Establishment of a retinoic acid-resistant human acute promyelocytic leukaemia (APL) model in human granulocyte-macrophage colony-stimulating factor (hGM-CSF) transgenic severe combined immunodeficiency (SCID) mice.
Establishment of a retinoic acid-resistant human acute promyelocytic leukaemia (APL) model in human granulocyte-macrophage colony-stimulating factor (hGM-CSF) transgenic severe combined immunodeficiency (SCID) mice.
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DOI：
10.1038/bjc.1998.596
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发表时间：
1998-10
影响因子：
8.8
通讯作者：
Ikeda Y
中科院分区：
文献类型：
--
作者：
Fukuchi Y;Kizaki M;Kinjo K;Awaya N;Muto A;Ito M;Kawai Y;Umezawa A;Hata J;Ueyama Y;Ikeda Y
为了了解机制并确定克服急性早幼粒细胞白血病（APL）中维甲酸（RA）耐药的新方法，我们在严重联合免疫缺陷（SCID）小鼠中建立了第一个人RA耐药APL模型。UF-1细胞是本实验室建立的RA耐药APL细胞系，将其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小鼠中没有形成。单细胞悬液（UF-1/GMTg SCID细胞）在形态学、免疫学、细胞遗传学和分子遗传学特征上与亲本UF-1细胞相似。全反式维甲酸不改变细胞的形态学特征或其CD 11b的表达。MTT法测定细胞生长曲线，表明UF-1/GMTg SCID细胞对RA具有抗性。这些结果表明，这是第一个RA耐药APL动物模型，可能是有用的，在体内研究这种骨髓性白血病的生物学，以及评估新的治疗方法，包括RA耐药APL患者。
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.