Chronic myelogenous leukemia: in vitro studies of hematopoietic regulation in a patient undergoing intensive chemotherapy.

Chronic myelogenous leukemia: in vitro studies of hematopoietic regulation in a patient undergoing intensive chemotherapy.
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慢性粒细胞白血病:接受强化化疗的患者造血调节的体外研究。

DOI:
10.1172/jci110193
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发表时间:
1981
期刊:
The Journal of clinical investigation
影响因子:
--
通讯作者:
Fialkow,PJ
Fialkow,PJ
中科院分区:
--
文献类型:
--
作者:
Singer,JW;Adamson,JW;Arlin,ZA;Kempin,SJ;Clarkson,BD;Fialkow,PJ

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1例X-连锁酶葡萄糖-6-磷酸脱氢酶杂合子伴费城染色体阳性慢性髓细胞性白血病(CML)患者接受联合化疗,经葡萄糖-6-磷酸脱氢酶测定,费城染色体部分缺失伴非克隆性造血部分恢复。化疗后进行体外造血研究,以评估肿瘤干细胞对正常细胞的影响,并确定白血病干细胞与正常干细胞之间是否存在物理和细胞动力学差异。结果表明:(1)正常定向粒细胞干细胞(CFU-C)和红系干细胞(BFU-E)在血液中的频率与骨髓中的频率没有差异。(b)发现正常的晚期红系祖细胞(CFU-E)的频率明显低于更原始的BFU-E。计算表明,不仅正常BFU-E产生的CFU-E减少,而且CML BFU-E的克隆扩增也异常(正常祖细胞的CFU-E:BFU-E比为1.1,而CML克隆的CFU-E:BFU-E比为11.5)。(c)骨髓细胞经高比活度氚标记胸苷照射后,正常CFU-C的频率未见增加。(d)正常CFU-C和CML克隆的CFU-C在密度的基础上是不可分离的。(e)正常BFU-E的频率始终大于CFU-C的频率,这表明调节差异影响正常祖细胞对这两种途径的承诺。
A patient heterozygous for the X-linked enzyme glucose-6-phosphate dehydrogenase and with Philadelphia chromosome-positive chronic myelogenous leukemia (CML) was treated with combination chemotherapy and had a partial loss of Philadelphia chromosome accompanied by partial restoration of nonclonal hematopoiesis as determined by glucose-6-phosphate dehydrogenase. Studies of in vitro hematopoiesis were performed after chemotherapy to evaluate the influences of neoplastic stem cells on normal cells and to determine whether there were physical and cell kinetic differences between leukemic stem cells and their normal counterparts. The data revealed the following: (a) The frequencies of normal committed granulocytic stem cells (CFU-C) and erythroid stem cells (BFU-E) in blood did not differ from the frequencies in marrow. (b) Normal late erythroid progenitors (CFU-E) were found at a significantly lower frequency that the more primitive BFU-E. Calculations indicated that not only was there a decrease in CFU-E production by normal BFU-E, but there was also abnormal clonal expansion of CML BFU-E (CFU-E:BFU-E ratio for normal progenitors was 1.1, whereas for the CML clone it was 11.5). (c) No increase in frequency of normal CFU-C was found after marrow cells were exposed to high specific activity tritiated thymidine. (d) Normal CFU-C and those from the CML clone were not separable on the basis of density. (e) The frequency of normal BFU-E was consistently greater than that of CFU-C, suggesting that regulatory differences influence the commitment of normal progenitors to the two pathways.