Schmetzer H M, Gerhartz H H, Wilmanns W
Klinikum Grosshadern, Third Department of Medicine, University of Munich, Marchioninistrasse 15, D-81377 Munich, Germany.
Ann Hematol. 1999 Oct;78(10):449-55. doi: 10.1007/s002770050597.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is known to stimulate granulocytes, monocytes, and macrophages. We studied the effect of GM-CSF on (clonal) bone marrow (BM) cells obtained from AML patients after 7 days of culture in vitro: BM samples were obtained from 19 AML patients at diagnosis (DIA), from two patients with persisting disease (PERS), from eight patients in complete remission (CR), and from 12 healthy donors. Flow-cytometric comparison of differentiated, CD 15-positive cells or of CD34-positive blast cells before and after cultivation showed that the proportion of CD15-positive cells was increased in nine of 12 healthy BM samples, in 14 of 19 cases at DIA, in one of three cases during PERS, and in five of six cases in CR of AML. The proportion of CD34-positive cells was increased in one of 12 healthy BM samples, in seven of 19 cases at DIA, in one of two cases during PERS, and in three of seven cases in CR of AML. Southern blot analysis (SBA) performed in six cases during the course of AML, before and after cell culture, showed that clonal DNA increased after GM-CSF treatment in three of five cases studied at DIA, in six of nine cases studied in CR, in the one case studied at PERS, and in the one studied at relapse (REL). In one case of trisomy 8 at DIA a normal karyotype was demonstrated in CR. However, after 7 days of cultivation of the cells in GM-CSF the trisomy 8 was detected in two of 17 metaphases isolated from colony-cells from methylcellulose cultures. Our data show that a 7-day treatment of BM cells with GM-CSF induced a differentiation of healthy and leukemic BM cells in the great majority of cases. An enrichment of CD34-positive cells was not achieved in healthy BM samples. However, in 70% of the cases in CR and in 30% of the cases at DIA of AML, clonal CD34-positive cells were enriched. This means that GM-CSF stimulates ('primes') leukemic cell growth in vitro.
已知粒细胞-巨噬细胞集落刺激因子（GM-CSF）可刺激粒细胞、单核细胞和巨噬细胞。我们研究了GM-CSF对急性髓系白血病（AML）患者体外培养7天后获得的（克隆性）骨髓（BM）细胞的影响：BM样本取自19例AML患者诊断时（DIA）、2例持续性疾病患者（PERS）、8例完全缓解患者（CR）以及12名健康供者。对培养前后分化的CD15阳性细胞或CD34阳性原始细胞进行流式细胞术比较，结果显示，12份健康BM样本中的9份、DIA时19例中的14例、PERS时3例中的1例以及AML缓解期6例中的5例，CD15阳性细胞比例增加。12份健康BM样本中的1份、DIA时19例中的7例、PERS时2例中的1例以及AML缓解期7例中的3例，CD34阳性细胞比例增加。在AML病程中的6例患者细胞培养前后进行的Southern印迹分析（SBA）显示，DIA时研究的5例中有3例、CR时研究的9例中有6例、PERS时研究的1例以及复发时（REL）研究的1例，GM-CSF处理后克隆性DNA增加。1例DIA时8号三体患者在CR时显示核型正常。然而，在GM-CSF中培养细胞7天后，从甲基纤维素培养物的集落细胞中分离的17个中期细胞中有2个检测到8号三体。我们的数据表明，在大多数情况下，用GM-CSF对BM细胞进行7天治疗可诱导健康和白血病BM细胞分化。健康BM样本中未实现CD34阳性细胞富集。然而，在AML缓解期70%的病例和DIA时30%的病例中，克隆性CD34阳性细胞富集。这意味着GM-CSF在体外刺激（“启动”）白血病细胞生长。
