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Multistep virus-induced leukemogenesis in vitro: description of a model specifying three steps within the
Abstract:
A helper-independent Friend leukemia virus was used to infect bone marrow cultures. This virus induces myeloblastic leukemia in mice after a long latency period. Infection of the bone marrow cultures resulted in the in vitro production of myeloblastic leukemogenesis after a long latency period. Three steps were observed in the evolution of the infected cultures, and permanent cell lines were derived at each step. This allowed us to individualize three successive events in the course of the myeloblastic transformation: (i) an abnormal responsiveness to the physiological hormone granulo-macrophagic colony-stimulating factor, (ii) the acquisition of growth autonomy, and (iii) the acquisition of in vivo tumorigenicity.
Insights
Friend leukemia virus infection of bone marrow cultures led to myeloblastic leukemia in mice. The study identified three key steps in leukemogenesis: altered hormone response, growth autonomy, and tumor formation.
Area of Science:
- * Molecular biology
- * Cancer research
- * Virology
Background:
- * Friend leukemia virus (FLV) is known to induce leukemia in mice.
- * Understanding the early events in viral leukemogenesis is crucial for developing targeted therapies.
Purpose of the Study:
- * To investigate the in vitro transformation of bone marrow cells by FLV.
- * To identify the sequential events leading to myeloblastic leukemia.
Main Methods:
- * Infection of mouse bone marrow cultures with a helper-independent FLV.
- * Establishment of permanent cell lines at successive stages of transformation.
- * Analysis of cellular responses to growth factors and tumorigenicity.
Main Results:
- * FLV infection induced myeloblastic leukemogenesis in vitro after a prolonged latency.
- * Three distinct stages of transformation were observed: abnormal granulo-macrophagic colony-stimulating factor (GM-CSF) responsiveness, acquisition of growth autonomy, and development of in vivo tumorigenicity.
- * Permanent cell lines were derived at each stage, facilitating detailed analysis.
Conclusions:
- * Myeloblastic transformation by FLV is a multi-step process.
- * Altered GM-CSF signaling and growth autonomy are critical early events in leukemogenesis.
- * The derived cell lines provide valuable models for studying leukemia development and progression.