Hawley R G, Fong A Z, Lu M, Hawley T S
Division of Cancer Research, Sunnybrook Health Science Centre, Ontario, Canada.
Oncogene. 1994 Jan;9(1):1-12.
The t(10;14) chromosomal translocation of T-cell acute lymphoblastic leukemia joins the T-cell receptor delta gene to a region upstream of a diverged homeobox-containing gene called HOX11. To better understand the pathogenetic role of HOX11 in leukemogenesis, post 5-fluorouracil-treated murine bone marrow cells were infected with a replication-defective retrovirus bearing the gene. Constitutive expression of HOX11 in hematopoietic precursors yielded cell lines at high frequency consisting of immature cells belonging to the myeloid lineage. HOX11-transformed cell lines displayed a strict dependence on IL-3 for their survival and proliferation in culture and were not leukemogenic. The results support the hypothesis that the transforming capacity of HOX11 derives from its ability to alter the expression of genes regulating hematopoietic differentiation and that secondary mutations promoting cell survival or stimulating proliferation are required for progression to malignancy. The findings further suggest that the oncogenic activity of HOX11 might not be restricted to T-cell leukemias in humans.
T细胞急性淋巴细胞白血病的t(10;14)染色体易位将T细胞受体δ基因与一个名为HOX11的、含有同源异型框的分化基因上游区域连接起来。为了更好地理解HOX11在白血病发生中的致病作用，用携带该基因的复制缺陷型逆转录病毒感染经5-氟尿嘧啶处理的小鼠骨髓细胞。HOX11在造血前体细胞中的组成性表达高频产生由属于髓系谱系的未成熟细胞组成的细胞系。HOX11转化的细胞系在培养中其存活和增殖严格依赖IL-3，且不具有致白血病性。这些结果支持以下假说：HOX11的转化能力源于其改变调节造血分化基因表达的能力，并且进展为恶性肿瘤需要促进细胞存活或刺激增殖的二次突变。这些发现进一步表明，HOX11的致癌活性可能不限于人类T细胞白血病。
