Fan D, Zhou X, Li Z, Li Z-Q, Duan C, Liu T, Zhang F, Huang Y, Zhang Y, Gao F, Guo Y, Gupta R, Chen G, Enver T, Tang J, Hong D
Key Laboratory of Pediatric Hematology & Oncology Ministry of Health, Department of Pediatric Hematology and Oncology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, China.
Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Department of Pathophysiology, SJTU-SM, Shanghai, China.
Oncogene. 2015 Apr 16;34(16):2083-93. doi: 10.1038/onc.2014.148. Epub 2014 Jun 9.
Leukemic lymphoblasts within different immunophenotypic populations possess stem cell properties. However, whether or not the self-renewal program is retained from stem cells or conferred on progenitors by leukemogenic molecules remains unknown. We have addressed the issue in the context of TEL-AML1-associated acute lymphoblastic leukemia (ALL) by profiling a refined program edited from genes essential for self-renewal of hematopoietic stem cells and B-cell development. Bioinformatic analysis shows that ALL populations are loosely clustered and close to the normal population that contains stem and primitive progenitor cells. This finding indicates that immunophenotypes do not reflect maturation stages in ALL and that the self-renewal program may be retained from stem cells. Results of assessing 'first hit' function of TEL-AML1 in different populations of normal cells demonstrate the molecular model. Therefore, the current study shows a leukemogenic scenario of human ALL in which programs of stem cells are sustained in distinct fractions by leukemogenic mutations.
不同免疫表型群体中的白血病淋巴母细胞具有干细胞特性。然而，自我更新程序是从干细胞保留而来还是由致白血病分子赋予祖细胞，这一点仍然未知。我们通过对造血干细胞自我更新和B细胞发育所必需基因编辑的精细程序进行分析，在TEL-AML1相关急性淋巴细胞白血病（ALL）的背景下解决了这个问题。生物信息学分析表明，ALL群体松散聚集，且接近包含干细胞和原始祖细胞的正常群体。这一发现表明，免疫表型并不反映ALL中的成熟阶段，并且自我更新程序可能从干细胞保留而来。评估TEL-AML1在不同正常细胞群体中的“首次打击”功能的结果证明了该分子模型。因此，当前研究显示了人类ALL的一种致白血病情况，即干细胞程序通过致白血病突变在不同部分得以维持。
