Vosika G J, Krivit W, Gerrard J M, Coccia P F, Nesbit M E, Coalson J J, Kennedy B J
Proc Natl Acad Sci U S A. 1975 Jul;72(7):2804-8. doi: 10.1073/pnas.72.7.2804.
Particles with the density and enzymatic activity characteristic of known oncornavirus have been previously described in bone marrow cells from patients with leukemia in relapse and in remission. We have confirmed these findings and studied two patients in whom preleukemia was among the diagnostic considerations. Following cultivation of bone marrow from these patients for 1 week in conditioned media with dexamethasone, a high-speed pellet of the supernatant fluid and disrupted cells was prepared and analyzed on a sucrose gradient for enzymatic activity characteristic of RNA-directed DNA polymerase (reverse transcriptase). Peaks of endogenous DNA polymerase activity showing ribonuclease sensitivity and/or stimulation with the synthetic template poly(rC)-(dG)12-18 were demonstrated in both patients at densities of 1.15 to 1.19 and 1.21 to 1.24 g/ml. Subsequently, diagnosis 2 and 4 months after initial evaluation revealed acute myelogenous leukemia and malignant histiocytosis, respectively. Prior studies have suggested a possible etiological significance of such particles in human leukemia. The demonstration of similar particles preceding clinically overt disease in these patients supports this hypothesis and offers the possibility of early diagnosis and treatment.
先前已在复发和缓解期白血病患者的骨髓细胞中描述过具有已知肿瘤病毒特征的密度和酶活性的颗粒。我们证实了这些发现，并研究了两名诊断时考虑有白血病前期的患者。在含有地塞米松的条件培养基中将这些患者的骨髓培养1周后，制备了上清液和破碎细胞的高速沉淀，并在蔗糖梯度上分析其是否具有RNA指导的DNA聚合酶（逆转录酶）的酶活性特征。在两名患者中，均在密度为1.15至1.19 g/ml和1.21至1.24 g/ml处显示出对内切核糖核酸酶敏感和/或受合成模板聚（rC）-（dG）12-18刺激的内源性DNA聚合酶活性峰。随后，在初次评估后2个月和4个月的诊断分别显示为急性髓性白血病和恶性组织细胞增多症。先前的研究表明此类颗粒在人类白血病中可能具有病因学意义。在这些患者中，在临床明显疾病出现之前就发现了类似颗粒，这支持了这一假说，并提供了早期诊断和治疗的可能性。
