Estrov Z, Meir R, Barak Y, Zaizov R, Zadik Z
Efrati Institute for Blood Cell Research and Cytology, Department of Internal Medicine B, Israel.
J Clin Oncol. 1991 Mar;9(3):394-9. doi: 10.1200/JCO.1991.9.3.394.
As the number of long-term survivors of childhood leukemia increases, growth retardation has emerged as a significant complication. Treatment of these children with growth hormone (GH) has been suggested and sporadically implemented. We, therefore, studied the effect of human GH (hGH) and its by-product insulin-like growth factor-1 (IGF-1) on the growth of leukemic cells in vitro. Under serum-free conditions hGH and IGF-1 induced a significant dose-dependent proliferative effect on promyelocytic leukemia (HL60) and Burkitt's lymphoma (Daudi) cell lines. Anti-hGH antibodies negated the stimulatory effect of hGH and anti-IGF-1 serum abrogated the growth-promoting effect enhanced by IGF-1. Similar statistically significant stimulatory properties were found when freshly obtained marrow cells from four of five acute lymphoblastic leukemia (ALL) of childhood and four acute myelogenous leukemia (AML) patients were studied in ALL and AML blast-cell clonogenic assays. ALL colonies increased numerically by 72% (P less than .025) and AML colonies by 92% (P less than .01) in the presence of hGH at concentrations of 2.5 x 10(2) and 3.0 x 10(2) ng/mL, respectively. IGF-1 stimulated ALL and AML blast-colony growth at concentrations ranging from 0.05 to 0.5 ng/mL by up to 105% (P less than .025) and 65% (P less than .03), respectively. Our in vitro data suggest that circulating hGH and IGF-1 may promote leukemic blast cell replication in vivo, and the supplemental administration of hGH to leukemia patients in remission must be carefully monitored for early relapse.
随着儿童白血病长期存活者数量的增加,生长发育迟缓已成为一种重要的并发症。有人建议并偶尔实施用生长激素(GH)治疗这些儿童。因此,我们研究了人生长激素(hGH)及其副产品胰岛素样生长因子-1(IGF-1)对白血病细胞体外生长的影响。在无血清条件下,hGH和IGF-1对早幼粒细胞白血病(HL60)和伯基特淋巴瘤(Daudi)细胞系具有显著的剂量依赖性增殖作用。抗hGH抗体消除了hGH的刺激作用,抗IGF-1血清消除了IGF-1增强的促生长作用。在对五例儿童急性淋巴细胞白血病(ALL)中的四例和四例急性髓性白血病(AML)患者新鲜获取的骨髓细胞进行ALL和AML原始细胞克隆形成试验时,发现了类似的具有统计学意义的刺激特性。在浓度分别为2.5×10²和3.0×10² ng/mL的hGH存在下,ALL集落数量增加了72%(P<0.025),AML集落增加了92%(P<0.01)。IGF-1在0.05至0.5 ng/mL的浓度范围内刺激ALL和AML原始细胞集落生长,分别高达105%(P<0.025)和65%(P<0.03)。我们的体外数据表明,循环中的hGH和IGF-1可能在体内促进白血病原始细胞的复制,对于缓解期白血病患者补充hGH必须密切监测以防早期复发。