Results of MDR-1 vector modification trial indicate that granulocyte/macrophage colony-forming unit cells do not contribute to posttransplant hematopoietic recovery following intensive systemic therapy.
Results of MDR-1 vector modification trial indicate that granulocyte/macrophage colony-forming unit cells do not contribute to posttransplant hematopoietic recovery following intensive systemic therapy.
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MDR-1载体修饰试验的结果表明，粒细胞/巨噬细胞集落形成单位细胞对强化全身治疗后移植后造血恢复没有贡献。
DOI：
10.1073/pnas.93.26.15346
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发表时间：
1996
影响因子：
11.1
通讯作者：
中科院分区：
文献类型：
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作者：
Hanania,EG;Giles,RE;Kavanagh,J;Fu,SQ;Ellerson,D;Zu,Z;Wang,T;Su,Y;Kudelka,A;Rahman,Z;Holmes,F;Hortobagyi,G;Claxton,D;Bachier,C;Thall,P;Cheng,S;Hester,J;Ostrove,JM;Bird,RE;Chang,A;Korbling,M;Seong,D;Cote,R;
为了正式检验粒细胞/巨噬细胞集落形成单位（GM-CFU）细胞可有助于移植后立即早期造血重建的假设，通过定量原位聚合酶链反应（PCR）测量逆转录病毒载体转导后遗传修饰的GM-CFU的频率，所述PCR对多药耐药-1（MDR-1）载体具有特异性，和通过定量GM-CFU甲基纤维素平板测定。该分析的结果显示两种不同转导方案的产物中的转导频率之间没有差异：“悬浮转导”和“基质生长因子转导”。然而，当对移植后逆转录病毒MDR-1载体阳性细胞的频率进行分析时，10名移植了通过悬浮法转导的细胞的患者中0名在移植后对载体MDR-1呈阳性，而8例移植了通过基质生长因子方法转导的细胞的患者中有5例是MDR阳性的，1个载体转录单位（Fisher精确检验，P = 0.0065水平差异显著）。这些数据表明，只有非常小的骨髓细胞的GM-CFU部分的子集，如果有的话，有助于造血组织的再增殖，发生在强化全身治疗和自体造血细胞移植。
To formally test the hypothesis that the granulocyte/macrophage colony-forming unit (GM-CFU) cells can contribute to early hematopoietic reconstitution immediately after transplant, the frequency of genetically modified GM-CFU after retroviral vector transduction was measured by a quantitativein situpolymerase chain reaction (PCR), which is specific for the multidrug resistance-1 (MDR-1) vector, and by a quantitative GM-CFU methylcellulose plating assay. The results of this analysis showed no difference between the transduction frequency in the products of two different transduction protocols: “suspension transduction” and “stromal growth factor transduction.” However, when an analysis of the frequency of cells positive for the retroviral MDR-1 vector posttransplantation was carried out, 0 of 10 patients transplanted with cells transduced by the suspension method were positive for the vector MDR-1 posttransplant, whereas 5 of 8 patients transplanted with the cells transduced by the stromal growth factor method were positive for the MDR-1 vector transcription unit byin situor in solution PCR assay (a difference that is significant at theP= 0.0065 level by the Fisher exact test). These data suggest that only very small subsets of the GM-CFU fraction of myeloid cells, if any, contribute to the repopulation of the hematopoietic tissues that occurs following intensive systemic therapy and transplantation of autologous hematopoietic cells.