PRODUCTION OF MESENCHYMAL TUMORS IN NUDE-MICE BY PH1 NEGATIVE FIBROBLASTS OBTAINED FROM A PH1 POSITIVE CML PATIENT - PRELIMINARY-REPORT

  • 1 January 1978
    • journal article
    • research article
    • Vol. 6  (6) , 549-557
Abstract
An experimental model system is presented for the investigation in humans of the role of hematopoietic stromal elements in the regulation of hematopoiesis as well as in the pathogenesis of myelofibrosis in myeloproliferative disorders. The model is based on the simultaneous application of 3 experimental techniques: growth of bone marrow derived fibroblastic colonies in vitro, cytogenetic demonstration of marker chromosomes associated with hematopoietic malignancies and transplantation of isolated stromal elements into athymic (nude) mice. Using this model, the induction of mesenchymal tumors in nude mice by Ph1 negative fibroblasts obtained from the bone marrow of a patient with a Ph1 positive chronic myelogenous leukemia was described. Mesenchymal tumors were also induced in nude mice with bone marrow derived fibroblasts from a patient with aplastic anemia, who was successfully treated with bone marrow transplantation, and a normal human volunteer. Morphologic, cytogenetic and EM studies of bone marrow mesenchymal elements in culture and tumors induced in nude mice from the CML [chronic myelogenous leukemia] patient indicate the cells composing the tumor are of human origin and are negative for the Ph1 chromosome. The results provide the 1st in vivo morphological and cytogenetic support using human materials, of the hypothesized relationship of progenitors of in vitro fibroblastic colonies to marrow stromal elements.