Riedt Tamara, Ebinger Martin, Salih Helmut R, Tomiuk Jürgen, Handgretinger Rupert, Kanz Lothar, Grünebach Frank, Lengerke Claudia
Department of Hematology/Oncology, University of Tuebingen Medical Center II, Tuebingen, Germany.
Blood. 2009 Apr 23;113(17):4049-51. doi: 10.1182/blood-2008-12-196634. Epub 2009 Feb 13.
Members of the caudal (cdx) family of homeobox proteins are essential regulators of embryonic blood development in zebrafish. Previously, we reported that the murine homologues (Cdx1, Cdx2, and Cdx4) affect formation and differentiation of embryonic stem cell (ESC)-derived hematopoietic progenitor cells. Consistent with the notion that embryonic pathways can reactivate during adult oncogenesis, recent studies suggest involvement of CDX2 in human acute myeloid leukemia (AML). Here we study CDX2 in healthy and leukemic human lymphoid cells, and show that a majority of leukemic samples display various degrees of aberrant CDX2 expression. Analysis of a cohort of 37 childhood acute lymphoblastic leukemia (ALL) patients treated in our hospital reveals that high CDX2 expression levels at diagnosis correlate with persistence of minimal residual disease (MRD) during the course of treatment. Thus, CDX2 expression levels may serve as a marker for adverse prognosis in pediatric ALL.
同源框蛋白尾型(cdx)家族成员是斑马鱼胚胎血液发育的重要调节因子。此前,我们报道过小鼠同源物(Cdx1、Cdx2和Cdx4)会影响胚胎干细胞(ESC)衍生的造血祖细胞的形成和分化。与胚胎途径可在成人肿瘤发生过程中重新激活这一观点一致,最近的研究表明CDX2参与人类急性髓系白血病(AML)。在此,我们研究健康和白血病人类淋巴细胞中的CDX2,并表明大多数白血病样本表现出不同程度的CDX2异常表达。对我院治疗的37例儿童急性淋巴细胞白血病(ALL)患者队列的分析显示,诊断时CDX2高表达水平与治疗过程中微小残留病(MRD)的持续存在相关。因此,CDX2表达水平可能作为儿童ALL不良预后的一个标志物。