Modulation of the haemopoietic system by murine retroviruses

Abstract

Infection with different retrovirus isolates of cells from the blood-forming system of the mouse can lead to qualitative or quantitative changes in the pluripotent stem cell and committed progenitor cell compartment. At the present time, the molecular and cellular basis for these changes is not understood. This incomplete picture is largely due to our lack of knowledge of both cellular haemopoiesis and the role of cellular oncogenes in normal haemopoietic differentiation. Thus, a number of questions remain to be answered. For example, does Abelson leukaemia virus induce B-cell tumours because the c-abl gene product, the normal counterpart of the v-abl transforming gene of Abelson virus, is normally not expressed in pre-B-cells? Or alternatively, as the c-abl gene a key regulatory gene in lymphopoiesis, and thus does the constitutive and unregulated expression of its gene product, such as occurs after Abelson virus infection, initiate the first steps to malignant transformation? Similarly, is the reduced requirement for, or complete autonomy from, haemopoietic cell growth factors, a secondary late event of leukaemic transformation or are the gene products of the retrovirus onc gene analogous or equivalent to these regulatory molecules? It seems evident that answers to these and other questions on the nature of leukaemic transformation by retroviruses will depend on further experimentation that combines cellular, molecular and virological approaches. Such studies will probably provide information not only on leukaemic transformation, but normal haemopoiesis as well.