Department of Pediatrics and Adolescent Medicine, University of Ulm, 89075 Ulm, Germany.
Cancer Cell. 2011 Feb 15;19(2):206-17. doi: 10.1016/j.ccr.2010.11.014. Epub 2011 Feb 3.
We investigated the engraftment properties and impact on patient outcome of 50 pediatric acute lymphoblastic leukemia (ALL) samples transplanted into NOD/SCID mice. Time to leukemia (TTL) was determined for each patient sample engrafted as weeks from transplant to overt leukemia. Short TTL was strongly associated with high risk for early relapse, identifying an independent prognostic factor. This high-risk phenotype is reflected by a gene signature that upon validation in an independent patient cohort (n = 197) identified a high-risk cluster of patients with early relapse. Furthermore, the signature points to independent pathways, including mTOR, involved in cell growth and apoptosis. The pathways identified can directly be targeted, thereby offering additional treatment approaches for these high-risk patients.
我们研究了 50 例小儿急性淋巴细胞白血病（ALL）样本移植到 NOD/SCID 小鼠中的植入特性及其对患者预后的影响。每个患者样本的白血病植入时间（TTL）定义为从移植到明显白血病的周数。TTL 短与早期复发的高风险密切相关，是一个独立的预后因素。该高危表型反映了一个基因特征，该特征在独立的患者队列（n=197）中得到验证，确定了一个具有早期复发的高危患者聚类。此外，该特征还指向独立的途径，包括 mTOR，这些途径涉及细胞生长和细胞凋亡。所确定的途径可以直接靶向，从而为这些高危患者提供额外的治疗方法。
