急性白血病患者血清对正常红系造血抑制活性的研究

Study on the inhibitory activities of serum of acute leukemia patients to normal erythroid progenitor cells in vitro

目的:研究急性白血病(AL)患者血清在体外对正常红系造血祖细胞的抑制活性和产生该抑制活性的机制以及与患者贫血的关系。方法:采用体外半固体祖细胞集落培养技术检测初治AL患者81例和正常对照组40名的血清对正常人骨髓BFU鄄E和CFU鄄E增殖的影响;用ELISA法检测AL患者血清肿瘤坏死因子α(TNF鄄α)及γ干扰素;RT鄄PCR检测TNF鄄αmRNA。结果:AL患者血清对BFU鄄E和CFU鄄E的抑制率分别为(22.69±29.25)%、(17.71±24.31)%,均高于对照组,而急性髓细胞白血病(AML)和急性淋巴细胞白血病(ALL)患者之间无显著差异;AL患者血清对BFU鄄E和CFU鄄E的抑制率与患者血红蛋白负相关(r=-0.336、-0.328,P<0.01);AL患者血清TNF鄄α测定值为(904.20±1780.49)pg/ml,高于正常人,AL患者血清TNF鄄α水平与其血清对BFU鄄E和CFU鄄E的抑制率成正相关;5例AL患者白血病细胞TNF鄄αmRNA检测为阳性。结论:AL患者血清存在对正常红系造血祖细胞的抑制活性,且与患者的贫血相关。AL患者TNF鄄α增高,与该抑制活性有关,白血病细胞可分泌TNF鄄α,可能是患者血清TNF鄄α增高的原因之一。

Objective To investigate the inhibitory activities in vitro of serum of acute leukemia (AL) patients to the normal erythroid progenitor cells, and to clarify the relation between the anemia and the inhibitory activities. Metho-ds Semi-solid culture in vitro, ELISA and RT-PCR were used in this study. Eighty one novel patients with AL and 40 healthy volunteers as controls were involved. Results The inhibitory rates(IR) to the growth of BFU-E and CFU-E from normal bone marrow of the serum in the patients with AL were (22.69±29.25)% and (17.71±24.31)%,respectively, both of which were significantly higher than those in controls. There was no significant difference between the inhibitory rates in patients with acute lymphocytic leukemia (ALL) and those in patients with acute non-lymphocytic leukemia (ANLL). The serum IR to the growth of BFU-E and CFU-E in the patients with AL were reversely correlated to the hemoglobin value (r=-0.336 and -0.328) respectively(P<0.01). The serum TNF-α level [(904.20±1780.49) pg/ml] in the AL patients was significantly higher than that in controls. The TNF-α level in the AL patients was positively correlated to the serum IR to BFU-E and CFU-E. The TNF-α mRNA expressions in the leukemic cells from 5 AL patients were positive. Conclusions The inhibitory activities to the normal erythroid progenitor cells exist in the serum of the AL patients, which may cause anemia. The increased serum TNF-α levels in the AL patients may play a major role in the occurrence of anemia. The leukemic cells can secrete TNF-α, which may induced the elevation of the serum TNF-α level in the AL patients.