Bernstein I D, Singer J W, Smith F O, Andrews R G, Flowers D A, Petersens J, Steinmann L, Najfeld V, Savage D, Fruchtman S
Fred Hutchinson Cancer Research Center, Veterans Administration Medical Center, Seattle, WA 98104.
Blood. 1992 Apr 1;79(7):1811-6.
Acute myelogenous leukemia (AML) is a clonal disease that is heterogeneous with respect to the pattern of differentiative expression of the leukemic progenitors. In some patients, the involved stem cells manifest pluripotent differentiative expression, whereas in others, the involved progenitors manifest differentiative expression mainly restricted to the granulocytic pathway. This is in contrast to chronic myelogenous leukemia (CML) which is a clonal disease known to arise in a pluripotent stem cell. Therefore, we tested whether these leukemias could be distinguished with respect to their involvement of immature precursors by studying colony-forming cells (CFC) and their precursors from four glucose-6-phosphate dehydrogenase (G6PD) heterozygous patients with AML and five patients with CML. CFC were separated from their precursors by FACS for expression of CD33 and CD34 followed by growth in a long-term culture (LTC) system. The vast majority of CFC express both the CD33 and CD34 antigens, but their less mature precursors, detected by their ability to give rise to CFC in LTC, express only CD34. In three of the four patients with AML, the CD33-CD34+ cells produced CFC in LTC that appeared to be predominantly or completely normal (ie, nonclonal) in origin. In the fourth patient, a significant enrichment of nonclonal progenitors was obtained in the CD33-CD34+ population, but these cells may also have included significant numbers of clonal cells. In contrast, in four of five patients with CML, cultures of both the CD33-CD34+ and CD33+CD34+ populations produced CFC in LTC that were almost entirely clonal in origin, whereas in the fifth patient a substantial number originated from nonclonal stem cells. These data indicate that granulocyte/monocyte progenitors are predominantly clonally derived in CML and AML. In CML, their precursors are also predominantly clonal, but in some cases of AML they are not. These findings may have implications for understanding the success or failure of current therapies of AML and CML.
急性髓系白血病（AML）是一种克隆性疾病，白血病祖细胞的分化表达模式具有异质性。在一些患者中，受累干细胞表现出多能分化表达，而在另一些患者中，受累祖细胞的分化表达主要局限于粒细胞途径。这与慢性髓系白血病（CML）形成对比，后者是一种已知起源于多能干细胞的克隆性疾病。因此，我们通过研究来自4例葡萄糖-6-磷酸脱氢酶（G6PD）杂合的AML患者和5例CML患者的集落形成细胞（CFC）及其前体细胞，来测试这些白血病是否可以根据其对未成熟前体细胞的累及情况加以区分。通过荧光激活细胞分选术（FACS）根据CD33和CD34的表达情况将CFC与其前体细胞分离，随后在长期培养（LTC）系统中培养。绝大多数CFC同时表达CD33和CD34抗原，但其不太成熟的前体细胞，通过其在LTC中产生CFC的能力检测到，仅表达CD34。在4例AML患者中的3例中，CD33-CD34+细胞在LTC中产生的CFC似乎主要或完全起源于正常（即非克隆性）细胞。在第4例患者中，CD33-CD34+群体中获得了显著富集的非克隆祖细胞，但这些细胞可能也包含大量克隆性细胞。相比之下，在5例CML患者中的4例中，CD33-CD34+和CD33+CD34+群体的培养物在LTC中产生的CFC几乎完全起源于克隆性细胞，而在第5例患者中，相当数量的CFC起源于非克隆性干细胞。这些数据表明，粒细胞/单核细胞祖细胞在CML和AML中主要来源于克隆。在CML中，它们的前体细胞也主要是克隆性的，但在某些AML病例中并非如此。这些发现可能对理解当前AML和CML治疗的成败具有启示意义。
