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[Colonization of the mouse liver by transplanted virogenic leukemia cells. Electron microscopic investigations
Abstract:
Cells of a virogenic, immature myelogenic leukemia were injected in i.p. in one week old mice, strain NMRI, each animal receiving 10(5), 10(6) or 13(7) cells respectively in 0.2 ml Hanks' BSS. Mice were sacrificed at different times between 10 hrs and 21 days p.i. and liver specimens were prepared for electronmicroscopic studies. 10 hrs p.i. the leukemic cells are found in the sinusoids of the liver and after 30 hrs in the periportal fields. The leukemia cells migrate into the Disse spaces from the sinusoids. The leukemic cells penetrate with cytoplasmic digitations between connected endothelial cells. There is no lytic disintegration of the endothelial cells. The leukemic cells multiply by mitotic division of the Disse spaces, thereby compressing the liver cells. The cell membranes of both cell-types remain intact. Electronmicroscopically no evidence is found of a secretion of enzymes from the leukemia cells that destroy liver cells. Destruction of the liver cells is the consequence of the growth-pressure exerted by the dividing leukemic cells. Within the liver of the recipients the leukemic cells produce RNA-viruses. In the cytoplasm - frequently in the area of the Golgi-field - groups of immature A-particles are formed. In the virus fields the ribosomes disappear. The immature A-particles consist of two concentric electron dense shells. On the surface of the liver cells budding particles and immature C-particles develop. Extracellular mature C-particles with a homogeneous nucleoid and an irregular outer shell may be seen. The formation of viruses is found to be independent of the stage of the leukemia.
Insights
Immature myelogenic leukemia cells injected into mice infiltrate liver sinusoids and Disse spaces, causing liver cell destruction through growth pressure, not enzymatic action. These leukemia cells also produce RNA-viruses within the liver.
Area of Science:
- * Virology and Cancer Biology: Investigating the pathogenesis of virogenic, immature myelogenic leukemia and its interaction with host liver cells.
- * Electron Microscopy: Utilizing high-resolution imaging to elucidate cellular and subcellular events during leukemia progression and viral replication.
Context:
- * Leukemia is a cancer of blood-forming tissues, including bone marrow and the lymphatic system.
- * Virogenic and immature myelogenic leukemia subtypes present unique challenges in understanding disease mechanisms and progression.
Purpose:
- * To investigate the cellular mechanisms by which immature myelogenic leukemia cells infiltrate and damage mouse liver tissue.
- * To identify the role of RNA-virus production by leukemia cells within the liver microenvironment.
- * To characterize the ultrastructural changes in liver cells and leukemia cells during the disease process.
Summary:
- * Leukemia cells were injected into young mice, and liver tissues were examined via electron microscopy at various time points.
- * Leukemia cells were observed to migrate into Disse spaces, multiply via mitotic division, and compress surrounding liver cells, leading to destruction.
- * RNA-viruses, including immature A-particles and budding C-particles, were identified within the cytoplasm of leukemia cells and on the surface of liver cells.
Impact:
- * This study reveals that liver cell destruction in this leukemia model is primarily due to physical pressure from multiplying leukemia cells, not enzymatic degradation.
- * The findings highlight the potential for RNA-virus production by leukemia cells within the liver, offering insights into viral oncogenesis.
- * Understanding these cellular and viral dynamics is crucial for developing targeted therapies for specific leukemia subtypes.