Einat M, Lishner M, Amiel A, Nagler A, Yarkorli S, Rudi A, Kashman Y, Markel D, Fabian I
Department of Cell Biology and Histology, Sackler School of Medicine, Tel Aviv University, Israel.
Exp Hematol. 1995 Dec;23(14):1439-44.
We examined the effect of Eilatin, a novel marine product, on the survival of human myeloid progenitor cells (CFU-C) isolated from normal individuals and from 12 patients with Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) in chronic phase and blastic crisis. We compared its effect to the effect of interferon-alpha (IFN-alpha) and cytosine arabinoside (Ara-C). Eilatin, IFN-alpha, and Ara-C inhibited the proliferation of CFU-C from normal individuals and CML patients in a dose-dependent manner. The percent survival of colony-forming units from bone marrow (BM) of seven CML patients in chronic phase exposed for 16 hours to Eilatin (10(-7) and 10(-6) M), IFN-alpha (500 U/mL), or Ara-C (10(-9) M and 10(-8) M) was found to be statistically lower (p < 0.05) than the percent survival of myeloid progenitors from normal individuals. A 16-hour exposure of CD34+ cells isolated from peripheral blood (PB) of three CML patients in blastic crisis and from BM of two patients in chronic phase to Eilatin 10(-7) M, IFN-alpha 500 U/mL, Ara-C 10(-9) M resulted in a marked inhibition in the ability of the cells to proliferate in liquid culture and a reduction in CFU-C content. Using fluorescent in situ hybridization (FISH), we evaluated detection of the BCR/ABL fusion product in the CD34+ cells. All five patients were 100% Ph+ at diagnosis. BCR/ABL translocations were detected in 94.6 +/- 0.6% of CD34+ cells after growth in liquid culture for 7 days. The level of BCR/ABL fusion signals detected after exposure of CD34+ cells for 16 hours to Eilatin 10(-7) M, IFN-alpha 500 U/mL, or Ara-C 10(-9) M were 54.5 +/- 5%, 63.6 +/- 5%, and 70 +/- 4%, respectively (mean +/- SE, n = 5). Our data indicate that Eilatin, a substance isolated from the Red Sea purple tunicate Eudistoma sp., has an antileukemic effect against in vitro Ph+ cells and may be used in conjunction with currently available agents for ex vivo purging of BM and/or PB of CML patients in conjunction with autologous bone marrow transplantation.
我们研究了一种新型海洋产物Eilatin对从正常个体以及12例处于慢性期和急变期的费城染色体阳性（Ph+）慢性粒细胞白血病（CML）患者中分离出的人髓系祖细胞（CFU-C）存活的影响。我们将其效果与α干扰素（IFN-α）和阿糖胞苷（Ara-C）的效果进行了比较。Eilatin、IFN-α和Ara-C均以剂量依赖性方式抑制正常个体和CML患者的CFU-C增殖。发现7例处于慢性期的CML患者的骨髓（BM）中集落形成单位在暴露于Eilatin（10⁻⁷和10⁻⁶ M）、IFN-α（500 U/mL）或Ara-C（10⁻⁹ M和10⁻⁸ M）16小时后的存活百分比在统计学上低于正常个体髓系祖细胞的存活百分比（p < 0.05）。将3例处于急变期的CML患者外周血（PB）和2例处于慢性期患者的BM中分离出的CD34⁺细胞暴露于Eilatin 10⁻⁷ M、IFN-α 500 U/mL、Ara-C 10⁻⁹ M 16小时，导致细胞在液体培养中的增殖能力受到显著抑制，CFU-C含量降低。使用荧光原位杂交（FISH），我们评估了CD34⁺细胞中BCR/ABL融合产物的检测情况。所有5例患者在诊断时均为100% Ph+。在液体培养7天后，94.6±0.6%的CD34⁺细胞中检测到BCR/ABL易位。将CD34⁺细胞暴露于Eilatin 10⁻⁷ M、IFN-α 500 U/mL或Ara-C 10⁻⁹ M 16小时后检测到的BCR/ABL融合信号水平分别为54.5±5%、63.6±5%和70±4%（平均值±标准误，n = 5）。我们的数据表明，从红海紫色被囊动物Eudistoma sp.中分离出的物质Eilatin对体外Ph+细胞具有抗白血病作用，可与现有药物联合用于体外清除CML患者的BM和/或PB，用于自体骨髓移植。
