-40. doi: 10.1002/pbc.21707.
Children with T-lineage acute lymphoblastic leukemia (T-ALL) have an inferior outcome with combination chemotherapy compared to B-lineage ALL, and still about 30% of the patients relapse within the first 2 years following diagnosis. As CD34 has been related with poor outcome in ALL in general, we investigated the prognostic significance of the stem cell marker CD34, as well as the association of CD34 positivity with the expression of several multidrug resistance (MDR) genes.
In this retrospective study, we investigated the prognostic significance of the expression of the early T-cell differentiation marker CD34 and the expression of MDR genes in relation to outcome in a cohort of 72 newly diagnosed pediatric T-ALL patients.
CD34 expression was related to a poor 5-year disease-free-survival and a poor 5-year overall survival. Using the Cox proportional hazard model, CD34 expression predicted for increased risk for relapse and death. Expression of CD34 was associated with elevated MDR1 and MRP1 mRNA expression levels. For the entire T-ALL cohort, these expression levels of MDR1 or MRP1 did not independently predict for poor outcome.
We conclude that CD34-positive T-ALL has a relatively poor survival that is not explained by the mRNA expression levels of MDR1, LRP, or MRP1.
与B系急性淋巴细胞白血病(B-ALL)相比,T系急性淋巴细胞白血病(T-ALL)患儿接受联合化疗的预后较差,仍有大约30%的患者在诊断后的头2年内复发。由于CD34总体上与ALL的不良预后相关,我们研究了干细胞标志物CD34的预后意义,以及CD34阳性与几种多药耐药(MDR)基因表达的相关性。
在这项回顾性研究中,我们调查了72例新诊断的儿童T-ALL患者队列中早期T细胞分化标志物CD34的表达及MDR基因表达与预后的相关性。
CD34表达与5年无病生存率低及5年总生存率低相关。使用Cox比例风险模型,CD34表达预示复发和死亡风险增加。CD34表达与MDR1和MRP1 mRNA表达水平升高相关。对于整个T-ALL队列,MDR1或MRP1的这些表达水平并不能独立预测不良预后。
我们得出结论,CD34阳性的T-ALL生存率相对较差,这不能用MDR1、LRP或MRP1的mRNA表达水平来解释。