Retinoic acid and granulocyte colony-stimulating factor synergistically induce leukocyte alkaline phosphatase in acute promyelocytic leukemia cells.
Retinoic acid and granulocyte colony-stimulating factor synergistically induce leukocyte alkaline phosphatase in acute promyelocytic leukemia cells.
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视黄酸和粒细胞集落刺激因子协同诱导急性早幼粒细胞白血病细胞中的白细胞碱性磷酸酶。
作者：
Maurizio Giannl;M. Terao;S. Zanotta;T. Barbui;A. Rambaldi;E. Garattini
在这份报告中，我们显示了一个强大的协同相互作用粒细胞集落刺激因子（G-CSF）和全反式维甲酸（ATRA）的白细胞碱性磷酸酶（ALP）的表达在新鲜分离的急性早幼粒细胞白血病（APL）的原始细胞，以及在NB 40和HL-60细胞系。在这些细胞类型中观察到的强协同作用在两种急性白血病细胞系（K562和GF-D8）、正常粒细胞和单核细胞中不明显。在来自慢性粒细胞白血病（CML）的新鲜分离的白细胞中，在疾病的稳定期，ATRA和G-CSF之间的相互作用较弱。在NB 4中详细研究了细胞因子和类维生素A之间的相互作用，NB 4是一种永生化的APL白血病细胞系，保留了涉及视黄酸受体α型的15-17染色体易位。单独用G-CSF或单独用ATRA处理NB 4细胞分别不导致抗肿瘤活性的增加和轻微诱导。如果同时用两种化合物处理细胞，4天后观察到显著升高。当维甲酸浓度在10（-7）和10（-5）mol/L之间，细胞因子浓度在1和10 ng/mL之间时，G-CSF和ATRA之间的协同作用是明显的。两种化合物的同时存在对于获得最大的抗肿瘤活性增加是必要的，并且效果是细胞密度依赖性的。协同作用对G-CSF是特异性的，并且未观察到与其它细胞因子和粒细胞的功能诱导剂的协同作用。如通过使用特异性cDNA探针的北方印迹和核连续分析所确定的，增强的α-淀粉酶活性是肝/骨/肾型（L/B/K型）碱性磷酸酶基因的转录速率增加的结果。在用G-CSF和ATRA刺激后，在NB 4细胞中仅检测到L/B/K型碱性磷酸酶转录本的两种可能的选择性剪接形式中的一种。这种mRNA形式是在正常多形核白细胞中观察到的，含有最上游的前导外显子。在NB 4细胞中，ATRA诱导G-CSF、α和β维甲酸受体转录物，而G-CSF对这些mRNA的表达影响较小。
In this report we show a strong synergistic interaction between granulocyte colony-stimulating factor (G-CSF) and all-trans retinoic acid (ATRA) on the expression of leukocyte alkaline phosphatase (LAP) in freshly isolated acute promyelocytic leukemia (APL) blasts as well as in NB40 and HL-60 cell lines. The strong synergism observed in these cell types was not evident in two acute leukemia cell lines (K562 and GF-D8), in normal granulocytes, and in monocytes. In freshly isolated leukocytes derived from chronic myelogenous leukemia (CML), in the stable phase of the disease, a weaker interaction between ATRA and G-CSF was documented. The cross-talk between the cytokine and the retinoid was studied in detail in NB4, an immortalized APL leukemia cell line, retaining the 15-17 chromosomal translocation involving the retinoic acid receptor type alpha. The treatment of NB4 cells with G-CSF alone or ATRA alone leads to no increase and to minor induction in LAP activity, respectively. If the cells are treated with the two compounds simultaneously, a dramatic elevation of LAP is observed after 4 days. The synergism between G-CSF and ATRA is evident at concentrations of the retinoid between 10(-7) and 10(-5) mol/L and at concentrations of the cytokine between 1 and 10 ng/mL. The simultaneous presence of the two compounds is necessary to obtain maximal increase of LAP activity and the effect is cell density-dependent. Synergism is specific for G-CSF, and it is not observed with other cytokines and functional inducers of the granulocyte. The augmentation of LAP activity is the consequence of an increased transcriptional rate of the liver/bone/kidney-type (L/B/K-type) alkaline phosphatase gene, as determined by Northern blotting and nuclear run-on analysis using specific cDNA probes. Only one of the two possible alternatively spliced forms of L/B/K-type alkaline phosphatase transcript is detected in NB4 cells after stimulation with G-CSF and ATRA. This mRNA form, which is the one observed in normal polymorphonuclear leukocytes, contains the most upstream leader exon. In NB4 cells, ATRA induces G-CSF, alpha, and beta retinoic acid receptor transcripts, whereas G-CSF has minor effects on the expression of these mRNAs.
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影响因子：
20.3
作者：
A. Rambaldi;D. Young;James D. Griffin
通讯作者：
A. Rambaldi;D. Young;James D. Griffin
编码小鼠胎盘碱性磷酸酶的 cDNA 的克隆和表征。
DOI：
10.1073/pnas.84.20.7051
发表时间：
1987
影响因子：
11.1
作者：
Terao,M;Mintz,B
通讯作者：
Mintz,B
影响因子：
5.9
作者：
LARSON, RA;KONDO, K;ROWLEY, JD
通讯作者：
ROWLEY, JD
影响因子：
158.5
作者：
WARRELL, RP;FRANKEL, SR;DMITROVSKY, E
通讯作者：
DMITROVSKY, E