Fukuchi Y, Kizaki M, Kinjo K, Awaya N, Muto A, Ito M, Kawai Y, Umezawa A, Hata J, Ueyama Y, Ikeda Y
Hu-Mouse Project, Eighth Laboratory, Kanagawa Academy of Science and Technology, Japan.
Br J Cancer. 1998 Oct;78(7):878-84. doi: 10.1038/bjc.1998.596.
To understand the mechanisms and identify novel approaches to overcoming retinoic acid (RA) resistance in acute promyelocytic leukaemia (APL), we established the first human RA-resistant APL model in severe combined immunodeficiency (SCID) mice. UF-1 cells, an RA-resistant APL cell line established in our laboratory, were transplanted into human granulocyte-macrophage colony-stimulating factor (GM-CSF)-producing SCID (hGMTg SCID) mice and inoculated cells formed subcutaneous tumours in all hGMTg SCID mice, but not in the non-transgenic control SCID mice. Single-cell suspensions (UF-1/GMTg SCID cells) were similar in morphological, immunological, cytogenetic and molecular genetic features to parental UF-1 cells. All-trans RA did not change the morphological features of cells or their expression of CD11b. RA did not alter the growth curve of cells as determined by MTT assay, suggesting that UF-1/GMTg SCID cells are resistant to RA. These results demonstrate that this is the first RA-resistant APL animal model that may be useful for investigating the biology of this myeloid leukaemia in vivo, as well as for evaluating novel therapeutic approaches including patients with RA-resistant APL.
为了解急性早幼粒细胞白血病（APL）中维甲酸（RA）耐药的机制并确定克服耐药的新方法，我们在严重联合免疫缺陷（SCID）小鼠中建立了首个人类RA耐药APL模型。将我们实验室建立的RA耐药APL细胞系UF-1细胞移植到产生人粒细胞-巨噬细胞集落刺激因子（GM-CSF）的SCID（hGMTg SCID）小鼠中，接种的细胞在所有hGMTg SCID小鼠中形成皮下肿瘤，但在非转基因对照SCID小鼠中未形成。单细胞悬液（UF-1/GMTg SCID细胞）在形态、免疫、细胞遗传学和分子遗传学特征上与亲本UF-1细胞相似。全反式维甲酸（ATRA）未改变细胞的形态特征或其CD11b的表达。通过MTT法测定，维甲酸未改变细胞的生长曲线，表明UF-1/GMTg SCID细胞对维甲酸耐药。这些结果表明，这是首个RA耐药APL动物模型，可能有助于在体内研究这种髓系白血病的生物学特性，以及评估包括RA耐药APL患者在内的新治疗方法。
