Malignant myeloblastic transformation of murine long-term bone marrow cultures by F-MuLV:In vitro reproduction of a long-term leukemogenesis, and investigation of preleukemic events

Abstract

A Friend helper virus I⁻⁵(F-MuLV) which induces my-eloblastic leukemias in mice after a latency of several months, was used to infect long-term bone marrow cultures. From 48 to 71 weeks after in vitro infection, 4/14 cultures gave rise to transplantable malignant myeloblas-tic cells. These cells were shown to genuinely result from an in vitro transformation of virus-infected normal bone marrow cells. The in vitro transformation reproduced the course of the in vivo disease. It provided unique material for in vitro investigation of the preleukemic stages of long-term leukemogenesis. Successive cellular events were: (I) freezing of the normal myelomonocytic differentiation process; (2) change from factor-dependent to an autonomous growth; (3) acquisition of in vivo tumorigenicity.