Pisani F, Del Poeta G, Aronica G, Venditti A, Caravita T, Amadori S
Department of Hematology, University Tor Vergata, St. Eugenio Hospital, Rome, Italy.
Ann Hematol. 1997 Oct;75(4):145-7. doi: 10.1007/s002770050332.
Using flow cytometry, we have investigated the effects of 0.5 microM all-trans-retinoic acid (ATRA) on bcl-2 expression in the blast cells of 25 acute myeloblastic leukemia (AML) patients and the HL-60 cell line after incubation for 6 days. We observed a significant decrease of bcl-2 expression after treatment with ATRA in 12 of 25 AML samples and the HL-60 cells. The mean fluorescence intensity (MFI) ratio for the bcl-2 levels of the ATRA responders (n = 12) was reduced to 7.9 +/- 4.8 following incubation with ATRA compared with 10.9 +/- 6.5 (mean +/- SD) for control samples incubated without ATRA (p = 0.011). There was no significant difference between the baseline bcl-2 MFI ratio in the ATRA responders (11.14 +/- 7, n = 12) and the non responders (14.18 +/- 11.3, n = 13; p = 0.432). The down-regulation of bcl-2 expression by ATRA was not significantly associated with CD34-negative or -positive AML. There was no correlation between AML subtypes and regulation of bcl-2 expression by ATRA. Complete remission and overall survival were not significantly improved in bcl-2 down-regulated cases. Our data confirm that ATRA can down-regulate the bcl-2 expression in AML blasts. Because many chemotherapeutic agents also operate through the activation of programmed cell death and bcl-2 levels are positively associated with resistance to apoptosis, ATRA can be used in combination chemotherapy to increase the chemosensitivity of some patients with AML.
我们运用流式细胞术，研究了0.5微摩尔全反式维甲酸（ATRA）对25例急性髓细胞白血病（AML）患者原始细胞及HL-60细胞系中bcl-2表达的影响，孵育6天后进行观察。我们发现，25例AML样本中的12例以及HL-60细胞在用ATRA处理后，bcl-2表达显著下降。与未用ATRA孵育的对照样本（平均荧光强度[MFI]比值为10.9±6.5）相比，ATRA反应者（n = 12）在用ATRA孵育后，其bcl-2水平的MFI比值降至7.9±4.8（p = 0.011）。ATRA反应者（11.14±7，n = 12）和非反应者（14.18±11.3，n = 13；p = 0.432）的基线bcl-2 MFI比值无显著差异。ATRA对bcl-2表达的下调与CD34阴性或阳性AML无显著相关性。AML亚型与ATRA对bcl-2表达的调节之间无相关性。在bcl-2下调的病例中，完全缓解率和总生存率未得到显著改善。我们的数据证实，ATRA可下调AML原始细胞中的bcl-2表达。由于许多化疗药物也通过激活程序性细胞死亡发挥作用，且bcl-2水平与细胞凋亡抗性呈正相关，因此ATRA可用于联合化疗，以提高部分AML患者的化疗敏感性。
