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Detection of lymphoid leukemia colony-forming cells in Abelson virus infected mice: differences in inbred strains
Abstract:
BALB/c or DBA/2 mice were infected with Abelson murine leukemia virus (A-MuLV), pseudotype Molony murine leukemia virus (M-MuLV). Infection of these mice with 10(4) focus-forming units of A-MuLV(M-MuLV) induced overt leukemia, detectable grossly or microscopically in 90% of the mice at 20-38 days. However, these methods did not detect leukemia at 17 days or before. Bone marrow cells from A-MuLV-infected leukemic or preleukemic mice were placed in tissue culture in a soft agarose gel. Cells from leukemic or preleukemic BALB/c mice grew to form colonies of 10(3) cells or more, composed of lymphoblasts, whereas marrow cells from normal uninfected mice did not. Cells from these colonies grew to form ascitic tumors after intraperitoneal inoculation into pristane-primed BALB/c recipients. Colony-forming leukemia cells could be detected in the marrow of A-MuLV-infected mice as early as 8 days after virus inoculation. The number of colony-forming leukemia cells increased as a function of time after virus inoculation. Colony-forming leukemia cells require other cells in order to replicate in tissue culture. Normal bone marrow cells, untreated or after treatment with mitomycin-C, provide this "helper" function. Only in the presence of untreated or mitomycin-C treated helper cells was the number of colonies approximately proportional to the number of leukemia cells plated. Marrow cells from leukemic BALB/c mice form more colonies than those from leukemic DBA/2 mice. The number of colonies formed per 10(3) microscopically identifiable leukemia cells plated was determined to be 2-3 for leukemic BALB/c mice and 0.3 for DBA/2 mice. Cocultivation of leukemic DBA/2 marrow cells with mitomycin-C treated normal BALB/c cells did not increase the number of colonies formed by the DBA/2 leukemic cells. Thus, the decreased ability of DBA/2 leukemia cells to form colonies appears to be a property of the leukemia cell population.
Insights
Researchers identified colony-forming leukemia cells in mice infected with Abelson murine leukemia virus (A-MuLV). These cells were detectable in bone marrow earlier than gross or microscopic leukemia detection, offering a sensitive method for early leukemia diagnosis.
Area of Science:
- * Hematology
- * Oncology
- * Virology
Background:
- * Abelson murine leukemia virus (A-MuLV) infection in BALB/c or DBA/2 mice induces leukemia.
- * Traditional detection methods (gross or microscopic) identify leukemia between 20-38 days post-infection.
Purpose of the Study:
- * To identify an earlier method for detecting leukemia induced by A-MuLV.
- * To characterize the properties of leukemia-inducing cells in vitro.
Main Methods:
- * Infection of mice with A-MuLV (M-MuLV pseudotype).
- * Culturing bone marrow cells in soft agarose to assess colony formation.
- * Assessing tumor formation after inoculation of cultured cells into recipient mice.
- * Evaluating the requirement of helper cells for leukemia cell replication.
Main Results:
- * Colony-forming leukemia cells (lymphoblasts) were detected in bone marrow of infected mice as early as 8 days post-inoculation.
- * Colony formation was dependent on the presence of normal bone marrow helper cells.
- * BALB/c mice exhibited a higher colony-forming capacity compared to DBA/2 mice, indicating a cell-intrinsic property.
Conclusions:
- * Colony-forming leukemia cells provide an early marker for A-MuLV-induced leukemia.
- * The reduced colony-forming ability in DBA/2 mice is a characteristic of the leukemia cells themselves.
- * This assay offers a sensitive method for studying leukemia development and potentially therapeutic interventions.