Wustrow T P, Andreeff M, Fernandes G, Good R A
Leuk Res. 1985;9(10):1283-91. doi: 10.1016/0145-2126(85)90158-4.
The development of the leukemia-lymphoma complex was studied in AKR/J (H-2k) mice using flow cytometry and staining with acridine orange. Investigation of cytokinetics and of cellular RNA content showed that during the neonatal period all mice had a significant increase of S phase cells in the thymus, bone marrow, lymph nodes and spleen reflecting extramedullary hematopoiesis. Concomitantly, G0/G1 cells were significantly reduced in the thymus, lymph nodes and spleen when compared to 6-week old mice of the same strain. No changes in the cell cycle or in RNA content were observed until 10 months of age in congeneic AKR (H-2b) mice, which do not develop leukemia during the first year of life. In leukemia-prone AKR/J (H-2k) mice, however, it was shown that the first appearance of a leukemic process may be recognized in the thymus by a significant increase of cells in G1 phase of the cell cycle which have a high RNA content. These changes were first seen at 5 months of age before the increased expression of MuLV antigen signals preleukemic alterations at 6 months of age and long before morphological changes appear (8-10 months). Furthermore, at 6 months these mice showed a significant elevation of cells in S phase which always appeared initially in the thymus. By 10 months of age, when the mice were overtly leukemic, these changes had progressed in all lymphoid organs and in the peripheral blood. At the same time a unique population of cells was observed that was characterized by cells in S and G2M with very low RNA content. The method used is applicable to further analysis of the precise locus of development of leukemia in the thymus of AKR/J (H-2k) mice, analysis of the nature of the earliest malignant cells, and investigation of the influence of viruses in the pathogenesis of AKR leukemia.
利用流式细胞术和吖啶橙染色法，对AKR/J（H-2k）小鼠白血病-淋巴瘤复合体的发育进行了研究。细胞动力学和细胞RNA含量的研究表明，在新生期，所有小鼠的胸腺、骨髓、淋巴结和脾脏中S期细胞显著增加，这反映了髓外造血。与此同时，与同品系6周龄小鼠相比，胸腺、淋巴结和脾脏中的G0/G1期细胞显著减少。在同基因的AKR（H-2b）小鼠中，直到10月龄都未观察到细胞周期或RNA含量的变化，这些小鼠在出生后第一年不会发生白血病。然而，在易患白血病的AKR/J（H-2k）小鼠中，研究表明，白血病过程的首次出现可通过细胞周期G1期具有高RNA含量的细胞显著增加在胸腺中得以识别。这些变化在5月龄时首次出现，早于6月龄时MuLV抗原信号增加所预示的白血病前期改变，也远早于形态学变化出现（8-10月龄）。此外，在6月龄时，这些小鼠的S期细胞显著升高，且总是首先出现在胸腺中。到10月龄小鼠明显患白血病时，这些变化已在所有淋巴器官和外周血中进展。同时，观察到一个独特的细胞群体，其特征是S期和G2M期细胞的RNA含量非常低。所使用的方法适用于进一步分析AKR/J（H-2k）小鼠胸腺中白血病发育的确切位点、最早恶性细胞的性质以及病毒在AKR白血病发病机制中的影响。
