cis-Retinoic acid stimulates the clonal growth of some myeloid leukemia cells in vitro.

cis-Retinoic acid stimulates the clonal growth of some myeloid leukemia cells in vitro.
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顺式视黄酸在体外刺激一些骨髓性白血病细胞的克隆生长。

DOI:
10.1182/blood.v69.1.302.302
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发表时间:
1987
期刊:
影响因子:
20.3
通讯作者:
G. Bagby
G. Bagby
中科院分区:
医学1区
文献类型:
--
作者:
H. J. Lawrence;K. Conner;M. Kelly;M. Haussler;P. Wallace;G. Bagby

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本文观察了顺式维甲酸(cisRA)对35例急性非淋巴细胞白血病(ANLL)白血病细胞集落形成的影响。我们观察到10(-7)至10(-6)M顺式RA对17个样本的白血病集落生长有显著抑制作用。然而,我们发现,类维生素A暴露导致显着刺激克隆生长在10个样品在相同的药物浓度。除了具有早幼粒细胞特征的病例外,没有形态学或功能证据表明cisRA诱导白血病母细胞分化。抑制和刺激都是剂量依赖性的,并且在可达到的cisRA水平下可观察到。具有单核细胞特征的白血病细胞比没有单核细胞特征的白血病细胞更频繁地表现出刺激性反应。T淋巴细胞和单核细胞的消耗并没有改变生长反应的类型。对五个样品(两个具有抑制性生长反应,两个具有刺激性反应,一个没有生长)进行细胞视黄酸结合蛋白(CRABP)测定,并且在任何情况下都没有发现可检测水平的CRABP。向白血病细胞的液体悬浮液中加入顺式RA,活细胞的数量没有显著变化。我们得出结论,顺式RA对白血病集落生长的影响是没有细胞毒性的,不介导的T淋巴细胞,单核细胞,或CRABP。更重要的是,cisRA似乎在体外增强某些人白血病细胞的生长。考虑到类维生素A在白血病患者临床试验中的使用越来越多,后一项发现可能是一个重要的警示。
We studied the effects of cis-retinoic acid (cisRA) on the clonogenic growth of samples of leukemic cells from 35 patients with acute nonlymphocytic leukemia (ANLL). We observed significant inhibition of leukemic colony growth in 17 samples by 10(-7) to 10(-6)M cisRA. However, we found that retinoid exposure resulted in striking stimulation of clonal growth in ten samples at the same drug concentrations. With the exception of cases with promyelocytic features, there was no morphologic or functional evidence that cisRA induced the leukemic blasts to differentiate. Both inhibition and stimulation were dose-dependent and observable at pharmacologically achievable levels of cisRA. Leukemic cells with monocytic features more frequently demonstrated a stimulatory response than did those without monocytic features. Depletion of T lymphocytes and monocytes did not alter the type of growth response. Assays for cellular retinoic acid-binding protein (CRABP) were performed on five samples (two with inhibitory growth responses, two with stimulatory responses, and one with no growth) and failed to reveal detectable levels of CRABP in any case. The addition of cisRA to liquid suspensions of leukemic cells produced no significant change in the number of viable cells. We conclude that the effects of cisRA on leukemic colony growth are not cytotoxic and not mediated by T lymphocytes, monocytes, or CRABP. More importantly, cisRA appears to enhance the growth of certain human leukemia cells in vitro. Taking into account the increasing use of retinoids in clinical trials for patients with leukemia, the latter findings may represent a significant cautionary note.
DOI: 10.1073/pnas.80.18.5525
发表时间: 1983-01-01
期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子: --
作者:
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发表时间: 1983
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DOI: --
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期刊: Cancer treatment reports
影响因子: --
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